Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma

Our plain-English summary of Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma, by M. Miettinen, J. Limon, A. Niezabitowski, et al (The American Journal of Surgical Pathology, 2001).

The study

• Authors: M. Miettinen, J. Limon, A. Niezabitowski, J. Lasota
• Journal: The American Journal of Surgical Pathology
• Published: 2001;25(5):610-7
• Cited by: 113 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression. In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells. The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells. The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful.

In plain English

This laboratory study used antibody staining (immunohistochemistry) on stored tumor samples to compare synovial sarcoma with malignant mesothelioma. Synovial sarcoma is a soft-tissue cancer that can appear in the lung and pleura. The authors tested 103 synovial sarcomas (41 biphasic, 44 monophasic, 18 poorly differentiated) from a U.S. registry and two Polish institutions. They also tested 30 mesotheliomas (20 pleural, 10 peritoneal) and other sarcomas. Asbestos exposure was not studied. Calretinin, a protein used to identify mesothelioma, was found in 29 of 41 biphasic, 23 of 44 monophasic and 10 of 18 poorly differentiated synovial sarcomas, and in all 30 mesotheliomas. No synovial sarcoma tested was positive for WT1, while 12 of 17 epithelial mesotheliomas were. BerEp4 was positive in 27 of 30 biphasic synovial sarcomas but only focally in 3 of 23 epithelial mesotheliomas. Among the other sarcomas, only 2 of 15 malignant peripheral nerve sheath tumors showed calretinin. The authors concluded that calretinin cannot be used to separate mesothelioma from synovial sarcoma, and that differences in BerEp4, WT1 and certain keratins may help tell them apart.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemistry study of previously characterized tumor samples, comparing staining patterns across tumor types
• Who was studied: 103 synovial sarcomas (41 biphasic, 44 monophasic, 18 poorly differentiated) from the Armed Forces Institute of Pathology Soft Tissue Registry and from institutions in Gdansk and Krakow, Poland. These were compared with 30 diffuse mesotheliomas (20 pleural, 10 peritoneal; 23 epithelial, 7 sarcomatous). Other tumors tested for calretinin were 15 malignant peripheral nerve sheath tumors, 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, 20 angiosarcomas and 16 solitary fibrous tumors. No study dates are given.
• Exposure: No asbestos or other exposure was studied. The study tested tumor tissue with antibody stains for calretinin, HBME-1, BerEp4, CD15, CD141 (thrombomodulin), keratins 5/6, 7, 14 and 19, and Wilms tumor protein-1 (WT1). The only mention of asbestos is in the discussion, which refers to one previously reported cardiac synovial sarcoma from another publication.
• Main results:
  • Calretinin-positive tumor cells were found in 29 of 41 biphasic synovial sarcomas (71%). Positive cells were in the spindle cell component in 24 of 41 (59%) and in the epithelial component in 14 of 41 (34%).
  • Calretinin-positive tumor cells were found in 23 of 44 monophasic (52%) and 10 of 18 poorly differentiated (56%) synovial sarcomas.
  • All 23 epithelial mesotheliomas were calretinin positive, with most if not all tumor cells strongly positive. All 7 sarcomatoid mesotheliomas were also positive, ranging from focal to extensive.
  • HBME-1 was positive in all 28 biphasic synovial sarcomas tested and in 20 of 23 epithelial mesotheliomas. Sarcomatoid mesotheliomas were negative.
  • BerEp4 was positive in 27 of 30 biphasic synovial sarcomas (90%). Only 3 of 23 epithelial mesotheliomas had focal positivity, and all sarcomatoid mesotheliomas were negative.
  • WT1 was negative in all synovial sarcomas tested (18 biphasic, 31 monophasic, 11 poorly differentiated). It was detected in 12 of 17 epithelial mesotheliomas and in none of 4 sarcomatoid mesotheliomas tested.
  • CD141 was found in 20 of 21 epithelial mesotheliomas. In biphasic synovial sarcomas it was found in 7 of 20, limited to small foci in the spindle cell component.
  • Keratin 14 was prominent in the epithelial component of 39 of 44 biphasic synovial sarcomas (89%). It was found in 12 of 23 epithelial mesotheliomas, usually focally in scattered cells.
  • Keratins 7 and 19 were present in the majority of tumor cells in all mesotheliomas. In monophasic synovial sarcomas they were only focal (78% and 61% of cases had positive cells).
  • Among other sarcomas, 2 of 15 malignant peripheral nerve sheath tumors were focally calretinin positive. All solitary fibrous tumors, epithelioid sarcomas, leiomyosarcomas, gastrointestinal stromal tumors and angiosarcomas tested were negative.
• The authors' conclusion: The authors concluded that calretinin cannot be used to separate mesothelioma from synovial sarcoma, because both share calretinin and HBME-1 expression. They suggested that differences in BerEp4 and WT1, and focal versus global expression of keratins 7 and 19, may be helpful in telling the two apart. They also suggested that calretinin may be useful in distinguishing synovial sarcoma from other sarcomas.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Calretinin, Mesothelioma, Synovial Sarcoma, Malignant Mesothelioma, Neoplasm, Metastasis, Pleura, Epithelioid.

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• The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study — J. Ito, N. Asano, et al. (2016)
• Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma — C.E. Comin, L. Novelli, et al. (2001)
• E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma — M.P. Leers, M.M. Aarts, et al. (1998)
• Immunoreactivity for calretinin and keratins in desmoid fibromatosis and other myofibroblastic tumors: a diagnostic pitfall — S. Barak, Z. Wang, et al. (2012)

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