Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma

Our plain-English summary of Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma, by G. Powell, H. Roche, W.R. Roche (Histopathology, 2011).

The study

• Authors: G. Powell, H. Roche, W.R. Roche
• Journal: Histopathology
• Published: 2011;59(5):950-6
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Calretinin and cytokeratin (CK)5/6 are frequently used to differentiate between metastatic breast cancer and primary malignant mesothelioma in pleural biopsies, but both tumours may express these markers. This study was aimed at evaluating the frequency of calretinin expression in primary breast carcinomas, and assessing the characteristics of the calretinin-positive tumours.

Methods And Results: Fifty-three primary breast adenocarcinomas were analysed for immunohistochemical expression of calretinin. CK5/6 and epidermal growth factor receptor (EGFR) immunostaining were performed on the calretinin-positive subset. Tumours were classified as basal-like if they met standard morphological and immunohistochemical criteria. Fifteen per cent (8/53) of the breast tumours were positive for calretinin. Eighty-eight per cent (7/8) of the calretinin-positive tumours were grade 3, as compared with 20% (9/45) of the calretinin-negative tumours (P<0.001). Only 13% (1/8) of the calretinin-positive tumours were also oestrogen receptor (ER)-positive, as compared with 87% (39/45) of the calretinin-negative tumours (P<0.001). Eleven per cent (6/53) of the tumours were classified as basal-like. Of these, four were positive for calretinin and two were negative (P=0.003).

Conclusions: Fifteen per cent of breast carcinomas stain with calretinin. These tumours are more likely to be high-grade, ER-negative, and display a basal-like phenotype. These tumours may be misdiagnosed as malignant mesothelioma when they metastasize to the pleura.

© 2011 Blackwell Publishing Limited.

In plain English

This laboratory study from Southampton, UK, tested whether breast cancers can stain positive for calretinin. Pathologists often use this marker to help tell pleural mesothelioma apart from cancer that has spread to the pleura from elsewhere. The authors stained 53 randomly selected archived breast adenocarcinomas from 2002 to 2003. Eight of the 53 (15%) were calretinin-positive. Seven of those 8 were grade 3, compared with 9 of the 45 calretinin-negative tumours (P = 0.00049). Only 1 of the 8 calretinin-positive tumours was oestrogen receptor (ER)-positive, compared with 39 of the 45 calretinin-negative tumours. Six tumours were classed as basal-like, and four of these were calretinin-positive. In a review of pleural biopsies from women, none of 29 breast cancers that had spread to the pleura showed calretinin staining. Of the 15 pleural biopsies from women diagnosed as malignant mesothelioma, two came from patients with recorded breast cancer histories but no history of asbestos exposure. The authors said only that some such breast tumours could possibly have been misdiagnosed as mesothelioma. The study did not measure asbestos exposure. The authors concluded that such breast tumours may be misdiagnosed as malignant mesothelioma when they spread to the pleura.

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 randomly selected archived breast cancer specimens, plus a retrospective audit of pleural biopsies
• Who was studied: 53 primary invasive breast adenocarcinomas randomly selected from the pathology archive of Southampton General Hospital, UK (1 October 2002 to the date printed as 31 September 2003); also malignant-coded pleural biopsies from women, 2001 to 2005
• Exposure: No asbestos exposure was studied. The study looked at tumour staining for calretinin (all cases), with CK5/6 and EGFR staining in calretinin-positive or possibly basal-like tumours, alongside ER, PR and HER2 status
• Main results:
  • 8 of 53 breast carcinomas (15%) were positive for calretinin (five strongly, three weakly); the other 45 were negative
  • Grade 3 tumours: 7 of 8 (88%) calretinin-positive tumours versus 9 of 45 (20%) calretinin-negative tumours (P = 0.00049)
  • ER-positive tumours: 1 of 8 (13%) calretinin-positive tumours versus 39 of 45 (87%) calretinin-negative tumours (P = 0.000079)
  • 7 of the 53 tumours (13%) were both calretinin-positive and ER-negative
  • Of the 6 tumours classed as basal-like, 4 were calretinin-positive and 2 were calretinin-negative (P = 0.003)
  • In the pleural biopsy audit, none of the 29 breast cancers diagnosed as having spread to the pleura showed calretinin staining
  • In the audit period, 15 pleural biopsies from women were diagnosed as malignant mesothelioma
  • Of these 15 women diagnosed with malignant mesothelioma, two had recorded histories of breast cancer but no history of asbestos exposure
  • The authors stated only that, given their findings, there was a possibility that some tumours with this staining profile had been misdiagnosed as epithelioid malignant mesothelioma
• The authors' conclusion: The authors concluded that calretinin-positive breast tumours, which were more likely to be high-grade, ER-negative and basal-like, may be misdiagnosed as malignant mesothelioma when they metastasize to the pleura
• Limitations the authors state:
  • The authors stated that the small sample size may explain why their share of basal-like tumours (11%) was lower than the generally accepted 16 to 19%

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, Carcinoma, Misdiagnosis, Mesothelioma, Malignant Mesothelioma, Adenocarcinoma, EGFR, Metastasis.

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)
• 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)
• 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)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)
• Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study — N.G. Ordóñez, A.A. Sahin (2014)
• Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung — Y. Hattori, A. Yoshida, et al. (2015)

Browse more research in Histopathology, or return to medical research.