Shahid Pervez - Academia.edu (original) (raw)

Papers by Shahid Pervez

JPMA. The Journal of the Pakistan Medical Association, 1994

Nature Communications, 2021

Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises sys... more Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-memberBATF3andIL-2 receptor(IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases followingBATF3knockout, and BATF3 is recruited toIL2Rregulatory regions. Functionally, IL-2, IL-15 and Neo-2/15, a hyper-stable IL-2/IL-15 mimic, accelerate ALCL growth and activate STAT1, STAT5 and ERK1/2. In line, strong IL-2Rα-expression in ALCL patient...

Blood, 2020

Anaplastic Large Cell Lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactiv... more Anaplastic Large Cell Lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive Anaplastic Lymphoma Kinase (ALK) fusion protein. ALK inhibitors such as crizotinib provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by NPM1-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54-90% in clinical trials. However, a subset of patients progress within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide CRISPR activation and knockout screens in ALCL cell lines combined with RNA-seq data derived from ALK inhibitor relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of IL10RA. Elevated IL10RA expression rewires the STAT3 signaling pathway bypassing otherwise critical phosphorylation by NPM1-ALK. IL10RA expression does not correl...

PLOS ONE, 2020

Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is th... more Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is the first and second most common cancer in males and females of Pakistan respectively. Major risk factors include peculiar chewing habits like areca nut, betel quid, and tobacco. The majority of OSCC presents at an advanced stage with poor prognosis. On the face of such a high burden of this preventable cancer, there is a relative lack of recent robust data and its association with known risk factors from Pakistan. The aim of this study was to identify the socioeconomic factors and clinicopathological features that may contribute to the development of OSCC. A total of 186 patients diagnosed and treated at a tertiary care hospital, Karachi Pakistan were recruited. Clinicopathological and socioeconomic information was obtained on a structured questionnaire. Descriptive analysis was done for demographics and socioeconomic status (SES) while regression analysis was performed to evaluate the association between SES and chewing habits, tumor site, and tumor stage. The majority of patients were males and the mean age of OSCC patients was 47.62±12.18 years. Most of the patients belonged to low SES (68.3%) and 77.4% were habitual of chewing. Gender (male) and SES were significantly associated with chewing habits (p<0.05). Odds of developing buccal mucosa tumors in chewers (of any type of substance) and gutka users were 2 and 4 times higher than non-chewers respectively. Middle age, chewing habits, and occupation were significantly associated with late stage presentation of OSCC (p<0.05). In conclusion, male patients belonging to low SES in their forties who had chewing habits for years constituted the bulk of OSCC. Buccal mucosa was the most common site in chewers and the majority presented with late stage tumors.

$Research paper thumbnail of Ewing\u27s sarcoma arising from the adrenal gland in a young male: a case report$

Background: Ewing\u27s sarcoma uncommonly arises from extraosseous soft tissue or parenchymal org... more Background: Ewing\u27s sarcoma uncommonly arises from extraosseous soft tissue or parenchymal organs. Primary adrenal Ewing\u27s Sarcoma, although very rare, is extremely aggressive and commonly fatal. CASE PRESENTATION: A 17 year old Pakistani male was referred to the outpatient oncology clinic at our center with a three month history of concomitant pain, swelling and dragging sensation in the right hypochondrium. Abdominal examination revealed a large, firm mass in the right hypochondrium extending into the right lumbar region and epigastrium. His genital exam was unremarkable and there were no stigmata of hepatic or adrenal disease.Computed tomography scans revealed a large peripherally enhancing mass in the hepatorenal area, biopsy of which showed a neoplastic lesion composed of small round blue cells which exhibited abundance of glycogen and stained diffusely positive for CD99 (MIC2 antigen). Fluorescence in situ hybridization demonstrated gene rearrangement at chromosome 22q12...

Canadian journal of surgery. Journal canadien de chirurgie, 2002

P aragangliomas are uncommon tumours that have been described in virtually every site in which no... more P aragangliomas are uncommon tumours that have been described in virtually every site in which normal paraganglia are known to occur. Paragangliomas of the carotid body represent the most common group of extra-adrenal paragangliomas. The other less common sites include jugulotympanic, vagal, mediastinal and retroperitoneal. Paragangliomas have been described in the gastrointestinal tract especially in the duodenum. Paraganglioma as a mesenteric mass is extremely rare and only occasional reports have been published. 1-3 Our case of mesenteric paraganglioma in a 76-year-old woman is probably only the fourth published case.

J Pak Med Assoc, Dec 1, 1993

This Is a retrospective quality assurance study of all frozen sections done at The Aga Khan Unive... more This Is a retrospective quality assurance study of all frozen sections done at The Aga Khan University Hospital during a six year period (1986 to 1991). There were 1,031 frozen sections out of a cumulative total of 42,985 surgical specimens (2.39%). Nine hundred and seventy-six (94.66%) were concordant. In 92(8.9%) fresh specimens were brought from other hospitals of Karachi, in 37 cases (3.58%) the diagnosis was deferred till the evaluation of permanent paraffin sections and 18 (1,74%) were discordant with 7 (0.67%) false positive and 11(1,06%) false negative. Among the discordant cases, 9 were attributed to misinterpretation, 7 due to sampling errors and 2 due to technical reasons. Some of these errors might have been avoided, but appear to be an Irreducible minimum (J PMA 43:253, 1993).

Predictive pathology is a unique addition in an otherwise predominant diagnostic focus of this at... more Predictive pathology is a unique addition in an otherwise predominant diagnostic focus of this atlas. In the last few decades, a large number of ‘predictive markers’ for various cancers in particular ‘breast’, ‘stomach’ and ‘lung’ among others were validated and now an integral part of standard patient care. Pathologists particularly histopathologists play a pivotal role in this exercise. Beginning with ‘oestrogen and progesterone receptor’ assessment in breast cancer, the list of such predictive markers has seen an exponential growth like HER2 testing in breast and gastric cancer, EGFR mutational analyses and ALK testing in non-small cell lung carcinoma (adenocarcinoma). Proliferative markers like Ki-67 labelling are also commonly used in a wide variety of tumours. In lymphomas, particularly ‘diffuse large B-cell lymphoma’, distinction between ‘germinal centre and activated B-cell’ phenotype is often requested, while markers like c-myc, bcl2 and bcl6 are required to distinguish double- or triple-hit lymphomas among high-grade B-cell lymphomas. Prime reason for this explosion is the specific personalized or precision treatment availability based on individualized tumour analysis, targeting or blocking the pathways fuelling the tumour growth. More recently with the approval of ‘immune checkpoint inhibitors’, testing for PD-L1 by IHC to predict usefulness of therapy is required. An important aspect of all these predictive markers is the validation of testing as well as correct interpretation or scoring as per international like ASCO/CAP guidelines. In this chapter quick reporting guidelines are provided to help pathologists to minimize any such errors by liberal use of IHC and FISH images

Haematolymphoid pathology is one of the most diverse and challenging area of diagnostic pathology... more Haematolymphoid pathology is one of the most diverse and challenging area of diagnostic pathology by virtue of the immense diversity and complexity of immune system itself. Precise categorization of haematolymphoid neoplasms also invariably require immunophenotyping by ‘immunohistochemistry (IHC)’ or/and ‘flow cytometry’ in addition to molecular genetic testing by FISH or PCR. Common biopsy sites include ‘lymph node’ from all regions, extra-nodal sites in particular from GIT, though no site is exempt as well as ‘bone trephine’. In this chapter both non-neoplastic and neoplastic lesions are covered, though major focus is on salient microscopic features both at architectural and cellular level along with judicious use of IHC and other ancillary testing of haematolymphoid neoplasms to differentiate these from close mimicries on one hand and from atypical reactive patterns on the other.

$Research paper thumbnail of Childhood non-Hodgkin\u27s Lymphoma: An immunophenotypic analysis$

Objective: To observe the frequency of histological subtypes of childhood non-Hodgkin`s lymphoma ... more Objective: To observe the frequency of histological subtypes of childhood non-Hodgkin`s lymphoma and its immunohistochemical profile. Setting: All cases of non-Hodgkin’s lymphoma diagnosed in children (\u3c15 years) in the section of histopithology at the Aga Khan University Hospital Karachi during the period of three years. Methods: These consecutive cases were evaluated on H&E stained sections and then immunohistochemistry analysis of these tumors was performed by employing Peroxidase Anti-Peroxidase (PAP) technique. Results: The present series included 61 cases of non-Hodgkin’s lymphoma. NHL was more common in males as compared to females with male to female ratio of 5.8:1. High grade NHL comprised 87% of childhood lymphoma. The mode of presentation in majority of NHL (57%) was extranodal. Burkitt’s lymphonia (33%) was the most prevalent histological subtypes, followed by lymphoblastic (28%), diffuse large cell (15%), diffuse mix small and large cell (13%), small non cleaved Non-...

JPMA. The Journal of the Pakistan Medical Association, 1998

Histologic diagnosis ultimately determines the prognosis and treatment of lesions causing spinal ... more Histologic diagnosis ultimately determines the prognosis and treatment of lesions causing spinal cord compression. Modern imaging techniques have revolutionized the procedure of localizing lesions presenting with signs and symptoms of spinal cord compression. As a result, these lesions are more accessible for fine needle aspiration and biopsy. A quick diagnosis is possible if cytologic preparation is made. Similarly, intraoperative frozen section facility not only provides rapid diagnosis, but also offers opportunity of appropriate management decision there and then. Histology in many cases needs help of special stains and immunocytochemistry. This study looks at the histologic spectrum of these lesions, gender distribution and age range in Pakistani population.

JPMA. The Journal of the Pakistan Medical Association, 1996

JPMA. The Journal of the Pakistan Medical Association, 1993

JPMA. The Journal of the Pakistan Medical Association, 2002

Axillary lymph node involvement in primary breast cancer is one of its most important prognostic ... more Axillary lymph node involvement in primary breast cancer is one of its most important prognostic features. Thus any factors that may predict axillary lymph node involvement in this setting could be potentially helpful in treatment planning and other interventions. The objective of this study was to evaluate clinical, pathological and immuno-histochemical markers in univariate and multivariate analysis, which may be helpful predictors of axillary lymph node involvement in breast cancer. A retrospective analysis of 555 cases. Of these 58% had axillary nodal positivity and 42% were negative. Factors of no significance included patient's age, height, weight, age of first pregnancy, parity, marital status, menopausal status, family history of breast cancer, side of tumor. In univariate analysis the age of menarche, duration of symptoms, tumor size, site in outer quadrant, S phase and skin and nipple involvement all predicted axillary nodal involvement. The length of breast-feeding, i...

JPMA. The Journal of the Pakistan Medical Association, 1999

Journal of the College of Physicians and Surgeons, 2011

Association of Helicobacter pylori (H. Pylori) infection with gastric 'Mucosa Associated Lymp... more Association of Helicobacter pylori (H. Pylori) infection with gastric 'Mucosa Associated Lymphoid Tissue' (MALT) lymphomas (MALTomas) is well established. In this study the frequency and characteristics of gastric MALToma over a period of 18 years was evaluated. During this period 24 patients with gastric MALToma were diagnosed; out of them, 13 (54.2%) had active H. Pylori infection. The mean and median age was 49.7 and 53.5 years. The male: female ratio was 17:7. The common presenting complaints were epigastric pain (n=10) and dyspepsia (n=9). Endoscopic findings revealed mild gastric hyperemia (n=16), superficial erosions (n=4) and superficial ulcers (n=4). It was concluded that the prevalence of gastric MALToma was very low in contrast to a high H. pylori gastritis in the Pakistani population.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2011

This study describes the frequency, demographics, clinical presentation, endoscopic findings, his... more This study describes the frequency, demographics, clinical presentation, endoscopic findings, histopathological features, treatment and outcome of 'Immunoproliferative small intestinal disease' (IPSID). Archives contained a total of 27 cases of IPSID diagnosed and treated over an 18-year period. A M: F ratio of 2.4:1 was seen with a mean and median ages of 28.7 and 25 years. Most patients (68.8%) presented with abdominal pain and diarrhoea. In the majority (62.5%), duodenum was the primary site of involvement. Endoscopy showed polypoidal, raised or flat lesions. Biopsy findings included blunting or flattening of villi with dense plasma cell infiltrate and lymphoepithelial lesions. Twenty-four cases were categorized as stage A and B (benign and intermediate) and three were categorized as stage C (malignant, diffuse large B-cell lymphoma with plasmacytoid features). Stage A and B patients responded well to antibiotic treatment (tetracycline) with regression of the lesions whil...

JOURNAL OF PAKISTAN MEDICAL ASSOCIATION, 1999

To determine the prevalence of Hodgkin's disease (HD) and its various subtypes in children an... more To determine the prevalence of Hodgkin's disease (HD) and its various subtypes in children and adults and assess the use of immunohistochemical (IHC) studies in confirming HD cases and excluding its close mimicries/look-alikes. All 265 Hodgkin's disease cases diagnosed at The Aga Khan University Hospital, Karachi over the last 6 years (July 1991-July 1997) were included. Of these 219 were diagnosed on routine H&E examination while in the remaining 46 cases, diagnosis was made after a thorough IHC workup. (This group initially included 161 cases labelled as lymphoproliferative disorder with HD as one of the differentials). Out of a total of 265 HD cases (206) 78% were males and (59) 22% were females in a ratio of 3.5:1.26% (69) cases were < 15 years while 74% (196) were > 15 years old. In both age groups, the commonest subtype proved to be Mixed Cellularity (MC) (60% of < 15 years old and 40% of > 15 years old) followed by Nodular Sclerosing (NS) (20% of < 15 y...

JOURNAL OF PAKISTAN MEDICAL ASSOCIATION, 2004

To review the cases sent to the section of histopathology, Aga Khan Universty (AKU) for second op... more To review the cases sent to the section of histopathology, Aga Khan Universty (AKU) for second opinion and see whether there are significant differences in the original outside diagnosis and the subsequent diagnosis submitted by us. A retrospective study of all consecutive cases for second opinion in the form of paraffin blocks from 1st Novemver 2001 to 31st July 2002. The primary submitted diagnosis in each case was compared with the subsequent AKU diagnosis. The study included a total of 381 cases. However, in 45 cases (11.81%), initial histopathological diagnosis was not provided. Out of the remaining 336 cases, there were differences between the original diagnosis and the subsequent AKU diagnosis in 120 cases (35.71%). Out of these 120 cases, immunohistochemistry was performed in 65 cases (54.16%) only. In a developing country like Pakistan, where few laboratories are equipped to function as modern histopathology units, second opinion on difficult cases is very important. Worldw...

SpringerPlus, 2014

PurposeTo investigate the promoter methylation status at selected loci which encode for key prote... more PurposeTo investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.MethodsTotal genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle invasive high grade bladder cancer were also subjected to similar analyses.ResultsPromoter hypermethylation was frequently observed in RASSF1A, APC and MGMT gene promoters (p-value < 0.001). The methylation was more prominent in the muscle invasive high grade bladder cancer when compared to non-muscle invasive low grad...