Iman Hewedi - Academia.edu (original) (raw)

Papers by Iman Hewedi

Research paper thumbnail of Prune 2 immunohistochemical expression in uterine smooth muscle tumors

The histologic classification of uterine smooth muscle tumors regarding their malignant potential... more The histologic classification of uterine smooth muscle tumors regarding their malignant potential is often challenging dilemma. Prune 2 has been reported to have a diagnostic utility in differentiating leiomyosarcomas from gastrointestinal stromal tumors. However, its diagnostic value in leiomyosarcoma versus other uterine smooth muscle tumors has not been elucidated yet. The aim of this study was to assess the value of Prune 2 immunohistochemical expression in distinguishing uterine smooth muscle tumors including leiomyomas (LM), Leiomyomas with bizarre nuclei (LBN), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMS) and to investigate its prognostic role in LMS. Immunohistochemical expression of Prune 2 was investigated in 94 uterine smooth muscle tumors including; 38 LM, 12 LBN, 6 STUMP and 38 LMS. Prune 2 immunostaining was scored based on the extent and intensity of staining. All 94 uterine smooth muscle tumors showed at least focal weak Pr...

Research paper thumbnail of Clinicopathologic significance of molecular classification of breast cancer: relation to nottingham prognosis index

PURPOSE The aim of this work is to determine the possible relationship between the different prof... more PURPOSE The aim of this work is to determine the possible relationship between the different profiles of molecular expression of hormone receptors and Her-2÷neu receptors to clinical and histopathological known prognostic variables for breast cancer. MATERIALS AND METHODS A total of 110 breast carcinoma tumor samples were included. In this study 4 groups or immunohistochemical profiles were defined, based on expression of hormone receptors (estrogen and÷or progesterone) and÷or Her2÷neu (Luminal A, Luminal B, HER2 overexpressing profile, and triple-negative profile). We studied whether there were differences between them regarding clinical and histopathological variables with a known prognostic significance in addition to Nottingham Prognosis Index (NPI). RESULTS In this series, 65 cases corresponded to Luminal A (59.1%), 18 cases (16.4%) were Luminal B, in 14 cases (12.7%) HER2 was over-expressed, while 13 cases (11.8%) were of the triple negative subtype. It is worth noting the rel...

Research paper thumbnail of Diagnostic Role Of Resistin In Nonalchoholic Fatty Liver Disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidit... more Introduction: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and mortality. Insulin resistance is believed to be a key factor in the development of fatty liver. Moreover, insulin resistance states characterized by elevated expression and production of several cytokines; of particular adiponectin, leptin, resistin. Leptin and adiponectin have been implicated in the pathogenesis and progression of NAFLD but direct evidence of the role of resistin in NAFLD is lacking. The aim of this study was to determine the circulating resistin level in patients affected by NAFLD and to correlate resistin level with insulin sensitivity, liver function and histological features. Subjects and methods: This study included 100 subjects divided into: Forty patients with NAFLD, forty obese persons with BMI >30 having normal transaminases and normal liver ultrasound, and twenty controls with BMI < 20. For all subjects serum resistin was measured, Homeostasis mode...

Research paper thumbnail of Immunohistochemical expression of HGF and cMET in meningiomas

QJM: An International Journal of Medicine

Background Meningiomas are the most common intracranial neoplasm together with gliomas; but unlik... more Background Meningiomas are the most common intracranial neoplasm together with gliomas; but unlike gliomas they are still graded according to their histopathological picture. Many growth factors and tyrosine kinase receptors have been studied in meningiomas in an attempt for prognostic stratification of patients, also to find a suitable targeted therapy for meningiomas. Aim of the study To correlate the immunohistochemical expression of HGF and cMET with the different WHO grades of meningioma in addition to brain invasion. Materials and methods This study included 60 cases of meningiomas (WHO grade I, n = 30 and WHO grade II & III, n = 30), brain invasion was present in 14 cases. Results HGF, cMET & HGF/cMET co-expression were positive in 60.0%, 65.0% and 58.3% respectively of the cases; WHO grade I meningioma showed positivity in 30.0%, 33.3% and 30.0% of the cases respectively in contrast with 90.0%, 96.7% and 86.7% of the cases of WHO grades II & III meningiomas respectively. The...

Research paper thumbnail of Diagnostic role of MUC4 immunohistochemical expression in various subtypes of meningioma

Egyptian Journal of Pathology

Background Meningiomas exhibit a wide range of histological appearances, and they may show overla... more Background Meningiomas exhibit a wide range of histological appearances, and they may show overlapping morphology with other nonmeningothelial tumors, and so the differential diagnosis may be challenging. Aim To examine the diagnostic role of MUC4 expression in various histological subtypes and grades of meningioma and some other nonmeningothelial tumors relevant to the potential diagnosis. Materials and methods The expression of MUC4 and epithelial membrane antigen was analyzed by immunohistochemical staining in various subtypes of meningiomas and other nonmeningothelial tumors that enter in the differential diagnosis (schwannoma, solitary fibrous tumors/hemangiopericytoma, glioblastoma, and hemangioblastoma). Results A statistically significant difference was detected between MUC4 expression in meningioma and other nonmeningothelial tumors (P<0.001). MUC4 was expressed in 83.3% of meningioma cases and was entirely negative in nonmeningothelial tumors, with 83.3% sensitivity and 100% specificity. Conclusion MUC4 is a possible novel adjunct diagnostic marker that can distinguish between confusing cases of meningioma and the tested nonmeningothelial tumors.

Research paper thumbnail of Folate receptor-α expression in triple-negative and non-triple-negative invasive breast carcinoma

Egyptian Journal of Pathology

Background and objective Breast cancer is a heterogeneous disease with variable behavior and resp... more Background and objective Breast cancer is a heterogeneous disease with variable behavior and response to therapy. It is grouped into three main molecular subtypes: estrogen receptor and/or progesterone receptor expressing, human epidermal growth factor receptor-2 expressing, or triple-negative breast cancer (TNBC). There are currently no established targeted therapies for TNBC. The folate receptor-&agr; (FRA) is a glycosylphosphatidylinositol-linked protein overexpressed in certain malignancies, along with its low coordinate expression in normal tissue. Therefore, FRA is an attractive target for directed therapies. The aim of this study was to assess immunohistochemical expression of FRA in invasive breast carcinomas and to explore its association with TNBC and non-triple-negative breast cancer (NTNBC), trying to specify the subset of patients with breast cancer who might benefit most from anti-folate receptors targeted therapy. Materials and methods This retrospective study was conducted on 60 invasive breast carcinoma tissue samples: 30 cases of TNBC cases and 30 cases of NTNBC. All were retrieved from archives of the Pathology Laboratory of Ain Shams Specialized Hospital. Immunohistochemistry using rabbit polyclonal anti-FRA antibody was performed to detect the expression of FRA, which was subsequently correlated with different pathological parameters. Results Statistically significant higher expression of FRA was noted in TNBC group in comparison with NTNBC group (P=0.02). On the contrary, no significant correlation was found between FRA expression and tumor size, tumor type, tumor grade, or lymph node status. Conclusion FRA expression is strongly associated with TNBC cases, and such association suggests its potential role in tumorigenesis. As such, novel premises for treatment of TNBC are anticipated by targeting its molecule.

Research paper thumbnail of Frequency of primary central nervous system tumors in a tertiary hospital, Cairo, Egypt

The Journal of Community Health Management

Introduction: In Egypt, few epidemiologic reports have highlighted the national and regional epid... more Introduction: In Egypt, few epidemiologic reports have highlighted the national and regional epidemiologic data regarding primary CNS tumors. In this study we aim to identify the frequency of various primary CNS tumors and to demonstrate the age group distribution, gender, topographic data and the different histopathologic types among our patients. Materials and Methods: Data on all cases of primary CNS neoplasms received at Pathology department of Ain Shams University Specialized hospital in addition to a referral neuropathology lab during the period from 2010 to 2015 were collected with a total number of 996 cases. The patients were divided according to their age into two main groups, pediatric group including children and adolescents (from 0-18 years), and adult group (> 18 years). Patients' demographic data and histopathologic tumor types were analyzed. Result: Frequency of primary CNS tumors among males was higher than females (51.7% vs. 49.3% respectively). Regarding patient age, frequency among adults was (89.4%) compared to pediatric age group (10.6%). Gliomas were the most common primary CNS tumors in adults (35%) followed by meningiomas (33.3%) then pituitary adenomas (15.6%); while in pediatric group embryonal tumors (17%) were the second most common following gliomas (59.4%). Conclusion: This study highlighted the frequency, spectrum and prominent features of primary CNS tumors among Egyptian patients, in comparison to many worldwide reports. This study recommends the establishment of specialized national center for CNS tumors in Egypt; this will provide efficient registry system and accurate data analysis for these tumors.

Research paper thumbnail of Prolapsed lumbar disc in a nine years old girl: a case report

Egyptian Journal of Neurosurgery

Lumbar disc prolapse has been rarely described in young children. In this report, we reported a l... more Lumbar disc prolapse has been rarely described in young children. In this report, we reported a lumbar disc prolapse in an overweight 9-year-old girl after trauma. The girl had a severe radicular pain that did not respond to conservative treatment. Operative management was conducted, and histopathologic examination of the prolapsed disc material revealed chondrocyte proliferation, tears and clefts of the annulus fibrosus, and fibrocartilaginous degeneration. These early degenerative changes suggested the effect of the high body mass index as an underlying factor for the disc prolapse in this girl.

Research paper thumbnail of Endoscopic Extracapsular Resection of Pituitary Adenoma in Cushing’s Disease: A Myth or a Reality?

29th Annual Meeting North American Skull Base Society

Research paper thumbnail of Corrigendum to: Genetic underpinnings in Alzheimer's disease - a review

Reviews in the neurosciences, Sep 4, 2018

In the author list of the above article the name of Joman Y. Natsheh was inadvertently misspelled... more In the author list of the above article the name of Joman Y. Natsheh was inadvertently misspelled as "Joman Y. Natesh". In the following the author list with the correct spelling of J.Y. Natsheh's name is given:

Research paper thumbnail of A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle

Nature communications, Feb 23, 2018

Chordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina... more Chordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina terminalis along the anterior wall of the third ventricle. Despite being histologically low-grade, chordoid gliomas are often associated with poor outcome, as their stereotypic location in the third ventricle makes resection challenging and efficacious adjuvant therapies have not been developed. Here we performed genomic profiling on 13 chordoid gliomas and identified a recurrent D463H missense mutation in PRKCA in all tumors, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCα). Expression of mutant PRKCA in immortalized human astrocytes led to increased phospho-ERK and anchorage-independent growth that could be blocked by MEK inhibition. These studies define PRKCA as a recurrently mutated oncogene in human cancer and identify a potential therapeutic vulnerability in this uncommon brain tumor.

Research paper thumbnail of Genetic underpinnings in Alzheimer’s disease – a review

Reviews in the Neurosciences

In this review, we discuss the genetic etiologies of Alzheimer’s disease (AD). Furthermore, we re... more In this review, we discuss the genetic etiologies of Alzheimer’s disease (AD). Furthermore, we review genetic links to protein signaling pathways as novel pharmacological targets to treat AD. Moreover, we also discuss the clumps of AD-m ediated genes according to their single nucleotide polymorphism mutations. Rigorous data mining approaches justified the significant role of genes in AD prevalence. Pedigree analysis and twin studies suggest that genetic components are part of the etiology, rather than only being risk factors for AD. The first autosomal dominant mutation in the amyloid precursor protein (

Research paper thumbnail of CD24 expression in retinoblastoma

Egyptian Journal of Pathology

Background Retinoblastoma is an aggressive eye cancer of infancy and childhood. Identification of... more Background Retinoblastoma is an aggressive eye cancer of infancy and childhood. Identification of high-risk features for tumor spread and a possible prognostic marker during histopathological examination of enucleated eyes is crucial to guard further treatment and follow-up plan. CD24 is reported as a poor prognostic marker in many types of malignant tumors. Objective The aim of the present study was to evaluate CD24 immunohistochemical expression in retinoblastoma and its correlation with clinicopathological features, to explore the possible prognostic value of CD24 in these tumors. Materials and methods This retrospective study included 33, formalin-fixed, paraffin-embedded tissue sections from primarily enucleated eyes with retinoblastoma. Immunohistochemical staining for CD24 was performed. The staining pattern was recorded, and both extent and intensity of staining were evaluated semiquantitatively. An additive score (AS) for CD24 expression was calculated for each tumor. CD24 expression was subsequently correlated with various clinicopathological features. Results At least focal, weak CD24 staining was noted in all studied cases of retinoblastomas. The staining pattern was membranous-cytoplasmic in 60.6% of cases and membranous in the remaining 39.4%. In differentiated areas of tumors, Homer–Wright rosettes were found to have no CD24 expression, whereas Flexner–Wintersteiner rosettes showed variable apical staining. CD24 staining intensity and extent were significantly related to retinoblastoma risk groups with more strong and diffuse CD24 expression among high-risk retinoblastomas compared with low-risk tumors (P=0.033 and 0.048, respectively). The extraocular retinoblastomas demonstrated more diffuse CD24 staining compared with the intraocular tumors (P=0.029). Conclusion CD24 is overexpressed in retinoblastoma, and immunohistochemically determined CD24 expression is a potential marker of prognosis in this disease.

Research paper thumbnail of Diagnostic value of the combined use of SATB2 and CDX2 in mucinous carcinoma of colorectal origin

Egyptian Journal of Pathology

Background Metastatic mucinous adenocarcinoma from an unknown primary site is a frequent clinical... more Background Metastatic mucinous adenocarcinoma from an unknown primary site is a frequent clinical dilemma. The ability to confirm or exclude a diagnosis of carcinoma of colorectal origin by immunohistochemistry has been limited by the lack of a reliable positive marker for colorectal differentiation. Caudal type homeobox 2 (CDX2) has been reported to be expressed in intestinal adenocarcinomas; yet, it is also expressed in other tumors such as those of the pancreas, bile ducts, bladder, endometrium, and ovary. Special AT-rich sequence-binding protein 2 (SATB2) has been recently linked to colorectal cancer. The diagnostic role of SATB2 in mucinous carcinoma of colorectal origin has not been previously elaborated. Aim The aim of this study was to investigate the diagnostic value of SATB2 in differentiating mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins as compared with that of CDX2. Materials and methods A comparative immunohistochemical study of SATB2 and CDX2 expression was performed in 42 cases of primary mucinous carcinomas (colorectal=10, breast=14, cervix=10, stomach=8) and 22 cases of metastatic mucinous colorectal carcinoma. The predictive capacity of SATB2 and CDX2 expression for diagnosing the mucinous carcinoma of colorectal origin was determined individually and in combination using sensitivity, specificity, and positive and negative predictive value calculations. Results SATB2 demonstrated positive immunoreactivity in all cases of primary colorectal carcinoma and 81.8% of metastatic colorectal carcinomas in addition to 57.1% of breast, 40% of cervical, and 25% of gastric tumors. CDX2 was positively expressed in 60% of primary colorectal carcinomas and 72.7% of metasty tatic colorectal carcinomas, but it was negative in all noncolonic primary mucinous carcinomas. The SATB2 expression showed a sensitivity of 100% and a specificity of 56.2% in identifying colorectal origin of mucinous carcinomas, compared with 60 and 100% for CDX2 expression, respectively. The combined use of both SATB2 and CDX2 raised both the sensitivity and the negative predictive values to 100% if any of the two markers showed positivity as compared with the isolated use of CDX2. Conclusion SATB2 is a more sensitive yet less specific marker for diagnosis of mucinous carcinoma of colorectal origin as compared with CDX2. SATB2 in combination with CDX2 increases the accuracy of distinguishing mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins; therefore, SATB2 is considered a useful marker in this respect.

Research paper thumbnail of Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression

Applied immunohistochemistry & molecular morphology : AIMM, Jan 30, 2017

Loss in apoptosis competence often results in augmented genomic instability contributing to carci... more Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0...

Research paper thumbnail of Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency

Folia Neuropathologica, 2017

Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the c... more Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the cerebrospinal venous outflow routes, which is postulated to cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to iron deposition which triggers inflammation and demyelination in MS. Invasive endovascular treatment of CCSVI was initiated based on the previous theory. The present study was designed to validate this hypothesis using a rat model of CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats (n = 15), and sham-operated rats (n = 15) were used as a control group. The rats were followed clinically for eight months and neurological examination detected no weakness or paralysis in the operated rats. At the end of the experiment, the rats were sacrificed and the brains were processed for histopathological examination of tissue sections stained by hematoxylin and eosin, myelin stain, silver impregnation, iron stain and immunohistochemical preparations for GFAP, CD68 and CD45. Semithin sections stained with toluidine blue were also examined. In the JVL group, increased iron deposition in the white matter was detected. An increase in the size and number of astrocytes along with increased GFAP immunoreactivity denoting reactive gliosis was also noted in the JVL group. However, no signs of demyelination, inflammation or axonopathy were detected. This study revealed that iron deposition in the JVL group as a model for CCSVI was not associated with cardinal histopathological findings of MS. It is therefore recommended that the invasive endovascular treatment of CCSVI should be reconsidered and further controlled clinical studies be carried out to provide a better understanding of the pathogeneses of MS.

Research paper thumbnail of Immunohistochemical expression of survivin in breast carcinoma: relationship with clinicopathological parameters, proliferation and molecular classification

Journal of the Egyptian National Cancer Institute

Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with... more Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinicopathological parameters, proliferation (MIB-1) and molecular classification Our retrospective study comprised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immunostained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immunonegative. Survivin expression showed significant association with increased tumor size (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), high histologic grade (p=0.04), lymph node metastases (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), advanced tumor stage (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), MIB-1 expression (p=0.02), negative estrogen receptor status (p=0.01) and negative progesterone receptor status (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes (p=0.01). Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel cancer treatment. Breast carcinoma - Immunohistochemistry - MIB-1 - Molecular classification - Survivin.

Research paper thumbnail of Diagnostic value of progesterone receptor and p53 expression in uterine smooth muscle tumors

Diagnostic Pathology, 2012

Background: The diagnosis of uterine smooth muscle tumors depends on a combination of microscopic... more Background: The diagnosis of uterine smooth muscle tumors depends on a combination of microscopic features. However, a small number of these tumors still pose difficult diagnostic challenges. Aim: To investigate progesterone receptor (PR) and p53 expression in leiomyomas (LMs), atypical leiomyomas (ALMs), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMSs) and to evaluate the potential utility of the selected immunohistochemical markers in differentiating these tumors. Materials and methods: Immunohistochemical expression of PR and p53 was investigated in 41 uterine smooth muscle tumors comprising: 15 LMS, 4 STUMP, 6 ALM and 16 LM. Quantitative evaluation of PR and p53 expression was graded on a scale from 0 to 3+. Results: Leiomyosarcomas showed reduced PR expression. All LMs as well as ALMs and STUMP were stained intensely for PR. Conversely, LMS was strongly stained with p53, while the three non-sarcomatous groups (STUMP, ALM, LM) were either entirely negative or weakly stained for p53. Regarding both PR and p53 expression, the difference between the LMS group and the three non-sarcomatous groups was highly significant (p < 0.001). Combined high PR-low p53 expression was seen in all the 26 examined cases of the non-sarcomatous group including the STUMP cases and none of the LMS cases. Therefore, it represents a "benign" profile with 100% specificity in diagnosis of a non-sarcomatous tumor. Conclusion: Immunohistochemistry for PR and p53 is valuable as an adjunct tool to morphological assessment of problematic uterine smooth muscle tumors.

Research paper thumbnail of Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27/Kip1 labeling indices

Journal of the Egyptian National …, 2011

Background: Pituitary tumors are a common form of endocrine neoplasia. However few studies assess... more Background: Pituitary tumors are a common form of endocrine neoplasia. However few studies assessed the expression of the principal cyclin regulating checkpoint exit, cyclin D1. Cyclin D1 expression in pituitary tumors and its possible relation to MIB-1 and p27/Kip1 labeling indices (LIs) was explored. Design: We studied a total of 199 pituitaries, including normal pituitaries (n = 7), pituitary adenomas (n = 187), and pituitary carcinoma (n = 5). All tissues were tested as cores of archived tissue microarrays that were immunostained for cyclin D1, MIB-1 and p27 using a standard technique. Tissue cores were subjected to automated analysis to evaluate the staining LIs. Results: No cyclin D1 positive cells in the normal anterior pituitary gland was found. Sparse nuclear staining was noted in pituitary tumors. Higher expression of cyclin D1 was noted in pituitary carcinomas compared to adenomas (p < 0.001), in non-functioning adenomas compared to functioning ones (p < 0.001) in macroadenomas versus microadenomas (p = 0.017) and in recurrent non recurrent adenomas (p < 0.001). Cyclin D1 LI and MIB-1 LI were related among adenomas (p < 0.001) and carcinomas (p = 0.041). p27 LI was neither related to pituitary adenoma recurrence nor invasion. Conclusions: Expression of cyclin D1 in pituitary tumors is related to cell proliferation, recurrence, and metastatic potential. Nuclear cyclin D1 expression is a good marker of aggressive behavior in pituitary tumors.

Research paper thumbnail of Perspectives on the immunologic microenvironment of astrocytomas

Cancer Management and Research, 2013

Background: The microenvironment of astrocytomas includes infiltrative inflammatory cells that ar... more Background: The microenvironment of astrocytomas includes infiltrative inflammatory cells that are dynamic in nature, possibly reflecting tumor biology. We evaluated the inflammatory cell infiltrate in astrocytic tumors aiming for a better understanding of their immunobiology. Methods: Immunohistochemical expression of CD68, CD3, and CD20 was investigated in 21 glioblastomas, 21 anaplastic astrocytomas, 13 diffuse astrocytomas, and 18 pilocytic astrocytomas. The inflammatory infiltrate was classified based on microanatomic location as perivascular and intratumoral, and subsequently graded semiquantitatively. Results: Perivascularly, CD68-positive infiltrate was noted in 71.4% of glioblastomas compared with 14.3% of anaplastic astrocytomas (P = 0.0001), 7.7% of diffuse astrocytomas (P = 0.0001), and 33.3% of pilocytic astrocytomas (P = 0.017). Intratumorally, 85.7% of glioblastomas exhibited CD68-positive infiltrate compared with 42.9% of anaplastic astrocytomas (P = 0.004), 38.5% of diffuse astrocytomas (P = 0.008), and 33.3% of pilocytic astrocytomas (P = 0.001). Among diffusely infiltrating astrocytomas, intratumoral CD3-positive infiltrate was only associated with glioblastoma. A CD20-positive infiltrate was only detected in the perivascular space of a single case of diffuse astrocytoma. Conclusion: These data indicate a distinct immune profile in the glioblastoma microenvironment primarily related to the prevalence of macrophages. Thus, novel glioblastoma therapies should address this key CD68-positive population and its possible role in generating an antitumor immune response.

Research paper thumbnail of Prune 2 immunohistochemical expression in uterine smooth muscle tumors

The histologic classification of uterine smooth muscle tumors regarding their malignant potential... more The histologic classification of uterine smooth muscle tumors regarding their malignant potential is often challenging dilemma. Prune 2 has been reported to have a diagnostic utility in differentiating leiomyosarcomas from gastrointestinal stromal tumors. However, its diagnostic value in leiomyosarcoma versus other uterine smooth muscle tumors has not been elucidated yet. The aim of this study was to assess the value of Prune 2 immunohistochemical expression in distinguishing uterine smooth muscle tumors including leiomyomas (LM), Leiomyomas with bizarre nuclei (LBN), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMS) and to investigate its prognostic role in LMS. Immunohistochemical expression of Prune 2 was investigated in 94 uterine smooth muscle tumors including; 38 LM, 12 LBN, 6 STUMP and 38 LMS. Prune 2 immunostaining was scored based on the extent and intensity of staining. All 94 uterine smooth muscle tumors showed at least focal weak Pr...

Research paper thumbnail of Clinicopathologic significance of molecular classification of breast cancer: relation to nottingham prognosis index

PURPOSE The aim of this work is to determine the possible relationship between the different prof... more PURPOSE The aim of this work is to determine the possible relationship between the different profiles of molecular expression of hormone receptors and Her-2÷neu receptors to clinical and histopathological known prognostic variables for breast cancer. MATERIALS AND METHODS A total of 110 breast carcinoma tumor samples were included. In this study 4 groups or immunohistochemical profiles were defined, based on expression of hormone receptors (estrogen and÷or progesterone) and÷or Her2÷neu (Luminal A, Luminal B, HER2 overexpressing profile, and triple-negative profile). We studied whether there were differences between them regarding clinical and histopathological variables with a known prognostic significance in addition to Nottingham Prognosis Index (NPI). RESULTS In this series, 65 cases corresponded to Luminal A (59.1%), 18 cases (16.4%) were Luminal B, in 14 cases (12.7%) HER2 was over-expressed, while 13 cases (11.8%) were of the triple negative subtype. It is worth noting the rel...

Research paper thumbnail of Diagnostic Role Of Resistin In Nonalchoholic Fatty Liver Disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidit... more Introduction: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and mortality. Insulin resistance is believed to be a key factor in the development of fatty liver. Moreover, insulin resistance states characterized by elevated expression and production of several cytokines; of particular adiponectin, leptin, resistin. Leptin and adiponectin have been implicated in the pathogenesis and progression of NAFLD but direct evidence of the role of resistin in NAFLD is lacking. The aim of this study was to determine the circulating resistin level in patients affected by NAFLD and to correlate resistin level with insulin sensitivity, liver function and histological features. Subjects and methods: This study included 100 subjects divided into: Forty patients with NAFLD, forty obese persons with BMI >30 having normal transaminases and normal liver ultrasound, and twenty controls with BMI < 20. For all subjects serum resistin was measured, Homeostasis mode...

Research paper thumbnail of Immunohistochemical expression of HGF and cMET in meningiomas

QJM: An International Journal of Medicine

Background Meningiomas are the most common intracranial neoplasm together with gliomas; but unlik... more Background Meningiomas are the most common intracranial neoplasm together with gliomas; but unlike gliomas they are still graded according to their histopathological picture. Many growth factors and tyrosine kinase receptors have been studied in meningiomas in an attempt for prognostic stratification of patients, also to find a suitable targeted therapy for meningiomas. Aim of the study To correlate the immunohistochemical expression of HGF and cMET with the different WHO grades of meningioma in addition to brain invasion. Materials and methods This study included 60 cases of meningiomas (WHO grade I, n = 30 and WHO grade II & III, n = 30), brain invasion was present in 14 cases. Results HGF, cMET & HGF/cMET co-expression were positive in 60.0%, 65.0% and 58.3% respectively of the cases; WHO grade I meningioma showed positivity in 30.0%, 33.3% and 30.0% of the cases respectively in contrast with 90.0%, 96.7% and 86.7% of the cases of WHO grades II & III meningiomas respectively. The...

Research paper thumbnail of Diagnostic role of MUC4 immunohistochemical expression in various subtypes of meningioma

Egyptian Journal of Pathology

Background Meningiomas exhibit a wide range of histological appearances, and they may show overla... more Background Meningiomas exhibit a wide range of histological appearances, and they may show overlapping morphology with other nonmeningothelial tumors, and so the differential diagnosis may be challenging. Aim To examine the diagnostic role of MUC4 expression in various histological subtypes and grades of meningioma and some other nonmeningothelial tumors relevant to the potential diagnosis. Materials and methods The expression of MUC4 and epithelial membrane antigen was analyzed by immunohistochemical staining in various subtypes of meningiomas and other nonmeningothelial tumors that enter in the differential diagnosis (schwannoma, solitary fibrous tumors/hemangiopericytoma, glioblastoma, and hemangioblastoma). Results A statistically significant difference was detected between MUC4 expression in meningioma and other nonmeningothelial tumors (P<0.001). MUC4 was expressed in 83.3% of meningioma cases and was entirely negative in nonmeningothelial tumors, with 83.3% sensitivity and 100% specificity. Conclusion MUC4 is a possible novel adjunct diagnostic marker that can distinguish between confusing cases of meningioma and the tested nonmeningothelial tumors.

Research paper thumbnail of Folate receptor-α expression in triple-negative and non-triple-negative invasive breast carcinoma

Egyptian Journal of Pathology

Background and objective Breast cancer is a heterogeneous disease with variable behavior and resp... more Background and objective Breast cancer is a heterogeneous disease with variable behavior and response to therapy. It is grouped into three main molecular subtypes: estrogen receptor and/or progesterone receptor expressing, human epidermal growth factor receptor-2 expressing, or triple-negative breast cancer (TNBC). There are currently no established targeted therapies for TNBC. The folate receptor-&agr; (FRA) is a glycosylphosphatidylinositol-linked protein overexpressed in certain malignancies, along with its low coordinate expression in normal tissue. Therefore, FRA is an attractive target for directed therapies. The aim of this study was to assess immunohistochemical expression of FRA in invasive breast carcinomas and to explore its association with TNBC and non-triple-negative breast cancer (NTNBC), trying to specify the subset of patients with breast cancer who might benefit most from anti-folate receptors targeted therapy. Materials and methods This retrospective study was conducted on 60 invasive breast carcinoma tissue samples: 30 cases of TNBC cases and 30 cases of NTNBC. All were retrieved from archives of the Pathology Laboratory of Ain Shams Specialized Hospital. Immunohistochemistry using rabbit polyclonal anti-FRA antibody was performed to detect the expression of FRA, which was subsequently correlated with different pathological parameters. Results Statistically significant higher expression of FRA was noted in TNBC group in comparison with NTNBC group (P=0.02). On the contrary, no significant correlation was found between FRA expression and tumor size, tumor type, tumor grade, or lymph node status. Conclusion FRA expression is strongly associated with TNBC cases, and such association suggests its potential role in tumorigenesis. As such, novel premises for treatment of TNBC are anticipated by targeting its molecule.

Research paper thumbnail of Frequency of primary central nervous system tumors in a tertiary hospital, Cairo, Egypt

The Journal of Community Health Management

Introduction: In Egypt, few epidemiologic reports have highlighted the national and regional epid... more Introduction: In Egypt, few epidemiologic reports have highlighted the national and regional epidemiologic data regarding primary CNS tumors. In this study we aim to identify the frequency of various primary CNS tumors and to demonstrate the age group distribution, gender, topographic data and the different histopathologic types among our patients. Materials and Methods: Data on all cases of primary CNS neoplasms received at Pathology department of Ain Shams University Specialized hospital in addition to a referral neuropathology lab during the period from 2010 to 2015 were collected with a total number of 996 cases. The patients were divided according to their age into two main groups, pediatric group including children and adolescents (from 0-18 years), and adult group (> 18 years). Patients' demographic data and histopathologic tumor types were analyzed. Result: Frequency of primary CNS tumors among males was higher than females (51.7% vs. 49.3% respectively). Regarding patient age, frequency among adults was (89.4%) compared to pediatric age group (10.6%). Gliomas were the most common primary CNS tumors in adults (35%) followed by meningiomas (33.3%) then pituitary adenomas (15.6%); while in pediatric group embryonal tumors (17%) were the second most common following gliomas (59.4%). Conclusion: This study highlighted the frequency, spectrum and prominent features of primary CNS tumors among Egyptian patients, in comparison to many worldwide reports. This study recommends the establishment of specialized national center for CNS tumors in Egypt; this will provide efficient registry system and accurate data analysis for these tumors.

Research paper thumbnail of Prolapsed lumbar disc in a nine years old girl: a case report

Egyptian Journal of Neurosurgery

Lumbar disc prolapse has been rarely described in young children. In this report, we reported a l... more Lumbar disc prolapse has been rarely described in young children. In this report, we reported a lumbar disc prolapse in an overweight 9-year-old girl after trauma. The girl had a severe radicular pain that did not respond to conservative treatment. Operative management was conducted, and histopathologic examination of the prolapsed disc material revealed chondrocyte proliferation, tears and clefts of the annulus fibrosus, and fibrocartilaginous degeneration. These early degenerative changes suggested the effect of the high body mass index as an underlying factor for the disc prolapse in this girl.

Research paper thumbnail of Endoscopic Extracapsular Resection of Pituitary Adenoma in Cushing’s Disease: A Myth or a Reality?

29th Annual Meeting North American Skull Base Society

Research paper thumbnail of Corrigendum to: Genetic underpinnings in Alzheimer's disease - a review

Reviews in the neurosciences, Sep 4, 2018

In the author list of the above article the name of Joman Y. Natsheh was inadvertently misspelled... more In the author list of the above article the name of Joman Y. Natsheh was inadvertently misspelled as "Joman Y. Natesh". In the following the author list with the correct spelling of J.Y. Natsheh's name is given:

Research paper thumbnail of A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle

Nature communications, Feb 23, 2018

Chordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina... more Chordoid glioma is a rare brain tumor thought to arise from specialized glial cells of the lamina terminalis along the anterior wall of the third ventricle. Despite being histologically low-grade, chordoid gliomas are often associated with poor outcome, as their stereotypic location in the third ventricle makes resection challenging and efficacious adjuvant therapies have not been developed. Here we performed genomic profiling on 13 chordoid gliomas and identified a recurrent D463H missense mutation in PRKCA in all tumors, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCα). Expression of mutant PRKCA in immortalized human astrocytes led to increased phospho-ERK and anchorage-independent growth that could be blocked by MEK inhibition. These studies define PRKCA as a recurrently mutated oncogene in human cancer and identify a potential therapeutic vulnerability in this uncommon brain tumor.

Research paper thumbnail of Genetic underpinnings in Alzheimer’s disease – a review

Reviews in the Neurosciences

In this review, we discuss the genetic etiologies of Alzheimer’s disease (AD). Furthermore, we re... more In this review, we discuss the genetic etiologies of Alzheimer’s disease (AD). Furthermore, we review genetic links to protein signaling pathways as novel pharmacological targets to treat AD. Moreover, we also discuss the clumps of AD-m ediated genes according to their single nucleotide polymorphism mutations. Rigorous data mining approaches justified the significant role of genes in AD prevalence. Pedigree analysis and twin studies suggest that genetic components are part of the etiology, rather than only being risk factors for AD. The first autosomal dominant mutation in the amyloid precursor protein (

Research paper thumbnail of CD24 expression in retinoblastoma

Egyptian Journal of Pathology

Background Retinoblastoma is an aggressive eye cancer of infancy and childhood. Identification of... more Background Retinoblastoma is an aggressive eye cancer of infancy and childhood. Identification of high-risk features for tumor spread and a possible prognostic marker during histopathological examination of enucleated eyes is crucial to guard further treatment and follow-up plan. CD24 is reported as a poor prognostic marker in many types of malignant tumors. Objective The aim of the present study was to evaluate CD24 immunohistochemical expression in retinoblastoma and its correlation with clinicopathological features, to explore the possible prognostic value of CD24 in these tumors. Materials and methods This retrospective study included 33, formalin-fixed, paraffin-embedded tissue sections from primarily enucleated eyes with retinoblastoma. Immunohistochemical staining for CD24 was performed. The staining pattern was recorded, and both extent and intensity of staining were evaluated semiquantitatively. An additive score (AS) for CD24 expression was calculated for each tumor. CD24 expression was subsequently correlated with various clinicopathological features. Results At least focal, weak CD24 staining was noted in all studied cases of retinoblastomas. The staining pattern was membranous-cytoplasmic in 60.6% of cases and membranous in the remaining 39.4%. In differentiated areas of tumors, Homer–Wright rosettes were found to have no CD24 expression, whereas Flexner–Wintersteiner rosettes showed variable apical staining. CD24 staining intensity and extent were significantly related to retinoblastoma risk groups with more strong and diffuse CD24 expression among high-risk retinoblastomas compared with low-risk tumors (P=0.033 and 0.048, respectively). The extraocular retinoblastomas demonstrated more diffuse CD24 staining compared with the intraocular tumors (P=0.029). Conclusion CD24 is overexpressed in retinoblastoma, and immunohistochemically determined CD24 expression is a potential marker of prognosis in this disease.

Research paper thumbnail of Diagnostic value of the combined use of SATB2 and CDX2 in mucinous carcinoma of colorectal origin

Egyptian Journal of Pathology

Background Metastatic mucinous adenocarcinoma from an unknown primary site is a frequent clinical... more Background Metastatic mucinous adenocarcinoma from an unknown primary site is a frequent clinical dilemma. The ability to confirm or exclude a diagnosis of carcinoma of colorectal origin by immunohistochemistry has been limited by the lack of a reliable positive marker for colorectal differentiation. Caudal type homeobox 2 (CDX2) has been reported to be expressed in intestinal adenocarcinomas; yet, it is also expressed in other tumors such as those of the pancreas, bile ducts, bladder, endometrium, and ovary. Special AT-rich sequence-binding protein 2 (SATB2) has been recently linked to colorectal cancer. The diagnostic role of SATB2 in mucinous carcinoma of colorectal origin has not been previously elaborated. Aim The aim of this study was to investigate the diagnostic value of SATB2 in differentiating mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins as compared with that of CDX2. Materials and methods A comparative immunohistochemical study of SATB2 and CDX2 expression was performed in 42 cases of primary mucinous carcinomas (colorectal=10, breast=14, cervix=10, stomach=8) and 22 cases of metastatic mucinous colorectal carcinoma. The predictive capacity of SATB2 and CDX2 expression for diagnosing the mucinous carcinoma of colorectal origin was determined individually and in combination using sensitivity, specificity, and positive and negative predictive value calculations. Results SATB2 demonstrated positive immunoreactivity in all cases of primary colorectal carcinoma and 81.8% of metastatic colorectal carcinomas in addition to 57.1% of breast, 40% of cervical, and 25% of gastric tumors. CDX2 was positively expressed in 60% of primary colorectal carcinomas and 72.7% of metasty tatic colorectal carcinomas, but it was negative in all noncolonic primary mucinous carcinomas. The SATB2 expression showed a sensitivity of 100% and a specificity of 56.2% in identifying colorectal origin of mucinous carcinomas, compared with 60 and 100% for CDX2 expression, respectively. The combined use of both SATB2 and CDX2 raised both the sensitivity and the negative predictive values to 100% if any of the two markers showed positivity as compared with the isolated use of CDX2. Conclusion SATB2 is a more sensitive yet less specific marker for diagnosis of mucinous carcinoma of colorectal origin as compared with CDX2. SATB2 in combination with CDX2 increases the accuracy of distinguishing mucinous carcinomas of colorectal origin from mucinous carcinomas of other origins; therefore, SATB2 is considered a useful marker in this respect.

Research paper thumbnail of Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression

Applied immunohistochemistry & molecular morphology : AIMM, Jan 30, 2017

Loss in apoptosis competence often results in augmented genomic instability contributing to carci... more Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0...

Research paper thumbnail of Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency

Folia Neuropathologica, 2017

Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the c... more Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the cerebrospinal venous outflow routes, which is postulated to cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to iron deposition which triggers inflammation and demyelination in MS. Invasive endovascular treatment of CCSVI was initiated based on the previous theory. The present study was designed to validate this hypothesis using a rat model of CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats (n = 15), and sham-operated rats (n = 15) were used as a control group. The rats were followed clinically for eight months and neurological examination detected no weakness or paralysis in the operated rats. At the end of the experiment, the rats were sacrificed and the brains were processed for histopathological examination of tissue sections stained by hematoxylin and eosin, myelin stain, silver impregnation, iron stain and immunohistochemical preparations for GFAP, CD68 and CD45. Semithin sections stained with toluidine blue were also examined. In the JVL group, increased iron deposition in the white matter was detected. An increase in the size and number of astrocytes along with increased GFAP immunoreactivity denoting reactive gliosis was also noted in the JVL group. However, no signs of demyelination, inflammation or axonopathy were detected. This study revealed that iron deposition in the JVL group as a model for CCSVI was not associated with cardinal histopathological findings of MS. It is therefore recommended that the invasive endovascular treatment of CCSVI should be reconsidered and further controlled clinical studies be carried out to provide a better understanding of the pathogeneses of MS.

Research paper thumbnail of Immunohistochemical expression of survivin in breast carcinoma: relationship with clinicopathological parameters, proliferation and molecular classification

Journal of the Egyptian National Cancer Institute

Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with... more Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinicopathological parameters, proliferation (MIB-1) and molecular classification Our retrospective study comprised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immunostained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immunonegative. Survivin expression showed significant association with increased tumor size (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), high histologic grade (p=0.04), lymph node metastases (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), advanced tumor stage (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), MIB-1 expression (p=0.02), negative estrogen receptor status (p=0.01) and negative progesterone receptor status (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes (p=0.01). Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel cancer treatment. Breast carcinoma - Immunohistochemistry - MIB-1 - Molecular classification - Survivin.

Research paper thumbnail of Diagnostic value of progesterone receptor and p53 expression in uterine smooth muscle tumors

Diagnostic Pathology, 2012

Background: The diagnosis of uterine smooth muscle tumors depends on a combination of microscopic... more Background: The diagnosis of uterine smooth muscle tumors depends on a combination of microscopic features. However, a small number of these tumors still pose difficult diagnostic challenges. Aim: To investigate progesterone receptor (PR) and p53 expression in leiomyomas (LMs), atypical leiomyomas (ALMs), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcomas (LMSs) and to evaluate the potential utility of the selected immunohistochemical markers in differentiating these tumors. Materials and methods: Immunohistochemical expression of PR and p53 was investigated in 41 uterine smooth muscle tumors comprising: 15 LMS, 4 STUMP, 6 ALM and 16 LM. Quantitative evaluation of PR and p53 expression was graded on a scale from 0 to 3+. Results: Leiomyosarcomas showed reduced PR expression. All LMs as well as ALMs and STUMP were stained intensely for PR. Conversely, LMS was strongly stained with p53, while the three non-sarcomatous groups (STUMP, ALM, LM) were either entirely negative or weakly stained for p53. Regarding both PR and p53 expression, the difference between the LMS group and the three non-sarcomatous groups was highly significant (p < 0.001). Combined high PR-low p53 expression was seen in all the 26 examined cases of the non-sarcomatous group including the STUMP cases and none of the LMS cases. Therefore, it represents a "benign" profile with 100% specificity in diagnosis of a non-sarcomatous tumor. Conclusion: Immunohistochemistry for PR and p53 is valuable as an adjunct tool to morphological assessment of problematic uterine smooth muscle tumors.

Research paper thumbnail of Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27/Kip1 labeling indices

Journal of the Egyptian National …, 2011

Background: Pituitary tumors are a common form of endocrine neoplasia. However few studies assess... more Background: Pituitary tumors are a common form of endocrine neoplasia. However few studies assessed the expression of the principal cyclin regulating checkpoint exit, cyclin D1. Cyclin D1 expression in pituitary tumors and its possible relation to MIB-1 and p27/Kip1 labeling indices (LIs) was explored. Design: We studied a total of 199 pituitaries, including normal pituitaries (n = 7), pituitary adenomas (n = 187), and pituitary carcinoma (n = 5). All tissues were tested as cores of archived tissue microarrays that were immunostained for cyclin D1, MIB-1 and p27 using a standard technique. Tissue cores were subjected to automated analysis to evaluate the staining LIs. Results: No cyclin D1 positive cells in the normal anterior pituitary gland was found. Sparse nuclear staining was noted in pituitary tumors. Higher expression of cyclin D1 was noted in pituitary carcinomas compared to adenomas (p < 0.001), in non-functioning adenomas compared to functioning ones (p < 0.001) in macroadenomas versus microadenomas (p = 0.017) and in recurrent non recurrent adenomas (p < 0.001). Cyclin D1 LI and MIB-1 LI were related among adenomas (p < 0.001) and carcinomas (p = 0.041). p27 LI was neither related to pituitary adenoma recurrence nor invasion. Conclusions: Expression of cyclin D1 in pituitary tumors is related to cell proliferation, recurrence, and metastatic potential. Nuclear cyclin D1 expression is a good marker of aggressive behavior in pituitary tumors.

Research paper thumbnail of Perspectives on the immunologic microenvironment of astrocytomas

Cancer Management and Research, 2013

Background: The microenvironment of astrocytomas includes infiltrative inflammatory cells that ar... more Background: The microenvironment of astrocytomas includes infiltrative inflammatory cells that are dynamic in nature, possibly reflecting tumor biology. We evaluated the inflammatory cell infiltrate in astrocytic tumors aiming for a better understanding of their immunobiology. Methods: Immunohistochemical expression of CD68, CD3, and CD20 was investigated in 21 glioblastomas, 21 anaplastic astrocytomas, 13 diffuse astrocytomas, and 18 pilocytic astrocytomas. The inflammatory infiltrate was classified based on microanatomic location as perivascular and intratumoral, and subsequently graded semiquantitatively. Results: Perivascularly, CD68-positive infiltrate was noted in 71.4% of glioblastomas compared with 14.3% of anaplastic astrocytomas (P = 0.0001), 7.7% of diffuse astrocytomas (P = 0.0001), and 33.3% of pilocytic astrocytomas (P = 0.017). Intratumorally, 85.7% of glioblastomas exhibited CD68-positive infiltrate compared with 42.9% of anaplastic astrocytomas (P = 0.004), 38.5% of diffuse astrocytomas (P = 0.008), and 33.3% of pilocytic astrocytomas (P = 0.001). Among diffusely infiltrating astrocytomas, intratumoral CD3-positive infiltrate was only associated with glioblastoma. A CD20-positive infiltrate was only detected in the perivascular space of a single case of diffuse astrocytoma. Conclusion: These data indicate a distinct immune profile in the glioblastoma microenvironment primarily related to the prevalence of macrophages. Thus, novel glioblastoma therapies should address this key CD68-positive population and its possible role in generating an antitumor immune response.