Carbonic anhydrase IX (CAIX) does not differentiate between benign and malignant mesothelium

Our plain-English summary of Carbonic anhydrase IX (CAIX) does not differentiate between benign and malignant mesothelium, by V. Ananthanarayanan, M. Tretiakova, A.N. Husain, et al (American Journal of Clinical Pathology, 2014).

The study

• Authors: V. Ananthanarayanan, M. Tretiakova, A.N. Husain, T. Krausz, T. Antic
• Journal: American Journal of Clinical Pathology
• Published: 2014;142(1):82-7
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: To examine carbonic anhydrase IX (CAIX), a marker of renal cell carcinoma that recently has been described in malignant effusions.

Methods: Pleural and peritoneal fluids with the following diagnoses-reactive (n = 23), carcinoma (n = 17), and "suspicious for mesothelioma" (n = 4)-were immunostained for CAIX, calretinin, Ber-EP4, and MOC31. A tissue microarray of epithelioid (n = 27) and sarcomatoid (n = 8) mesotheliomas and three cases of benign mesothelium were also immunostained for CAIX.

Results: Mesothelial cells in both reactive (18/23) and malignant effusions (18/21) were positive for CAIX (P > .05). In carcinomatous effusions, CAIX expression was restricted to the mesothelial cells. Agreement between CAIX and calretinin expression was present in 89% of cases. In tissues, CAIX was positive in 100% of benign and 91% of malignant mesothelium.

Conclusions: CAIX can be a useful ancillary marker for identifying mesothelial cells. There is no difference in CAIX expression between benign and malignant mesothelium. Caution should be exercised while evaluating for metastasis from renal cell carcinoma.

Copyright© by the American Society for Clinical Pathology.

In plain English

This laboratory study, which did not examine asbestos exposure, tested whether the marker carbonic anhydrase IX (CAIX) distinguishes reactive (benign) mesothelial cells from malignant cells. The authors stained archived University of Chicago fluid samples (2010 to 2012). These were mostly pleural and peritoneal fluids, plus pelvic washings and one pericardial fluid (23 reactive, 17 carcinoma, 4 suspicious for mesothelioma). They also stained tissue from 27 epithelioid and 8 sarcomatoid mesotheliomas, and 3 benign hernia sacs. CAIX staining was present in 18 of 23 reactive and 18 of 21 malignant fluids. Staining scores did not differ (P = .49). In the fluids, only mesothelial cells stained, not carcinoma cells. Scored only as present or absent, CAIX agreed with calretinin, a mesothelial marker, in 89% of cases, but its staining scores were much lower. In tissue, CAIX stained 26 of 27 epithelioid and 6 of 8 sarcomatoid mesotheliomas, and all three hernia sacs. The authors concluded that CAIX marks mesothelial cells whether benign or malignant. They warned that relying on CAIX alone to support renal cell carcinoma in fluids could be a serious pitfall. No fluids with metastatic renal cell carcinoma were included.

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 (immunohistochemistry) study of archived cytology cell blocks and a mesothelioma tissue microarray
• Who was studied: Fluid samples from the University of Chicago, 2010 to 2012. These were pleural and peritoneal fluids and pelvic washings, plus one pericardial fluid. They comprised 23 reactive, 17 carcinoma and 4 suspicious for mesothelioma (confirmed on a surgical specimen). The study also used a tissue microarray of 27 epithelioid and 8 sarcomatoid mesotheliomas, and 3 benign mesothelium-lined hernia sacs.
• Exposure: No asbestos or occupational exposure was studied. The study examined staining for CAIX, alongside calretinin, Ber-EP4 and MOC31 in the fluid samples.
• Main results:
  • CAIX staining was present in 18 of 23 reactive fluids and 18 of 21 malignant fluids. Mean composite staining scores were 117 for reactive and 142 for malignant fluids. The authors reported this as no difference (P = .49).
  • In the fluid samples, CAIX stained only mesothelial cells. Inflammatory cells, macrophages and epithelial (carcinoma) cells were negative.
  • When scored as present or absent, CAIX agreed with calretinin in 89% of fluid cases. Compared case by case, CAIX composite scores were much lower than calretinin scores.
  • In the fluids suspicious for mesothelioma, CAIX staining was stronger in atypical/malignant mesothelial cells than in benign mesothelial cells.
  • In tissue, CAIX stained 26 of 27 epithelioid and 6 of 8 sarcomatoid mesotheliomas. Mean intensity was 2.68 (95% CI 2.39-2.97) for epithelioid and 1.78 (95% CI 0.81-2.74) for sarcomatoid cases. The authors reported this as no difference.
  • All three benign hernia sacs showed strong CAIX staining. In tissue, benign and malignant mesothelium stained comparably.
• The authors' conclusion: The authors concluded that CAIX can serve as an ancillary marker for mesothelial cells whether benign or malignant. Because benign mesothelial cells in fluids express CAIX, the authors stated that using it as a single marker to support a diagnosis of renal cell carcinoma in effusions could be a serious pitfall.
• Limitations the authors state:
  • Weaker CAIX staining in fluid samples may be an artifact of cell block preparation. The authors called this a limitation of the study.
  • No effusion samples with metastatic renal cell carcinoma were included.
  • The finding in sarcomatoid mesotheliomas came from a small number of cases and may need confirmation in larger series.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelium, Carcinoma, Mesothelioma, Calretinin, Ber-EP4, Epithelioid, Sarcomatoid, Mesothelial Cells.

Related studies

• Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung — M.L. Ramsey, B.J. Yuh, et al. (2012)
• Expression of carbonic anhydrase IX (CAIX) in malignant mesothelioma. An immunohistochemical and immunocytochemical study — L. Capkova, L. Koubkova, et al. (2014)
• Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma — N.G. Ordóñez (2013)
• Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia — Z. Li, L. Jiang, et al. (2019)
• The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas — M. Osborn, N. Pelling, et al. (2002)
• A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin — R.L. Attanoos, H. Goddard, et al. (1995)

Browse more research in American Journal of Clinical Pathology, or return to medical research.