Immunophenotype of Desmoplastic Small Round Cell Tumors as Detected in Cases with EWS-WT1 Gene Fusion Product

Zhang, Paul J.; Goldblum, John R.; Pawel, Bruce; Fisher, Cyril; Pasha, Theresa L.; Barr, Frederic G.

doi:10.1097/01.mp.0000056630.76035.f3

Cited by 138 publications

(91 citation statements)

References 27 publications

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“…34 In contrast to mesotheliomas, however, DSRCTs can express some markers, such as MOC-31, Ber-EP4, and TAG-72, which are almost invariably absent in mesotheliomas. 38,39 Similar to mesotheliomas, although, DSRCTs are often positive for WT1 29,38,40,41 and mesothelin. 32 A main feature of DSRCT is the common expression of desmin in a globoid-like staining pattern.…”

Section: Discussionmentioning

confidence: 99%

Mesotheliomas with small cell features: report of eight cases

Ordóñez

2012

Modern Pathology

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Mesotheliomas with small cell morphology are rare and only one study of such cases has been published. As a result of their rare occurrence, some investigators have cast doubt on the existence of such a histologic variant of mesothelioma. This investigator reports a series of eight cases of epithelioid mesothelioma with small cell features, all of which originated in the pleura. Seven of the patients were men and one was a woman. Four patients had a history of asbestos exposure. Histologically, four of the mesotheliomas were epithelioid and four biphasic. The proportion of small cells seen in these cases constituted 80 to 100% of the tumor included in the biopsy material and 15 to 20% of the tumor present in the pneumonectomy specimens. Immunoreactivity for calretinin, keratin 5/6, keratin 7, pan-keratin, WT1, podoplanin, and mesothelin was seen in all cases tested for these markers. All of the cases were negative for MOC-31, Ber-EP4, CEA, CD15, TAG-72, TTF-1, chromogranin A, synaptophysin, CD99, and desmin. The mean survival of the six patients for whom this information was available was 8.2 months. It is important for pathologists to be aware that mesotheliomas can present small cell features and, because of this, they can be confused with other malignancies that can exhibit similar morphology. The value of immunohistochemistry in the differential diagnosis of these tumors is discussed.

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Section: Discussionmentioning

confidence: 99%

Mesotheliomas with small cell features: report of eight cases

Ordóñez

2012

Modern Pathology

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“…21 An expanded panel of immunohistochemical markers is extremely helpful in this diagnostic setting, but nonetheless suffers from variable degrees of insufficient specificities, lack of general availability, and/or technical/interpretive difficulties. [24][25][26][27][28][29][30][31] Therefore, the development of molecular diagnostic techniques for the detection of relatively unique fusion transcripts present within subtypes of round cell tumors has proven to be a helpful adjunct. However, the reliability of various diagnostic techniques in routine formalin-fixed paraffin-embedded tissue has not been fully explored, especially for those such as the EWS FISH break apart approach, for which DNA probes have only recently become commercially available.…”

Section: Discussionmentioning

confidence: 99%

Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: a comparison of two FISH strategies and RT-PCR in malignant round cell tumors

et al. 2006

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Ewing sarcoma/primitive neuroectodermal tumor (EWS/PNET) is a diagnostically challenging malignant round cell tumor with signature translocations involving the EWS gene. These translocations are detectable with both reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded tissue. However, RT-PCR is less sensitive in formalin-fixed paraffinembedded than frozen tissue. Similarly, commercial FISH probes have recently become available, but have yet to be rigorously tested in the clinical setting. Therefore, we have compared RT-PCR with FISH using 'home brew' fusion probes for Ewing sarcoma (EWS)-FLI1 and a commercial EWS break apart probe set in 67 archival round cell tumors, including 27 EWS/PNETs. Sensitivities and specificities for both FISH assays were 91 and 100%, respectively, whereas RT-PCR had a sensitivity of 54% and a specificity of 85%. The break apart strategy was easier to interpret than probe fusion approach. We conclude that FISH is a more sensitive and reliable ancillary technique than RT-PCR for the diagnosis of EWS/PNET in formalin-fixed paraffin-embedded tissue, although the latter provides additional information regarding fusion transcript subtype and prognosis. The commercial break apart probe set is both readily available and easy to interpret, making it particularly attractive. Nonetheless, complex round cell tumors often benefit from molecular testing with multiple methods.

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“…In humans, Mb is synthesised at concentrations of B200 -300 mM in striated muscle and, although at much lower levels, in a variety of human tumours including medullomyoblastoma (Smith and Davidson, 1984), thymolipoma (Iseki et al, 1990), acute leukaemia (Ruck et al, 1995) and desmoplastic small round cell tumours (Zhang et al, 2003). Following an accidentalobservation of positive Mb staining in several human carcinomas in 2001, we have systematically examined Mb expression in human breast cancer.…”

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confidence: 99%

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

et al. 2010

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BACKGROUND: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. METHODS: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-a (ERa)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1a (HIF-1a), HIF-2a, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERa or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. RESULTS: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2a and CAIX, but not to HIF-1a or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERa or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. CONCLUSION: We conclude that in breast cancer, Mb is co-expressed with ERa and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

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Immunophenotype of Desmoplastic Small Round Cell Tumors as Detected in Cases with EWS-WT1 Gene Fusion Product

Cited by 138 publications

References 27 publications

Mesotheliomas with small cell features: report of eight cases

Mesotheliomas with small cell features: report of eight cases

Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: a comparison of two FISH strategies and RT-PCR in malignant round cell tumors

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

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