Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma

Our plain-English summary of Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma, by C.E. Comin, L. Novelli, A. Cavazza, et al (Tumori, 2014).

The study

• Authors: C.E. Comin, L. Novelli, A. Cavazza, M. Rotellini, F. Cianchi, L. Messerini
• Journal: Tumori
• Published: 2014;100(5):559-67
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims And Background: A number of immunohistochemical markers have been suggested as useful in the positive diagnosis of epithelioid mesothelioma. The most widely used mesothelioma markers are thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1. Numerous investigations have demonstrated their variable sensitivity and specificity in differentiating epithelioid mesothelioma from lung adenocarcinoma. However, data on the expression of these markers in other types of lung carcinomas are very limited. We evaluated the expression of these markers in a series of 172 primary carcinomas of the lung and in 75 epithelioid pleural mesotheliomas.

Results: Thrombomodulin expression was found in squamous cell carcinomas (71%), small cell lung carcinomas (11%), adenocarcinomas (4%), large cell carcinomas (50%), large cell neuroendocrine carcinomas (25%) and in sarcomatoid carcinomas (10%). Calretinin expression was common in small cell lung carcinomas (44%) and large cell neuroendocrine carcinomas (25%), less common in squamous cell carcinomas (20%), rare and focal in adenocarcinomas (4%) and sarcomatoid carcinomas (10%). Cytokeratin 5/6 was expressed in most of the squamous cell carcinomas (94.5%). Immunoreactivity was also found in large cell carcinomas (50%), sarcomatoid carcinomas (30%) and rarely in adenocarcinomas (4%). D2-40 was consistently expressed in squamous cell carcinomas (42%). Focal immunoreactivity was found in adenocarcinomas (3%). WT-1 was focally present in one (2%) squamous cell carcinoma.

Conclusions: These results indicate that some of the most commonly used mesothelioma markers may react with different types of primary lung carcinomas. These data should be taken into consideration especially when dealing with small biopsy fragments and poorly differentiated tumors.

In plain English

This was a laboratory study of stored tumor tissue at the University of Florence, Italy. The authors stained 172 primary lung carcinomas and 75 epithelioid pleural mesotheliomas with five markers used to help recognize mesothelioma: thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1. Asbestos exposure was not studied. In the mesotheliomas, calretinin stained all 75 cases, D2-40 73 (97%), cytokeratin 5/6 70 (93%), WT-1 67 (89%) and thrombomodulin 58 (77%). Several markers also stained lung cancers. Among 55 squamous cell carcinomas, cytokeratin 5/6 was positive in 94.5%, thrombomodulin in 39 (71%), D2-40 in 23 (42%) and calretinin in 11 (20%). Calretinin stained 8 of 18 small cell carcinomas (44%). Among 71 adenocarcinomas, staining was rare (no more than 3 cases for any marker) and focal. WT-1 stained only one lung cancer, a squamous cell carcinoma. The authors concluded that these markers may react with different types of lung carcinoma and that WT-1 seemed the most specific mesothelioma marker. They noted that some tumor groups were too small to draw conclusions from.

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: Retrospective laboratory (immunohistochemical) study of archived tumor cases
• Who was studied: Tumor tissue from the Division of Pathological Anatomy, University of Florence, Italy. There were 172 primary lung carcinomas: 55 squamous cell carcinomas, 71 adenocarcinomas, 18 small cell carcinomas, 4 large cell carcinomas, 4 large cell neuroendocrine carcinomas, 10 sarcomatoid carcinomas and 10 carcinoid tumors. For comparison there were 75 epithelioid pleural mesotheliomas from the same source. Dates were not given.
• Exposure: Not applicable. No asbestos or other exposure was assessed. The tumors were stained with five antibody markers: thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1.
• Main results:
  • In the 75 epithelioid pleural mesotheliomas, calretinin was positive in all cases.
  • In the mesotheliomas, D2-40 was positive in 73 (97%).
  • In the mesotheliomas, WT-1 was positive in 67 (89%).
  • In the mesotheliomas, cytokeratin 5/6 was positive in 70 (93%).
  • In the mesotheliomas, thrombomodulin was positive in 58 (77%).
  • In squamous cell lung carcinomas, thrombomodulin was positive in 39 (71%) of 55 cases.
  • Cytokeratin 5/6 was positive in 94.5% of squamous cell lung carcinomas.
  • D2-40 was positive in 23 (42%) of 55 squamous cell lung carcinomas.
  • Calretinin was positive in 8 (44%) of 18 small cell lung carcinomas.
  • Among 71 adenocarcinomas, thrombomodulin, calretinin and cytokeratin 5/6 were each positive in 3 (4%), with focal staining. D2-40 was positive in 2 (3%) and WT-1 in none (Table 2).
  • WT-1 was positive (focally) in only one lung carcinoma, a squamous cell carcinoma (2% of squamous cases).
• The authors' conclusion: The authors concluded that these markers may react with different types of primary lung carcinoma at variable frequency. In their view, thrombomodulin, cytokeratin 5/6 and D2-40 especially in squamous cell carcinomas, and calretinin in high-grade neuroendocrine carcinomas. They considered WT-1 the most specific positive mesothelioma marker.
• Limitations the authors state:
  • The authors said the number of large cell carcinomas (4 cases) was too small to draw conclusions from.

Topics

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

Medical terms in this study, explained in our Lexicon: Calretinin, Cytokeratin 5/6, Podoplanin (D2-40), Wilms Tumor 1 (WT-1), Carcinoma, Epithelioid, Pleural Mesothelioma, Mesothelioma.

Related studies

• Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura — M. Miettinen, M. Sarlomo-Rikala (2003)
• 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)
• Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura — P.M. Cury, D.N. Butcher, et al. (2000)
• The diagnostic utility of D2-40, calretinin, CK5/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology — T.S. Hyun, M. Barnes, et al. (2012)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)
• p40 is the best marker for diagnosing pulmonary squamous cell carcinoma: comparison with p63, cytokeratin 5/6, desmocollin-3, and sox2 — T. Tatsumori, K. Tsuta, et al. (2014)

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