Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung

Our plain-English summary of Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung, by M.L. Ramsey, B.J. Yuh, M.T. Johnson, et al (Virchows Archiv, 2012).

The study

• Authors: M.L. Ramsey, B.J. Yuh, M.T. Johnson, A.V. Yeldandi, D.L. Zynger
• Journal: Virchows Archiv
• Published: 2012;460(1):89-93
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

High immunohistochemical expression of carbonic anhydrase IX (CAIX) is found in clear cell renal cell carcinoma (ccRCC), but no studies have assessed CAIX in metastatic ccRCC (mccRCC) of the lung. As 75% of patients with mccRCC show lung involvement, characterization of protein expression in these lesions is warranted. This investigation analyzed CAIX immunohistochemical expression in pulmonary/pleural tumors including mccRCC (n = 22), mesothelioma (n = 19), squamous cell carcinoma (n = 27), small cell carcinoma (n = 9), and adenocarcinoma (n = 49), as well as other mesothelial lesions (n = 4). Membranous immunoreactivity was semiquantitatively evaluated for percent of cells stained and intensity. All cases of mccRCC (1+, 4.5%; 3+, 95.5%) and mesothelioma (2+, 10.5%; 3+, 89.5%) expressed CAIX. Most cases of lung squamous cell carcinoma (0, 11.1%; 1+, 25.9%; 2+, 22.2%; 3+, 40.7%) and small cell carcinoma were reactive (0, 11.1%; 1+, 22.2%; 2+, 33.3%; 3+, 33.3%), while CAIX was detected less frequently in pulmonary adenocarcinoma (0, 61.2%; 1+, 16.3%; 2+, 12.2%; 3+, 10.2%). In addition, CAIX was positive in adenomatoid tumor (3+, 100%) and mesothelial hyperplasia (3+, 100%). We demonstrate that CAIX is sensitive for mccRCC within the lung and a novel immunohistochemical marker for mesothelial proliferations, notably mesothelioma. Variable immunoreactivity is present among primary pulmonary epithelial tumors. Knowledge of expression overlap between these entities may prevent an incorrect interpretation of immunohistochemical results, particularly when limited tissue is available. As new carbonic anhydrase inhibitors are being evaluated, testing additional tumors for CAIX may lead to novel treatment options.

In plain English

This laboratory study looked at whether a protein called carbonic anhydrase IX (CAIX) appears in different tumors found in the lung and pleura (the lining around the lungs). The authors stained archived tissue from 130 tumors held at two US hospitals. These included 22 cases of clear cell kidney cancer that had spread to the lung, 19 pleural mesotheliomas, 27 squamous cell carcinomas, 9 small cell carcinomas and 49 adenocarcinomas of the lung. All 22 kidney cancer metastases and all 19 pleural mesotheliomas stained positive. In 17 of the 19 mesotheliomas (89.5%), more than half of the tumor cells stained, with no appreciable difference between epithelioid and biphasic types. Four other mesothelial lesions (one mesothelial hyperplasia and three adenomatoid tumors) also stained strongly. Among primary lung cancers, staining was found in 89% of squamous cell carcinomas, 89% of small cell carcinomas and 39% of adenocarcinomas. The authors concluded that CAIX staining has a high sensitivity for these kidney cancer metastases and for pleural mesothelioma, but that its overlap with primary lung tumors should be noted. The study did not examine asbestos or any other 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: Laboratory (immunohistochemistry) study of archived tumor tissue
• Who was studied: Tissue from 130 tumors: 22 clear cell kidney cancers that had spread to the lung, 19 pleural mesotheliomas, 1 pleural mesothelial hyperplasia, 3 adenomatoid tumors, 27 squamous cell, 9 small cell and 49 adenocarcinomas of the lung. Also examined were 24 samples of associated non-cancerous lung tissue. Samples came from The Ohio State University Medical Center and Northwestern Memorial Hospital (USA). Dates were not given.
• Exposure: Not applicable. The study measured a protein marker (CAIX) in tumor tissue and did not examine asbestos or any other exposure.
• Main results:
  • All 19 pleural mesotheliomas (13 biopsies, 6 resections) expressed CAIX. More than half of cells stained in 17 (89.5%), and 11% to 50% of cells stained in 2 (10.5%). Mean staining intensity was 2.8 on a 0 to 3 scale.
  • The mesotheliomas were 14 epithelioid and 5 biphasic, with no appreciable difference in staining between the subtypes.
  • All 22 clear cell kidney cancers that had spread to the lung (12 biopsies, 10 resections) stained positive. In 21 (95.5%), more than half of cells stained; in 1 (4.5%), 5% to 10% of cells stained.
  • Other mesothelial lesions stained strongly and diffusely. These were one pleural mesothelial hyperplasia and three adenomatoid tumors (two of the testicle, one of the fallopian tube), all with more than half of cells stained.
  • CAIX staining was found in 89% of lung squamous cell carcinomas (27 cases), 89% of small cell carcinomas (9 cases) and 39% of adenocarcinomas (49 cases).
  • Of the 49 lung adenocarcinomas, 61.2% were negative and 10.2% had more than half of cells stained.
  • Non-cancerous pleural mesothelium (3 samples) also stained strongly and diffusely.
• The authors' conclusion: The authors concluded that CAIX staining has a high sensitivity for clear cell kidney cancer that has spread to the lung and for pleural mesothelioma. They noted that primary lung tumors also stain for it, and described CAIX as an additional novel mesothelial marker.

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: Mesothelioma, Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma, Adenomatoid Tumor, Reactive Mesothelial Hyperplasia.

Related studies

• 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 IX (CAIX) does not differentiate between benign and malignant mesothelium — V. Ananthanarayanan, M. Tretiakova, et al. (2014)
• Expression of carbonic anhydrase IX (CAIX) in malignant mesothelioma. An immunohistochemical and immunocytochemical study — L. Capkova, L. Koubkova, et al. (2014)
• 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)
• The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas — M. Osborn, N. Pelling, et al. (2002)
• Genomic profiling of the genes on chromosome 3p in sporadic clear cell renal cell carcinoma — Y. Togo, Y. Yoshikawa, et al. (2016)

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