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Papers by Antonio Llombart-cussac

Diagnostic Molecular Pathology, 2002

International Journal of Molecular Sciences

Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the... more Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical options. Three cases of IS were collected from two institutions. Clinical data were retrieved and histological study was performed. A wide immunohistochemical panel was analyzed. FISH of MDM2 gene was performed, and a molecular study with NGS was implemented in all cases. The mean age of our cases was 54 years. Histologically, the tumors presented a diffuse growth pattern with heterogeneous atypical epithelioid or spindle cells and extensive thrombosed areas. All cases presented intense immunoexpression for MDM2, CDK4, CD117, c-myc, PDGFRA, and p16. PDGFRA, HTERT, and pan-TRK gained expression, while p16 lost intensity, being weaker in both the local recurrences and xenografts. The three cas...

American Journal of Clinical Pathology, 2006

Histology and histopathology, 2020

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. ... more Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.

Virchows Archiv, 2013

Galectin-1 (GAL-1) is frequently expressed in osteosarcomas. Although a valuable diagnostic marke... more Galectin-1 (GAL-1) is frequently expressed in osteosarcomas. Although a valuable diagnostic marker to differentiate between chondroblastic osteosarcomas and conventional chondrosarcomas, it has not been tested in the Ewing sarcoma family of tumors (ESFTs). We studied by immunohistochemistry GAL-1 expression in 43 osteosarcomas, 23 chondrosarcomas, and 217 genetically confirmed ESFTs using a tissue microarray. GAL-1 was expressed in 78 % of osteosarcomas, 33 % of chondrosarcomas, and 8 % of ESFTs. Osteoblastic and small cell osteosarcoma subtypes expressed GAL-1 in a high percentage of cells when compared with the other histological subtypes, whereas two chondroblastic osteosarcomas were negative. GAL-1 was mainly expressed in high-grade chondrosarcomas (grade III). ESFTs were rarely positive (8 %), and this was not related to the histological subtype nor to the clinical outcome. Although GAL-1 expression distinguishes chondroblastic osteosarcomas from conventional chondrosarcomas and is usually negative in conventional chondrosarcomas, the final diagnosis needs to incorporate histopathology since some chondroblastic osteosarcomas fail to express GAL-1, while high-grade chondrosarcomas are GAL-1 positive. Since GAL-1 is frequently expressed in osteogenic tumors, including small cell osteosarcoma, but rarely positive in ESFTs, its expression seems a valuable tool for distinguishing between these lesions. GAL-1 immunoexpression is not indicative of prognosis in ESFT.

Virchows Archiv, 2006

This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous... more This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous (MFSS), and poorly differentiated (PDSS)] and tissue microarray (TMA) evaluation of the immunophenotypic and histological progression of SSs in nude mice using three TMAs comprising 11 primary SSs (8 MFSSs, 2 BSSs, and 1 PDSS) and their xenografts. BSS and MFSS progressively transformed to a similar undifferentiated phenotype with loss of glandular component in the xenografts. Epidermal growth factor receptor and SALL2 were expressed in primary tumors and xenografts. Enhanced bcl-2 and bax expression were noted in xenografts. Ki-67 overexpression in xenografts correlated with high mitotic index. Epithelial membrane antigen (EMA) and cytokeratin AE1/AE3 were detected in all original and xenografted SSs. Hierarchical clustering differentiated original MFSS and BSS, but their xenografts clustered together due to similar immunoexpression profile. Our study demonstrates definite phenotypic variability of BSS and MFSS in the xenografts. Differences in immunoexpression for various markers existed between primary tumor and xenografts but not between subtypes. Hierarchical clustering grouped TMA immunostaining data and confirmed immunophenotypic variability; however, it failed to reveal any immunophenotypic differences between SYT-SSX1 and SYT-SSX2 type tumors. Nonetheless, reversetranscriptase-polymerase chain reaction detected SYT-SSX transcripts in all primary SSs and their xenografts, thereby demonstrating their genetic stability. Keywords Synovial sarcoma. Nude mice xenografts. Tissue microarrays. Novel markers. Hierarchical cluster analysis Abbreviations SS synovial sarcoma MFSS monophasic fibrous synovial sarcoma BSS biphasic synovial sarcoma PDSS poorly differentiated synovial sarcoma TMA tissue microarray RT-PCR reverse-transcriptase-polymerase chain reaction EGFR epidermal growth factor receptor SALL2 SAL (drosophila)-like 2 IGFBP2 insulin-like growth factor binding protein 2

Virchows Archiv, 2012

Epithelial marker and adhesion molecule expression has been reported in Ewing&amp... more Epithelial marker and adhesion molecule expression has been reported in Ewing's sarcoma family of tumors (ESFTs), although the prognostic significance has not been assessed systematically. We performed immunohistochemical analysis of epithelial cell adhesion molecule and epithelial mesenchymal transition markers on 415 genetically confirmed ESFTs. Survival analyses were performed in 217 patients. The atypical histological subtype expressed a high proportion of the epithelial markers compared with conventional and PNET variants. We observed that expression of desmoplakin (p < 0.001) and PI3K (p = 0.003) was higher in disseminated than in localized disease. Multivariate analysis showed that desmoplakin and pGSK3β constitute independent good prognostic factors for progression free survival (PFS), while ZO-1 and Snail represent independent good prognostic factors for overall survival (OS). In contrast, CK8/18 represents an independent poor prognostic factor for OS and the radiotherapy treatment group demonstrated an independent poor prognostic factor for PFS and OS. Although the expression of pan-cytokeratin has been previously highlighted in a significant proportion of ESFT, its expression did not reveal prognostic significance in the present series. Considering the results of prognostic analysis herein reported, we strongly recommend a prospective validation of at least the immunomarkers with prognostic significance (desmoplakin, ZO-1, CK8/18, pGSK3β, and Snail) in prospective series that include localized and disseminated tumors.

International Journal of …

Virchows Archiv, 2004

Previous studies have shown that during the period subsequent to the Chernobyl accident, increase... more Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of re-nal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the ...

Pathology & Oncology …, 2009

Apoptosis-related proteins and proliferation activity and their relationship with Epstein-Barr Vi... more Apoptosis-related proteins and proliferation activity and their relationship with Epstein-Barr Virus (EBV) are contemporary issues in pediatric non-Hodgkin's lymphoma (pNHL). In this study prognostic or pathogenetic role of EBV latent infection, proliferating activity, and apoptosisregulating proteins in pNHL were explored. EBV-EBER, lmp-1, ki-67, bcl-2, survivin, bax, fas, c-myc, p53 and apoptotic index by TUNEL method were explored in 70 pNHL cases and evaluated statistically. Of the 70 cases evaluated, 24 were female and 46 were male. Seven cases were stage I/II and 63 cases were stage III/IV. The mean age was 7.16±3.72(1-15). EBV was positive in (25.7%) cases. Overall survival was 82%, while event free survival was 75%. Bax was expressed in 40% of the cases, while the expression of bcl-2,was 50%, survivin 42.9%, p53 8.6%, fas 18.6% and c-myc in 45.7%. Mean apoptotic index was 131.29±96.69 per 5,000 cells. Mean proliferation index was 55.97% (12-92%). Fas positivity was high in EBV positive cases (p=0.0001). EBV positivity was not related with prognosis. Apoptotic index was found to be an independent prognostic factor (p=0.017). Our results suggest that apoptosis-regulating proteins have a role in the pathogenesis of pNHL. EBV was correlated with apoptotic index and fas, bcl-2. No correlation was observed with proliferation index and studied factors. High apoptotic index was related with good prognosis.

Cancers

Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (... more Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (NSCLC). To date, however, only a few agents have shown promising results. Recent advances in cancer immunotherapy, most notably immune checkpoint inhibitors (ICI), have transformed the treatment scenario for these patients. Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. New biomarkers capable of reliably predicting response to ICIs are urgently needed to improve patient selection. Currently available biomarkers—including programmed death protein 1 (PD-1) and its ligand (PD-L1), and tumor mutational burden (TMB)—have major limitations. At present, no well-validated, reliable biomarkers are available. Ideally, these biomarkers would be obtained through less invasive methods such as plasma determination or liquid biopsy. In the present review, we describe recent advances in the develop...

International Journal of Molecular Sciences

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopat... more Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On...

Cancers

Background: Studies of patients with cancer affected by coronavirus disease 2019 (COVID-19) are n... more Background: Studies of patients with cancer affected by coronavirus disease 2019 (COVID-19) are needed to assess the impact of the disease in this sensitive population, and the influence of different cancer treatments on the COVID-19 infection and seroconversion. Material and Methods: We performed a retrospective analysis of all patients hospitalized with RT-PCR positive for COVID-19 in our region to assess the prevalence of cancer patients and describe their characteristics and evolution (Cohort 1). Concurrently, a transversal study was carried out in patients on active systemic cancer treatment for symptomatology and seroprevalence (IgG/IgM by ELISA-method) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (Cohort 2). Results: A total of 215 patients (Cohort 1) were admitted to hospital with a confirmed COVID-19 infection between February 28 and April 30, 2020, and 17 died (7.9%). A medical record of cancer was noted in 43 cases (20%), 6 of them required Intensi...

JNCI: Journal of the National Cancer Institute

Background CDK4/6-inhibitors (CDK4/6i)+endocrine therapy (ET) prolonged progression-free survival... more Background CDK4/6-inhibitors (CDK4/6i)+endocrine therapy (ET) prolonged progression-free survival as first/second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) prognosis. Given the recent publication of overall survival (OS) data for the three CDK4/6i, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. Methods We conducted a systematic literature search to select all available phase II/III randomized clinical trials of CDK4/6i+ET reporting OS data in first/second-line therapy of HR+/HER2-negative pre/postmenopausal MBC. A random effect model was applied for the analyses. Heterogeneity was assessed with I2 statistic. Subgroup analysis were performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP). Results Six studies were included in our analyses (3,421 patients). A c...

The American Journal of dermatopathology, Jan 27, 2018

Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon ... more Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon in angiosarcomas (AS) and creates a challenging differential diagnosis with other superficial or soft tissue tumors. Herein, we report a new case of superficial AS presenting as a tumor lesion on the little finger of the right hand of a 52-year-old man. The tumor displayed CD56, chromogranin-A, and synaptophysin immunoreactivity. Tumor cells were positive for vascular markers (CD31, FLI1, ERG, D2-40, VE-cadherin, VEGR1,2, and 3), CD99, and EMA, but were negative for S100, CK (AE1/AE3), CK20, polyomavirus, and myogenic (desmin and myogenin) and melanocyte markers (melan-A and HMB45). Ki67 immunostains indicated high proliferative activity (>50%). The whole-body computed tomography did not reveal distant disease. The initial assessment considered several tumor subtypes as possible histological diagnoses, including Ewing sarcoma, Ewing-like sarcoma, Merkel cell carcinoma, and undifferent...

Virchows Archiv : an international journal of pathology, 2018

Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltratin... more Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of PD-L1 and PD-1 and their prognostic significance in clinically localized neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was done considering only clinically localized tumors (n = 217). PD-L1 expression was present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated proliferation index (Ki-67) were associated with higher PD-L1 expression (p = 0.049). Regarding prognosis, no significant as...

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, Jun 1, 2018

Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angio... more Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm-4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). Results We observed histological, ultrastructural, and immuno...

Annals of diagnostic pathology, Jan 29, 2017

Despite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findi... more Despite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findings, a group of round/ovoid cell tumors histologically similar to Ewing sarcomas (ES) but lacking EWSR1-rearrangements may remain unclassifiable. We retrospectively analyzed 41 Ewing-like tumors (formalin-fixed, paraffin-embedded) previously determined as negative or non-informative for EWSR1-rearrangements by FISH and/or RT-PCR. A new histopathology revision and additional IHC and molecular analyses were carried out in order to investigate whether additional IHC and/or molecular testing in combination with the morphological findings may help in reaching a definitive diagnosis. Almost all the tumors (n=40) involved soft tissue and/or bone and half the patients died of disease. In the archival cases all diagnoses were Ewing sarcoma (ES), Ewing-like sarcoma (ELS), myoepithelial tumor and undifferentiated sarcoma (US). In the new review all the tumors were re-classified as, ES (n=16), Ewing...

International Journal of Surgical Pathology

Eight conventional and six atypical oncocytomas in a series of 147 renal neoplasms were studied. ... more Eight conventional and six atypical oncocytomas in a series of 147 renal neoplasms were studied. Histopathologic findings revealed exclusively oncocytic cells, but cellular polymorphism was higher in the atypical tumors. Atypical oncocytomas presented focal necrosis, transcapsular invasion, or both. Electron microscopy showed similar findings in all cases. Immunohistochemistry of atypical oncocytomas had higher expression against proliferating cell nuclear antigen and more discontinuous immunostaining against laminin than typical ones. Flow cytometry revealed one or two aneuploid peaks in five typical and two atypical cases, although the latter had a higher proliferative fraction than typical oncocytomas. Cytogenetics of one typical oncocytoma showed a normal diploid karyotype; one atypical case resulted in a diploid karyotype but with endoreduplications in 13% of metaphases, and a second atypical oncocytoma became hypodiploid without structural anomalies. Based on the present resul...

Pathology - Research and Practice

Ewing sarcoma is an aggressive neoplasm of pediatric and adolescent patients. Immunohistochemistr... more Ewing sarcoma is an aggressive neoplasm of pediatric and adolescent patients. Immunohistochemistry (IHC) can be used to support the morphologic diagnosis of Ewing sarcoma family of tumors (ESFT) in a convincing clinical/radiological context. Although neither NKX2.2 nor CD99 alone are entirely specific, when combined, the diagnostic specificity is high. The aim of the present study was to investigate the IHC expression of NKX2.2, ETV4 and BCOR in a large series of genetically confirmed ESFT. The results for CD99 and CAV-1 immunoreactivity, and the histological and fusion gene subtypes were retrieved from our previous study. NKX2.2 demonstrated moderate or strong nuclear positivity in 91.2% of the tumors. The staining intensity was heterogeneous. Many of the ESFT with negative NKX2.2 immunoreactivity were in bone. Strong/moderate ETV4 nuclear expression was detected in two small round cell tumors, both were negative for NKX2.2. No relationships could be found between expression of NKX2.2 and the histological subgroups or ESFT gene fusion subtypes. BCOR was negative in all ESFT. In conclusion, NKX2.2, ETV4 and BCOR IHC may be helpful in daily practice for distinguishing ESFT from CIC or BCOR-associated sarcomas, especially in hospitals without access to molecular assays. In addition, the combination of strong CD99 membranous positivity and nuclear NKX2.2 positivity seems to be very reliable for ESFT diagnosis in an appropriate clinicoradiological setting. So far no antibody is entirely specific for ESFT diagnosis, and the IHC or molecular results in round cell tumors of bone may be strongly influenced by decalcification processes.

Diagnostic Molecular Pathology, 2002

International Journal of Molecular Sciences

Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the... more Intimal sarcomas (IS) are rare malignant mesenchymal tumors arising in large blood vessels of the systemic and pulmonary circulation and also in the heart. They are morphologically similar to other spindle cell, poorly differentiated sarcomas. The prognosis is poor and depends mainly on surgical options. Three cases of IS were collected from two institutions. Clinical data were retrieved and histological study was performed. A wide immunohistochemical panel was analyzed. FISH of MDM2 gene was performed, and a molecular study with NGS was implemented in all cases. The mean age of our cases was 54 years. Histologically, the tumors presented a diffuse growth pattern with heterogeneous atypical epithelioid or spindle cells and extensive thrombosed areas. All cases presented intense immunoexpression for MDM2, CDK4, CD117, c-myc, PDGFRA, and p16. PDGFRA, HTERT, and pan-TRK gained expression, while p16 lost intensity, being weaker in both the local recurrences and xenografts. The three cas...

American Journal of Clinical Pathology, 2006

Histology and histopathology, 2020

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. ... more Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.

Virchows Archiv, 2013

Galectin-1 (GAL-1) is frequently expressed in osteosarcomas. Although a valuable diagnostic marke... more Galectin-1 (GAL-1) is frequently expressed in osteosarcomas. Although a valuable diagnostic marker to differentiate between chondroblastic osteosarcomas and conventional chondrosarcomas, it has not been tested in the Ewing sarcoma family of tumors (ESFTs). We studied by immunohistochemistry GAL-1 expression in 43 osteosarcomas, 23 chondrosarcomas, and 217 genetically confirmed ESFTs using a tissue microarray. GAL-1 was expressed in 78 % of osteosarcomas, 33 % of chondrosarcomas, and 8 % of ESFTs. Osteoblastic and small cell osteosarcoma subtypes expressed GAL-1 in a high percentage of cells when compared with the other histological subtypes, whereas two chondroblastic osteosarcomas were negative. GAL-1 was mainly expressed in high-grade chondrosarcomas (grade III). ESFTs were rarely positive (8 %), and this was not related to the histological subtype nor to the clinical outcome. Although GAL-1 expression distinguishes chondroblastic osteosarcomas from conventional chondrosarcomas and is usually negative in conventional chondrosarcomas, the final diagnosis needs to incorporate histopathology since some chondroblastic osteosarcomas fail to express GAL-1, while high-grade chondrosarcomas are GAL-1 positive. Since GAL-1 is frequently expressed in osteogenic tumors, including small cell osteosarcoma, but rarely positive in ESFTs, its expression seems a valuable tool for distinguishing between these lesions. GAL-1 immunoexpression is not indicative of prognosis in ESFT.

Virchows Archiv, 2006

This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous... more This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous (MFSS), and poorly differentiated (PDSS)] and tissue microarray (TMA) evaluation of the immunophenotypic and histological progression of SSs in nude mice using three TMAs comprising 11 primary SSs (8 MFSSs, 2 BSSs, and 1 PDSS) and their xenografts. BSS and MFSS progressively transformed to a similar undifferentiated phenotype with loss of glandular component in the xenografts. Epidermal growth factor receptor and SALL2 were expressed in primary tumors and xenografts. Enhanced bcl-2 and bax expression were noted in xenografts. Ki-67 overexpression in xenografts correlated with high mitotic index. Epithelial membrane antigen (EMA) and cytokeratin AE1/AE3 were detected in all original and xenografted SSs. Hierarchical clustering differentiated original MFSS and BSS, but their xenografts clustered together due to similar immunoexpression profile. Our study demonstrates definite phenotypic variability of BSS and MFSS in the xenografts. Differences in immunoexpression for various markers existed between primary tumor and xenografts but not between subtypes. Hierarchical clustering grouped TMA immunostaining data and confirmed immunophenotypic variability; however, it failed to reveal any immunophenotypic differences between SYT-SSX1 and SYT-SSX2 type tumors. Nonetheless, reversetranscriptase-polymerase chain reaction detected SYT-SSX transcripts in all primary SSs and their xenografts, thereby demonstrating their genetic stability. Keywords Synovial sarcoma. Nude mice xenografts. Tissue microarrays. Novel markers. Hierarchical cluster analysis Abbreviations SS synovial sarcoma MFSS monophasic fibrous synovial sarcoma BSS biphasic synovial sarcoma PDSS poorly differentiated synovial sarcoma TMA tissue microarray RT-PCR reverse-transcriptase-polymerase chain reaction EGFR epidermal growth factor receptor SALL2 SAL (drosophila)-like 2 IGFBP2 insulin-like growth factor binding protein 2

Virchows Archiv, 2012

Epithelial marker and adhesion molecule expression has been reported in Ewing&amp;amp;amp;amp... more Epithelial marker and adhesion molecule expression has been reported in Ewing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s sarcoma family of tumors (ESFTs), although the prognostic significance has not been assessed systematically. We performed immunohistochemical analysis of epithelial cell adhesion molecule and epithelial mesenchymal transition markers on 415 genetically confirmed ESFTs. Survival analyses were performed in 217 patients. The atypical histological subtype expressed a high proportion of the epithelial markers compared with conventional and PNET variants. We observed that expression of desmoplakin (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and PI3K (p = 0.003) was higher in disseminated than in localized disease. Multivariate analysis showed that desmoplakin and pGSK3β constitute independent good prognostic factors for progression free survival (PFS), while ZO-1 and Snail represent independent good prognostic factors for overall survival (OS). In contrast, CK8/18 represents an independent poor prognostic factor for OS and the radiotherapy treatment group demonstrated an independent poor prognostic factor for PFS and OS. Although the expression of pan-cytokeratin has been previously highlighted in a significant proportion of ESFT, its expression did not reveal prognostic significance in the present series. Considering the results of prognostic analysis herein reported, we strongly recommend a prospective validation of at least the immunomarkers with prognostic significance (desmoplakin, ZO-1, CK8/18, pGSK3β, and Snail) in prospective series that include localized and disseminated tumors.

International Journal of …

Virchows Archiv, 2004

Previous studies have shown that during the period subsequent to the Chernobyl accident, increase... more Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of re-nal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the ...

Pathology & Oncology …, 2009

Apoptosis-related proteins and proliferation activity and their relationship with Epstein-Barr Vi... more Apoptosis-related proteins and proliferation activity and their relationship with Epstein-Barr Virus (EBV) are contemporary issues in pediatric non-Hodgkin's lymphoma (pNHL). In this study prognostic or pathogenetic role of EBV latent infection, proliferating activity, and apoptosisregulating proteins in pNHL were explored. EBV-EBER, lmp-1, ki-67, bcl-2, survivin, bax, fas, c-myc, p53 and apoptotic index by TUNEL method were explored in 70 pNHL cases and evaluated statistically. Of the 70 cases evaluated, 24 were female and 46 were male. Seven cases were stage I/II and 63 cases were stage III/IV. The mean age was 7.16±3.72(1-15). EBV was positive in (25.7%) cases. Overall survival was 82%, while event free survival was 75%. Bax was expressed in 40% of the cases, while the expression of bcl-2,was 50%, survivin 42.9%, p53 8.6%, fas 18.6% and c-myc in 45.7%. Mean apoptotic index was 131.29±96.69 per 5,000 cells. Mean proliferation index was 55.97% (12-92%). Fas positivity was high in EBV positive cases (p=0.0001). EBV positivity was not related with prognosis. Apoptotic index was found to be an independent prognostic factor (p=0.017). Our results suggest that apoptosis-regulating proteins have a role in the pathogenesis of pNHL. EBV was correlated with apoptotic index and fas, bcl-2. No correlation was observed with proliferation index and studied factors. High apoptotic index was related with good prognosis.

Cancers

Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (... more Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (NSCLC). To date, however, only a few agents have shown promising results. Recent advances in cancer immunotherapy, most notably immune checkpoint inhibitors (ICI), have transformed the treatment scenario for these patients. Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. New biomarkers capable of reliably predicting response to ICIs are urgently needed to improve patient selection. Currently available biomarkers—including programmed death protein 1 (PD-1) and its ligand (PD-L1), and tumor mutational burden (TMB)—have major limitations. At present, no well-validated, reliable biomarkers are available. Ideally, these biomarkers would be obtained through less invasive methods such as plasma determination or liquid biopsy. In the present review, we describe recent advances in the develop...

International Journal of Molecular Sciences

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopat... more Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On...

Cancers

Background: Studies of patients with cancer affected by coronavirus disease 2019 (COVID-19) are n... more Background: Studies of patients with cancer affected by coronavirus disease 2019 (COVID-19) are needed to assess the impact of the disease in this sensitive population, and the influence of different cancer treatments on the COVID-19 infection and seroconversion. Material and Methods: We performed a retrospective analysis of all patients hospitalized with RT-PCR positive for COVID-19 in our region to assess the prevalence of cancer patients and describe their characteristics and evolution (Cohort 1). Concurrently, a transversal study was carried out in patients on active systemic cancer treatment for symptomatology and seroprevalence (IgG/IgM by ELISA-method) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (Cohort 2). Results: A total of 215 patients (Cohort 1) were admitted to hospital with a confirmed COVID-19 infection between February 28 and April 30, 2020, and 17 died (7.9%). A medical record of cancer was noted in 43 cases (20%), 6 of them required Intensi...

JNCI: Journal of the National Cancer Institute

Background CDK4/6-inhibitors (CDK4/6i)+endocrine therapy (ET) prolonged progression-free survival... more Background CDK4/6-inhibitors (CDK4/6i)+endocrine therapy (ET) prolonged progression-free survival as first/second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) prognosis. Given the recent publication of overall survival (OS) data for the three CDK4/6i, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. Methods We conducted a systematic literature search to select all available phase II/III randomized clinical trials of CDK4/6i+ET reporting OS data in first/second-line therapy of HR+/HER2-negative pre/postmenopausal MBC. A random effect model was applied for the analyses. Heterogeneity was assessed with I2 statistic. Subgroup analysis were performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP). Results Six studies were included in our analyses (3,421 patients). A c...

The American Journal of dermatopathology, Jan 27, 2018

Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon ... more Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon in angiosarcomas (AS) and creates a challenging differential diagnosis with other superficial or soft tissue tumors. Herein, we report a new case of superficial AS presenting as a tumor lesion on the little finger of the right hand of a 52-year-old man. The tumor displayed CD56, chromogranin-A, and synaptophysin immunoreactivity. Tumor cells were positive for vascular markers (CD31, FLI1, ERG, D2-40, VE-cadherin, VEGR1,2, and 3), CD99, and EMA, but were negative for S100, CK (AE1/AE3), CK20, polyomavirus, and myogenic (desmin and myogenin) and melanocyte markers (melan-A and HMB45). Ki67 immunostains indicated high proliferative activity (>50%). The whole-body computed tomography did not reveal distant disease. The initial assessment considered several tumor subtypes as possible histological diagnoses, including Ewing sarcoma, Ewing-like sarcoma, Merkel cell carcinoma, and undifferent...

Virchows Archiv : an international journal of pathology, 2018

Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltratin... more Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of PD-L1 and PD-1 and their prognostic significance in clinically localized neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was done considering only clinically localized tumors (n = 217). PD-L1 expression was present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated proliferation index (Ki-67) were associated with higher PD-L1 expression (p = 0.049). Regarding prognosis, no significant as...

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, Jun 1, 2018

Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angio... more Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm-4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). Results We observed histological, ultrastructural, and immuno...

Annals of diagnostic pathology, Jan 29, 2017

Despite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findi... more Despite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findings, a group of round/ovoid cell tumors histologically similar to Ewing sarcomas (ES) but lacking EWSR1-rearrangements may remain unclassifiable. We retrospectively analyzed 41 Ewing-like tumors (formalin-fixed, paraffin-embedded) previously determined as negative or non-informative for EWSR1-rearrangements by FISH and/or RT-PCR. A new histopathology revision and additional IHC and molecular analyses were carried out in order to investigate whether additional IHC and/or molecular testing in combination with the morphological findings may help in reaching a definitive diagnosis. Almost all the tumors (n=40) involved soft tissue and/or bone and half the patients died of disease. In the archival cases all diagnoses were Ewing sarcoma (ES), Ewing-like sarcoma (ELS), myoepithelial tumor and undifferentiated sarcoma (US). In the new review all the tumors were re-classified as, ES (n=16), Ewing...

International Journal of Surgical Pathology

Eight conventional and six atypical oncocytomas in a series of 147 renal neoplasms were studied. ... more Eight conventional and six atypical oncocytomas in a series of 147 renal neoplasms were studied. Histopathologic findings revealed exclusively oncocytic cells, but cellular polymorphism was higher in the atypical tumors. Atypical oncocytomas presented focal necrosis, transcapsular invasion, or both. Electron microscopy showed similar findings in all cases. Immunohistochemistry of atypical oncocytomas had higher expression against proliferating cell nuclear antigen and more discontinuous immunostaining against laminin than typical ones. Flow cytometry revealed one or two aneuploid peaks in five typical and two atypical cases, although the latter had a higher proliferative fraction than typical oncocytomas. Cytogenetics of one typical oncocytoma showed a normal diploid karyotype; one atypical case resulted in a diploid karyotype but with endoreduplications in 13% of metaphases, and a second atypical oncocytoma became hypodiploid without structural anomalies. Based on the present resul...

Pathology - Research and Practice

Ewing sarcoma is an aggressive neoplasm of pediatric and adolescent patients. Immunohistochemistr... more Ewing sarcoma is an aggressive neoplasm of pediatric and adolescent patients. Immunohistochemistry (IHC) can be used to support the morphologic diagnosis of Ewing sarcoma family of tumors (ESFT) in a convincing clinical/radiological context. Although neither NKX2.2 nor CD99 alone are entirely specific, when combined, the diagnostic specificity is high. The aim of the present study was to investigate the IHC expression of NKX2.2, ETV4 and BCOR in a large series of genetically confirmed ESFT. The results for CD99 and CAV-1 immunoreactivity, and the histological and fusion gene subtypes were retrieved from our previous study. NKX2.2 demonstrated moderate or strong nuclear positivity in 91.2% of the tumors. The staining intensity was heterogeneous. Many of the ESFT with negative NKX2.2 immunoreactivity were in bone. Strong/moderate ETV4 nuclear expression was detected in two small round cell tumors, both were negative for NKX2.2. No relationships could be found between expression of NKX2.2 and the histological subgroups or ESFT gene fusion subtypes. BCOR was negative in all ESFT. In conclusion, NKX2.2, ETV4 and BCOR IHC may be helpful in daily practice for distinguishing ESFT from CIC or BCOR-associated sarcomas, especially in hospitals without access to molecular assays. In addition, the combination of strong CD99 membranous positivity and nuclear NKX2.2 positivity seems to be very reliable for ESFT diagnosis in an appropriate clinicoradiological setting. So far no antibody is entirely specific for ESFT diagnosis, and the IHC or molecular results in round cell tumors of bone may be strongly influenced by decalcification processes.