Expression of carbonic anhydrase IX (CAIX) in malignant mesothelioma. An immunohistochemical and immunocytochemical study

Our plain-English summary of Expression of carbonic anhydrase IX (CAIX) in malignant mesothelioma. An immunohistochemical and immunocytochemical study, by L. Capkova, L. Koubkova, R. Kodet (Neoplasma, 2014).

The study

• Authors: L. Capkova, L. Koubkova, R. Kodet
• Journal: Neoplasma
• Published: 2014;61(2):161-9
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is an aggressive tumor with a poor prognosis. Carbonic anhydrase IX (CAIX) is a membranously located metalloenzyme involved in pH homeostasis with influence on regulation of cell proliferation, oncogenesis and tumor progression. Much attention has been paid recently to carboanhydrases and their inhibitors as they offer an opportunity for both developing novel anticancer drugs, as well as diagnostic and prognostic tools. This study was designed to assess the expression of CAIX in malignant pleural and peritoneal mesotheliomas, their benign counterparts, and in pleural effusions from patients with malignant mesothelioma, metastatic carcinoma or a benign disease. Tissue blocks from 51 malignant mesotheliomas of pleura (47 cases; 41 epithelioid, 2 biphasic, 4 sarcomatoid) and peritoneum (4 cases; all epithelioid), 14 cases with normal or reactive pleural tissue, and 19 cell blocks were analyzed. CAIX expression was determined using immunohistochemistry and its membranous immunoreactivity was semiquantitatively evaluated. Specimens were divided into five subgroups according to the staining pattern and intensity.Overall, 92.2% (47/51) of mesotheliomas expressed CAIX. All epithelioid mesotheliomas showed CAIX positivity, which was predominantly strong and diffuse (73.3%, 33/45). Sarcomatoid mesotheliomas and sarcomatoid areas in biphasic mesotheliomas were negative. A strong diffuse staining was observed in all cases of normal mesothelia. In pleural effusions, CAIX expression was observed in malignant cells as well as in benign mesothelial cells. In conclusion, CAIX is expressed virtually in all mesotheliomas except for sarcomatoid subtype, and in benign mesothelia. There are probably more mechanisms of CAIX overexpression than hypoxia-induced in malignant mesothelioma, with the influence of other tissue specific transcription or growth factors depending on the type of the cell lineage. CAIX immunoreactivity is not a reliable diagnostic marker for distinguishing malignant cells from benign mesothelia in pleural effusions. Nevertheless, our data support the potential use of therapeutics targeting CAIX in patients with advanced mesothelioma.

In plain English

This laboratory study from University Hospital Motol in Prague looked at whether mesothelioma tissue carries a cell-surface enzyme called carbonic anhydrase IX (CAIX). The authors stained archived samples from 1999 to 2012: 47 malignant pleural mesotheliomas, 4 malignant peritoneal mesotheliomas, 14 samples of normal or reactive (inflamed) pleural lining, and fluid samples from 19 patients with pleural effusions. Overall, 47 of 51 mesotheliomas (92.2%) showed CAIX. All 45 epithelioid tumors were positive, 33 of them (73.3%) strongly and diffusely. All 4 sarcomatoid tumors were negative. All 7 normal lining samples also stained strongly, and the difference between pleural mesothelioma and non-tumor lining was not statistically significant. In effusion fluid, CAIX appeared in 6 of 6 mesothelioma samples, 4 of 6 carcinoma samples and 6 of 7 benign samples, again without a statistically significant difference. The authors concluded that CAIX cannot reliably tell malignant from benign cells in pleural fluid. They also concluded that their data support CAIX as a possible treatment target. The article did not examine 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: Laboratory (immunohistochemical and immunocytochemical) study of archived tissue and pleural fluid samples
• Who was studied: Samples from the surgical pathology files of University Hospital Motol, Prague, Czech Republic, 1999 to 2012: 47 patients with malignant pleural mesothelioma (25 male, 22 female, mean age 61.3 years), 4 with malignant peritoneal mesothelioma, 14 biopsies of normal or reactive pleural lining, and pleural fluid cell blocks from 19 patients (6 mesothelioma, 6 metastatic carcinoma, 7 benign)
• Exposure: Not reported. The study measured CAIX staining in tissue and did not examine asbestos or any other exposure
• Main results:
  • Overall, 47 of 51 mesotheliomas (92.2%) expressed CAIX
  • All 45 epithelioid mesotheliomas (pleural and peritoneal) were positive, mostly with strong diffuse staining (33/45, 73.3%)
  • The only 4 mesotheliomas without CAIX (4/51, 7.8%) were of the sarcomatoid type. Sarcomatoid areas of biphasic tumors were also unstained
  • In mesothelioma, staining showed no link to areas of dead tissue (necrosis) or to distance from blood vessels
  • All 7 normal mesothelium samples showed strong diffuse CAIX staining
  • CAIX positivity did not differ in a statistically significant way between malignant pleural mesothelioma and non-tumorous mesothelial lining (p=0.8991)
  • In pleural fluid, CAIX was found in 6 of 6 mesothelioma effusions, 4 of 6 carcinoma effusions (66.7%) and 6 of 7 benign effusions (85.7%)
  • Malignant effusions (mesothelioma and carcinoma together) were positive in 10 of 12 (83.3%), compared with 6 of 7 benign effusions. The difference was not statistically significant (p=0.6197)
• The authors' conclusion: The authors concluded that CAIX is present in virtually all mesotheliomas except the sarcomatoid type, and also in normal and reactive mesothelial cells. Because it appears in both malignant and benign cells, they concluded it is not a reliable marker of malignancy in pleural effusions. They also stated that their data support selective CAIX inhibition as a potential treatment target in advanced mesothelioma

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: Malignant Mesothelioma, Prognosis, Oncogenesis, Peritoneal Mesothelioma, Pleural Effusion, Carcinoma, Paraffin Block, Pleura.

Related studies

• Carbonic anhydrase IX (CAIX) does not differentiate between benign and malignant mesothelium — V. Ananthanarayanan, M. Tretiakova, et al. (2014)
• 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)
• 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)
• IMP3/L523S, a novel immunocytochemical marker that distinguishes benign and malignant cells: the expression profiles of IMP3/L523S in effusion cytology — K. Ikeda, G. Tate, et al. (2010)
• Morphologic and immunocytochemical performances of effusion cell blocks prepared using 3 different methods — X. Jing, Q.K. Li, et al. (2013)

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