Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma

Our plain-English summary of Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma, by L. Zuccatosta, T. Bizzarro, G. Rossi, et al (Diagnostics, 2023).

The study

• Authors: L. Zuccatosta, T. Bizzarro, G. Rossi, G. Gallo, S. Gasparini, A. Ambrosini-Spaltro
• Journal: Diagnostics
• Published: 2023;13(2)
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.

In plain English

This laboratory study tested whether two tissue stains, Claudin-4 and BAP1, can tell sarcomatoid mesothelioma apart from sarcomatoid carcinoma, a cancer that can look similar under the microscope. The authors examined 41 pleural biopsies of sarcomatoid mesothelioma, 46 surgically removed sarcomatoid carcinomas from various organs (most often the lung), and 49 pleural biopsies of normal or benign reactive mesothelium as controls. Claudin-4 appeared in the sarcomatous part of 18 of 46 carcinomas (39.1%). Counting the epithelial part of mixed tumors as well, it appeared in 30 of 46 (65.2%). It appeared in none of the 41 mesotheliomas. BAP1 was lost in 23 of 41 mesotheliomas (56.1%). It was lost in none of the carcinomas and none of the control samples. Both markers showed 100% specificity in this series. As a limitation, the authors noted that the mesotheliomas were biopsies while the carcinomas were surgical specimens. The authors concluded that Claudin-4 helps favor sarcomatoid carcinoma and that BAP1 loss is very specific for sarcomatoid mesothelioma. The article did not report asbestos exposure.

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: Diagnostic laboratory (immunohistochemistry) study of archived tissue samples, described as retrospective and prospective
• Who was studied: Cases from 2006 to 2021: 41 surgical pleural biopsies of sarcomatoid mesothelioma (28 purely sarcomatoid, 13 desmoplastic) and 46 surgical resections of sarcomatoid carcinoma (27 biphasic, 19 monophasic). Of the carcinomas, 18 came from the lung and 28 from eight other primary sites (kidney, bladder, skin, pancreas, endometrium, colon, breast, cervix). A control group of 49 pleural biopsies of normal or benign reactive mesothelium was also studied.
• Exposure: Not reported. The study tested two laboratory stains (Claudin-4 and BAP1) on tumor tissue; it gives no information on patients' asbestos or other exposures.
• Main results:
  • Sarcomatoid carcinomas, sarcomatous component only: Claudin-4 was expressed in 18 of 46 (39.1%). Sarcomatoid mesotheliomas: Claudin-4 was expressed in none of the 41.
  • Sarcomatoid carcinomas, counting all tumor components: Claudin-4 was expressed in 30 of 46 (65.2%).
  • Monophasic sarcomatoid carcinomas: Claudin-4 was expressed in 3 of 19 (15.8%), all focally.
  • Biphasic sarcomatoid carcinomas: Claudin-4 was expressed in the sarcomatous component of 15 of 27 (55.6%) and in the carcinomatous component of all 27 of 27 (100%).
  • All sarcomatoid carcinomas kept BAP1 staining (no BAP1 loss).
  • Sarcomatoid mesotheliomas were all Claudin-4 negative. BAP1 was lost in 23 of 41 (56.1%): 15 of 28 (53.6%) purely sarcomatoid and 8 of 13 (61.5%) desmoplastic mesotheliomas.
  • All 14 normal mesothelium samples and all 35 reactive mesothelial proliferation samples kept BAP1 and were negative for Claudin-4.
  • For detecting sarcomatoid mesothelioma, BAP1 loss had 56.1% sensitivity and 100% specificity.
  • For detecting sarcomatoid carcinoma, Claudin-4 in all components had 65.2% sensitivity and 100% specificity.
  • For detecting sarcomatoid carcinoma, Claudin-4 in the sarcomatous component only had 39.1% sensitivity and 100% specificity (41/41 in Table 3).
• The authors' conclusion: The authors concluded that Claudin-4 expression appears helpful to favor sarcomatoid carcinoma and exclude sarcomatoid mesothelioma, and that BAP1 loss remains a very specific finding for identifying sarcomatoid mesothelioma.
• Limitations the authors state:
  • The samples differed in type and origin: the mesotheliomas were pleural biopsies, while the carcinomas were surgical specimens from different primary organs.

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Claudin-4, BAP1, Differential Diagnosis, Sarcomatoid, Carcinoma, Mesothelioma, Epithelioid.

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