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

Our plain-English summary of 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, by M. Miettinen, M. Sarlomo-Rikala (The American Journal of Surgical Pathology, 2003).

The study

• Authors: M. Miettinen, M. Sarlomo-Rikala
• Journal: The American Journal of Surgical Pathology
• Published: 2003;27(2):150-8
• Cited by: 144 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Several immunohistochemical markers, among them calretinin, thrombomodulin (CD141), keratin 5, and mesothelin, have been documented or suggested as useful markers for positive identification of mesothelioma and to differentiate it from pulmonary adenocarcinoma; numerous studies have documented their variable specificity. However, expression of these markers in other types of lung carcinomas has not been systematically explored, although these tumors can enter in the differential diagnosis of mesothelioma. In this study we immunohistochemically evaluated 596 lung carcinomas of different types for the four above-mentioned mesothelioma markers, all of which reacted with a great majority of epithelioid mesotheliomas studied for comparison. Calretinin expression was common in giant cell carcinomas (67%), small cell carcinomas (49%), and large cell carcinomas (38%), whereas it was rare in usual adenocarcinomas but slightly more common in those with neuroendocrine differentiation (11% and 17%, respectively). Thrombomodulin was present in all keratinizing squamous carcinomas and the great majority (87%) of nonkeratinizing tumors in a membrane-staining pattern. It was moderately common in small cell (27%) and large cell carcinomas (25%) but relatively rare in adenocarcinomas (13%). Keratin 5 was expressed in all keratinizing and the great majority (87%) of nonkeratinizing squamous carcinomas, and a majority of large cell carcinomas (56%) and some small cell carcinomas (27%). It was rare in acinar adenocarcinomas (12%) and absent in those with neuroendocrine differentiation. Mesothelin was present in more than half (53%) of adenocarcinomas and a minority (13%) of large cell carcinomas but was absent in small cell carcinomas. In squamous carcinomas it was more often seen in nonkeratinizing versus keratinizing tumors (31% vs 16%). These results show that each of these "mesothelioma" markers reacts with different subsets of pulmonary carcinomas with a variable frequency; this should be considered when using these markers in the differential diagnosis of thoracic tumors.

In plain English

This laboratory study checked how often four stains used to help identify mesothelioma also stain lung cancers. The authors tested 596 surgically removed lung carcinomas collected at the University of Helsinki's Haartman Institute from 1974 to 2000. They compared them with 28 epithelioid mesotheliomas of the pleura. The article does not discuss asbestos exposure. Calretinin stained 4 of 6 giant cell carcinomas, 20 of 41 small cell carcinomas and 17 of 148 differentiated acinar adenocarcinomas. Thrombomodulin stained all 62 keratinizing squamous cell carcinomas and 13% of acinar adenocarcinomas. Keratin 5 stained 67 of 120 large cell carcinomas not otherwise specified (56%). Mesothelin stained 53% of differentiated acinar adenocarcinomas and none of the small cell carcinomas. Calretinin stained all but one mesothelioma, while thrombomodulin stained only 3 of 12 poorly differentiated mesotheliomas. The authors concluded that thrombomodulin should be used cautiously to tell lung carcinomas other than adenocarcinomas from mesothelioma, and that mesothelin has limited value here. They noted that keratin 5 and mesothelin lacked control cells present in every sample, though many samples had keratin 5 control cells.

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: Immunohistochemical (tissue staining) study of archived surgical tumor specimens, comparing lung carcinomas with pleural mesotheliomas
• Who was studied: 596 resected primary lung carcinomas of different types from the Haartman Institute, University of Helsinki, 1974 to 2000, plus 28 epithelioid pleural mesotheliomas from the same source for comparison
• Main results:
  • Calretinin was found in 4 of 6 giant cell carcinomas (67%), with 10 to 20% of tumor cells positive
  • Calretinin was found in 17 of 148 differentiated acinar-type adenocarcinomas (11%)
  • Thrombomodulin (CD141) was found in 13% of acinar adenocarcinomas; it was present in all keratinizing squamous cell carcinomas (62/62 in Table 3)
  • Keratin 5 was found in 67 of 120 large cell carcinomas not otherwise specified (56%); the text reports less positivity in large cell carcinomas with focal or extensive neuroendocrine differentiation (30% and 18%)
  • Mesothelin was found in 53% of differentiated acinar adenocarcinomas (78/148 in Table 5); all 41 small cell carcinomas were negative (Table 5)
  • In squamous cell carcinomas, mesothelin was more common in nonkeratinizing (31%) than keratinizing tumors (16%)
  • In the 28 epithelioid mesotheliomas, calretinin was positive in all but one
  • Thrombomodulin was positive in only 3 of 12 poorly differentiated solid epithelioid mesotheliomas (compared with 9 of 10 tubulopapillary ones)
  • Mesothelin was positive in 9 of 12 poorly differentiated epithelioid mesotheliomas
• The authors' conclusion: The authors concluded that thrombomodulin should be used with caution to distinguish lung carcinomas other than adenocarcinomas from mesothelioma, and that mesothelin also has limited value in this distinction
• Limitations the authors state:
  • Unlike calretinin and thrombomodulin, keratin 5 and mesothelin had no control cells present in every specimen to confirm the staining worked, although many cases showed keratin-5-positive bronchial basal cells and some showed mesothelin-positive cells
  • Totals varied slightly between markers because some sections were lost during processing or overdigested

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, Mesothelin, Carcinoma, Epithelioid, Mesothelioma, Pleura, Adenocarcinoma, Differential Diagnosis.

Related studies

• 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 — C.E. Comin, L. Novelli, et al. (2014)
• Immunoreactivity for calretinin and keratins in desmoid fibromatosis and other myofibroblastic tumors: a diagnostic pitfall — S. Barak, Z. Wang, et al. (2012)
• 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)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)
• Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma — G. Powell, H. Roche, et al. (2011)

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