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Vincent Caumette - One of the best experts on this subject based on the ideXlab platform.
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germline cdkn2a p16ink4a mutations contribute to genetic determinism of Sarcoma
Journal of Medical Genetics, 2017Co-Authors: Fanélie Jouenne, Isaure Chauvot De Beauchene, Emeline Bollaert, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Olivier Caron, Marie Françoise Avril, Philippe Terrier, Vincent CaumetteAbstract:BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue Sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with Sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a Sarcoma. Including the initial family, eight independent Sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded Sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As Sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION: Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary Sarcoma. In addition, we identified PDGFRA as a candidate modifier gene
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Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of Sarcoma
Journal of Medical Genetics, 2017Co-Authors: Fanélie Jouenne, Isaure Chauvot De Beauchene, Emeline Bollaert, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Olivier Caron, Marie Françoise Avril, Patrice Terrier, Vincent CaumetteAbstract:BACKGROUND Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue Sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with Sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a Sarcoma. Including the initial family, eight independent Sarcoma cases carried a germline mutation in the CDKN2A/p16(INK4A) gene. In five out of seven formalin-fixed paraffin-embedded Sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As Sarcomas are rare in CDKN2A/p16(INK4A) carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION Germline mutations in CDKN2A/P16(INK4A), a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary Sarcoma. In addition, we identified PDGFRA as a candidate modifier gene.
Jason L Hornick - One of the best experts on this subject based on the ideXlab platform.
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evaluation of etv4 and wt1 expression in cic rearranged Sarcomas and histologic mimics
Modern Pathology, 2016Co-Authors: Yin P Hung, Christopher D M Fletcher, Jason L HornickAbstract:A distinct subset of round cell Sarcomas harbors capicua transcriptional repressor (CIC) rearrangement. Diagnosing these Sarcomas can be difficult owing to their resemblance to Ewing Sarcoma and other 'small round blue cell tumors'; molecular techniques are generally required. Recent gene expression studies of CIC-rearranged Sarcomas identified the upregulation of ETV4. We assessed the sensitivity and specificity of ETV4 and WT1 immunohistochemistry for CIC-rearranged Sarcoma. We evaluated whole-tissue sections from 40 CIC-rearranged Sarcomas, 40 Ewing Sarcomas, 4 BCOR-CCNB3 Sarcomas, 6 unclassified round cell Sarcomas, and 150 histologic mimics. Moderate-to-strong nuclear immunoreactivity for ETV4 in at least 50% of cells was observed in 36 (90%) CIC-rearranged Sarcomas and 10 (5%) other tumors, including 5 unclassified round cell Sarcomas, 2 Wilms tumors, and 1 each desmoplastic small round cell tumor, melanoma, and small cell carcinoma. Thirty-eight (95%) CIC-rearranged Sarcomas showed nuclear staining for WT1, and 34 (85%) were positive for both ETV4 and WT1. Of 182 other tumors evaluated, 34 (19%) showed nuclear WT1 positivity, including all Wilms tumors and desmoplastic small round cell tumors, 5 unclassified round cell Sarcomas, and a subset of lymphoblastic lymphomas, rhabdomyoSarcomas, mesenchymal chondroSarcomas, carcinomas, and melanomas. In summary, diffuse moderate-to-strong ETV4 expression is present in most CIC-rearranged Sarcomas and unclassified round cell Sarcomas. More limited expression is seen in small subsets of various other round cell neoplasms. Nuclear WT1 expression is also present in most CIC-rearranged Sarcomas and unclassified round cell Sarcomas, along with Wilms tumors and desmoplastic small round cell tumors, and subsets of various histologic mimics. The sensitivity and specificity of diffuse ETV4 expression for CIC-rearranged Sarcomas are 90% and 95%, respectively, whereas the sensitivity and specificity of WT1 are 95% and 81%, respectively. Diffuse ETV4 along with at least focal WT1 expression is helpful to distinguish CIC-rearranged Sarcoma from Ewing Sarcoma and other histologic mimics.
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evaluation of nkx2 2 expression in round cell Sarcomas and other tumors with ewsr1 rearrangement imperfect specificity for ewing Sarcoma
Modern Pathology, 2016Co-Authors: Yin P Hung, Christopher D M Fletcher, Jason L HornickAbstract:Ewing Sarcoma shows considerable histologic overlap with other round cell tumors. NKX2-2, a homeodomain transcription factor involved in neuroendocrine/glial differentiation and a downstream target of EWSR1-FLI1, has been reported as an immunohistochemical marker for Ewing Sarcoma. We assessed the specificity of NKX2-2 for Ewing Sarcoma compared with other round cell malignant neoplasms and other soft tissue tumors with EWSR1 translocations. We evaluated whole-tissue sections from 270 cases: 40 Ewing Sarcomas (4 with atypical/large cell features), 20 CIC-DUX4 Sarcomas, 5 BCOR-CCNB3 Sarcomas, 9 unclassified round cell Sarcomas, 10 poorly differentiated synovial Sarcomas, 10 lymphoblastic lymphomas, 10 alveolar rhabdomyoSarcomas, 10 embryonal rhabdomyoSarcomas, 10 Merkel cell carcinomas, 10 small cell carcinomas, 20 melanomas, 5 NUT midline carcinomas, 10 Wilms tumors, 10 neuroblastomas, 10 olfactory neuroblastomas, 12 mesenchymal chondroSarcomas, 10 angiomatoid fibrous histiocytomas, 10 clear cell Sarcomas, 5 gastrointestinal clear cell Sarcoma-like tumors, 5 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondroSarcomas, 10 soft tissue and cutaneous myoepitheliomas, and 19 myoepithelial carcinomas. NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells. NKX2-2 was positive in 37/40 (93%) Ewing Sarcomas, including all atypical Ewing Sarcomas and cases with known EWSR1-FLI1 or EWSR1-ERG fusion; 85% of Ewing Sarcomas showed diffuse (>50%) staining. NKX2-2 was positive in 9 (75%) mesenchymal chondroSarcomas, 8 (80%) olfactory neuroblastomas, 1 CIC-DUX4 Sarcoma, 1 poorly differentiated synovial Sarcoma, 1 neuroblastoma, 2 unclassified round cell Sarcomas, and 3 small cell carcinomas; all other EWSR1-associated tumors were negative for NKX2-2, apart from 1 desmoplastic small round cell tumor, 1 myoepithelioma, and 1 myoepithelial carcinoma. In summary, NKX2-2 is a sensitive but imperfectly specific marker for Ewing Sarcoma. Nonetheless, NKX2-2 may be helpful to distinguish Ewing Sarcoma from some histologic mimics including CIC-DUX4 and BCOR-CCNB3 Sarcomas. Most other EWSR1-associated soft tissue tumors are negative for NKX2-2.
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evaluation of nkx2 2 expression in round cell Sarcomas and other tumors with ewsr1 rearrangement imperfect specificity for ewing Sarcoma
Modern Pathology, 2016Co-Authors: Yin P Hung, Christopher D M Fletcher, Jason L HornickAbstract:Ewing Sarcoma shows considerable histologic overlap with other round cell tumors. NKX2-2, a homeodomain transcription factor involved in neuroendocrine/glial differentiation and a downstream target of EWSR1-FLI1, has been reported as an immunohistochemical marker for Ewing Sarcoma. We assessed the specificity of NKX2-2 for Ewing Sarcoma compared with other round cell malignant neoplasms and other soft tissue tumors with EWSR1 translocations. We evaluated whole-tissue sections from 270 cases: 40 Ewing Sarcomas (4 with atypical/large cell features), 20 CIC-DUX4 Sarcomas, 5 BCOR-CCNB3 Sarcomas, 9 unclassified round cell Sarcomas, 10 poorly differentiated synovial Sarcomas, 10 lymphoblastic lymphomas, 10 alveolar rhabdomyoSarcomas, 10 embryonal rhabdomyoSarcomas, 10 Merkel cell carcinomas, 10 small cell carcinomas, 20 melanomas, 5 NUT midline carcinomas, 10 Wilms tumors, 10 neuroblastomas, 10 olfactory neuroblastomas, 12 mesenchymal chondroSarcomas, 10 angiomatoid fibrous histiocytomas, 10 clear cell Sarcomas, 5 gastrointestinal clear cell Sarcoma-like tumors, 5 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondroSarcomas, 10 soft tissue and cutaneous myoepitheliomas, and 19 myoepithelial carcinomas. NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells. NKX2-2 was positive in 37/40 (93%) Ewing Sarcomas, including all atypical Ewing Sarcomas and cases with known EWSR1-FLI1 or EWSR1-ERG fusion; 85% of Ewing Sarcomas showed diffuse (>50%) staining. NKX2-2 was positive in 9 (75%) mesenchymal chondroSarcomas, 8 (80%) olfactory neuroblastomas, 1 CIC-DUX4 Sarcoma, 1 poorly differentiated synovial Sarcoma, 1 neuroblastoma, 2 unclassified round cell Sarcomas, and 3 small cell carcinomas; all other EWSR1-associated tumors were negative for NKX2-2, apart from 1 desmoplastic small round cell tumor, 1 myoepithelioma, and 1 myoepithelial carcinoma. In summary, NKX2-2 is a sensitive but imperfectly specific marker for Ewing Sarcoma. Nonetheless, NKX2-2 may be helpful to distinguish Ewing Sarcoma from some histologic mimics including CIC-DUX4 and BCOR-CCNB3 Sarcomas. Most other EWSR1-associated soft tissue tumors are negative for NKX2-2.
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immunohistochemical staining for tle1 distinguishes synovial Sarcoma from histologic mimics
American Journal of Clinical Pathology, 2011Co-Authors: Wai Chin Foo, Michael W Cruise, Mark R Wick, Jason L HornickAbstract:Transducer-like enhancer of split 1 (TLE1) is overexpressed in synovial Sarcomas. We investigated TLE1 expression by immunohistochemical analysis in a well-characterized series of synovial Sarcomas and other mesenchymal tumors most commonly considered in the differential diagnosis. Whole tissue sections of 212 tumors were evaluated: 73 synovial Sarcomas (23 biphasic, 28 monophasic, 22 poorly differentiated), 47 malignant peripheral nerve sheath tumors (MPNSTs), 49 solitary fibrous tumors (SFTs), 20 fibroSarcomatous variants of dermatofibroSarcoma protuberans, and 23 Ewing Sarcomas/primitive neuroectodermal tumors (PNETs). All monophasic and poorly differentiated SSs and Ewing Sarcoma/PNETs were previously confirmed to harbor t(X;18) and EWSR1 gene rearrangements, respectively. In total, 60 (82%) of 73 synovial Sarcomas were positive for TLE1, including 18 biphasic (78%), 22 monophasic (79%), and 20 poorly differentiated (91%) tumors. Of the other tumors, only 7 MPNSTs (15%) and 4 SFTs (8%) were positive for TLE1, most of which showed only weak staining. TLE1 is a sensitive and specific marker for synovial Sarcoma and can be helpful to distinguish synovial Sarcoma from histologic mimics, particularly if moderate or strong staining is observed. In this study, only a small subset of MPNSTs and SFTs showed limited staining for TLE1.
Torsten O Nielsen - One of the best experts on this subject based on the ideXlab platform.
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ywhae fam22 endometrial stromal Sarcoma diagnosis by reverse transcription polymerase chain reaction in formalin fixed paraffin embedded tumor
Human Pathology, 2013Co-Authors: Anna Isphording, Lien N Hoang, Julie A Irving, Angela Goytain, Nataliya Nelnyk, Torsten O Nielsen, David G Huntsman, Blake C GilksAbstract:Summary A subset of endometrial stromal Sarcoma harbors t(10;17)(q23;p13), which results in the genetic fusion between YWHAE and 1 of 2 highly homologous FAM22 family members— FAM22A or FAM22B . In contrast to classic low-grade endometrial stromal Sarcoma with JAZF1-SUZ12 fusions, YWHAE-FAM22 endometrial stromal Sarcoma displays high-grade histologic features and is associated with more aggressive disease course. Ancillary fluorescence in situ hybridization assay demonstrating the presence of YWHAE rearrangement can be used to support the diagnosis, but the detection of fusion transcript would be the most definitive test. We describe here an optimized reverse transcription–polymerase chain reaction assay for detection of YWHAE-FAM22 fusion transcript in formalin-fixed and paraffin-embedded tumor samples. We studied a series of 6 YWHAE-FAM22 endometrial stromal Sarcomas, 7 JAZF-SUZ12 endometrial stromal Sarcomas, 3 JAZF1-PHF1/EPC1-PHF1 endometrial stromal Sarcomas, 6 undifferentiated endometrial Sarcomas, 4 uterine leiomyoSarcomas, and 4 uterine adenoSarcomas. All 6 YWHAE-FAM22 endometrial stromal Sarcomas were confirmed by fluorescence in situ hybridization assay, whereas all non– YWHAE-FAM22 tumors were confirmed to lack YWHAE rearrangement by fluorescence in situ hybridization assay. The reverse transcription–polymerase chain reaction assay optimized for formalin-fixed and paraffin-embedded samples detected YWHAE-FAM22 fusion transcripts in all 6 YWHAE-FAM22 endometrial stromal Sarcomas and none of the 24 non– YWHAE-FAM22 uterine Sarcomas. These findings show that this reverse transcription–polymerase chain reaction assay is sensitive and specific for detection of YWHAE-FAM22 fusion transcript and can serve as a useful adjunct diagnostic assay to confirm the diagnosis of YWHAE-FAM22 endometrial stromal Sarcoma in formalin-fixed and paraffin-embedded tumor samples.
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tissue microarray validation of epidermal growth factor receptor and sall2 in synovial Sarcoma with comparison to tumors of similar histology
American Journal of Pathology, 2003Co-Authors: Torsten O Nielsen, Blake C Gilks, John X Oconnell, Poul H B Sorensen, Sabine C Linn, Robert B West, David Botstein, Patrick O Brown, Matt Van De RijnAbstract:Histological diagnosis of synovial Sarcoma can be difficult. Genome-wide expression profiling has identified a number of genes expressed at higher levels in synovial Sarcoma than in other soft tissue tumors, representing excellent candidates for diagnostic immunohistochemical markers. A tissue microarray comprising 77 Sarcomas, including 46 synovial Sarcomas, was constructed to validate identified markers and investigate their expression in tumors in the differential diagnosis of synovial Sarcoma. Immunostaining was performed for two such markers, epidermal growth factor receptor and SAL (drosophila)-like 2 (SALL2), and for fifteen established markers used in the differential diagnosis of Sarcomas. As predicted by expression profiling, epidermal growth factor receptor (a potential therapeutic target) and SALL2 stained most cases of synovial Sarcoma; staining was significantly less common among other tested Sarcomas. Hierarchical clustering analysis applied to immunostaining results for all 18 antibodies showed that synovial Sarcomas, leiomyoSarcomas, hemangiopericytomas, and solitary fibrous tumors cluster distinctly, and assigned one case with indeterminate histology as a Ewing Sarcoma. Digital images from over 2500 immunostained cores analyzed in this study were captured and are made accessible through the accompanying website: http://microarray-pubs.stanford.edu/tma_portal/synsarc.
Fanélie Jouenne - One of the best experts on this subject based on the ideXlab platform.
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germline cdkn2a p16ink4a mutations contribute to genetic determinism of Sarcoma
Journal of Medical Genetics, 2017Co-Authors: Fanélie Jouenne, Isaure Chauvot De Beauchene, Emeline Bollaert, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Olivier Caron, Marie Françoise Avril, Philippe Terrier, Vincent CaumetteAbstract:BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue Sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with Sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a Sarcoma. Including the initial family, eight independent Sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded Sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As Sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION: Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary Sarcoma. In addition, we identified PDGFRA as a candidate modifier gene
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Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of Sarcoma
Journal of Medical Genetics, 2017Co-Authors: Fanélie Jouenne, Isaure Chauvot De Beauchene, Emeline Bollaert, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Olivier Caron, Marie Françoise Avril, Patrice Terrier, Vincent CaumetteAbstract:BACKGROUND Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue Sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with Sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a Sarcoma. Including the initial family, eight independent Sarcoma cases carried a germline mutation in the CDKN2A/p16(INK4A) gene. In five out of seven formalin-fixed paraffin-embedded Sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As Sarcomas are rare in CDKN2A/p16(INK4A) carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION Germline mutations in CDKN2A/P16(INK4A), a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary Sarcoma. In addition, we identified PDGFRA as a candidate modifier gene.
Markku Miettinen - One of the best experts on this subject based on the ideXlab platform.
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erg expression in epithelioid Sarcoma a diagnostic pitfall
The American Journal of Surgical Pathology, 2013Co-Authors: Markku Miettinen, Zengfeng Wang, Ziedulla Abdullaev, Svetlana Pack, Maarit Sarlomorikala, John F. FetschAbstract:ERG transcription factor is constitutively expressed in endothelial cells. Because benign and malignant vascular endothelia retain the ERG-expression, ERG is considered a useful marker for angioSarcomas and related tumors. ERG is also expressed in a subset of prostate carcinomas and Ewing Sarcomas due to ERG-involving translocations, so that this marker is also of high interest for the study of these malignancies. In this study, we evaluated 109 epithelioid Sarcomas for ERG expression, based on an initial observation of an ERG-positive case. We also studied expression of other endothelial antigens in epithelioid Sarcoma. ERG was expressed in 38% of epithelioid Sarcomas (41/109), usually with a uniform nuclear staining, similar to that seen in angioSarcomas. However, all epithelioid Sarcomas were negative for ERG gene rearrangement indicating that that ERG expression is not likely related to ERG involving translocations in epithelioid Sarcoma. Other endothelial markers, CD31, claudin 5, and Prox1 were absent in epithelioid Sarcomas. The only exception was a pulmonary metastasis of epithelioid Sarcoma showing focal CD31 expression, which was probably resulting from antigen adsorption onto tumor cell surfaces. However, podoplanin was commonly (7/9) expressed in epithelioid Sarcoma, so that this marker is not useful in the distinction of epithelioid Sarcoma and angioSarcoma. INI1/SMARCB1 gene product was absent in all epithelioid Sarcomas (considered here a definitional feature) but was absent from only one epithelioid angioSarcoma, indicating its relative specificity for epithelioid Sarcoma in this differential diagnostic setting. ERG expression is fairly common in epithelioid Sarcoma, and should be recognized as a diagnostic pitfall in the differential diagnosis of epithelioid Sarcoma and epithelioid angioSarcoma. General lack of endothelial cell specific markers in epithelioid Sarcoma helps in this distinction.
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ny eso 1 expression in synovial Sarcoma and other mesenchymal tumors significance for ny eso 1 based targeted therapy and differential diagnosis
Modern Pathology, 2012Co-Authors: Paul F Robbins, Mark Raffeld, Phyu P Aung, Maria Tsokos, Steven A Rosenberg, Markku MiettinenAbstract:A promising targeted therapy against NY-ESO-1 (CTAG 1B) using genetically modified T-cells in synovial Sarcomas was recently demonstrated in a clinical trial at the NCI. To investigate the role of NY-ESO-1 immunohistochemistry in patient selection and gain better insight into the incidence of NY-ESO-1 expression in synovial Sarcomas and other mesenchymal tumors, we evaluated NY-ESO-1 expression by immunohistochemistry in 417 tumors. This collection of samples included: 50 SS18/SSX1/2 fusion positive synovial Sarcomas, 155 gastrointestinal stromal tumors (GIST), 135 other spindle cell Sarcomas as well as 77 other Sarcomas (chondroSarcoma, osteoSarcoma, dedifferentiated lipoSarcoma, alveolar soft part Sarcoma, rhabdomyoSarcoma, angioSarcoma, malignant mesothelioma, and Ewing's Sarcoma). We report that 76% of synovial Sarcomas expressed NY-ESO-1 in a strong and diffuse pattern (2−3+, >50–70% of tumor cells). In contrast, only rare cases of other spindle cell mesenchymal tumor expressed NY-ESO-1 (GIST (2/155), malignant peripheral nerve sheath tumors (1/34), and dermatofibroSarcoma protuberans (2/20)). Individual cases of other Sarcomas (angioSarcoma, malignant mesothelioma, chondroSarcoma, osteoSarcoma, dedifferentiated lipoSarcoma, alveolar soft part Sarcoma, and Ewing's Sarcoma) were positive for NY-ESO-1. However, no positive cases were identified amongst our cohort of leiomyoSarcomas (0/24), hemangiopericytoma/solitary fibrous tumors (0/40), and cellular schwannomas (0/17). In summary, we find that NY-ESO-1 is strongly and diffusely expressed in a majority of synovial Sarcomas, but only rarely in other mesenchymal lesions. Beyond its role in patient selection for targeted therapy, immunohistochemistry for NY-ESO-1 may be diagnostically useful for the distinction of synovial Sarcoma from other spindle cell neoplasms.
