Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas

Our plain-English summary of Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas, by N.G. Ordóñez (Modern Pathology, 2013).

The study

• Author: N.G. Ordóñez
• Journal: Modern Pathology
• Published: 2013;26(4):553-62
• Cited by: 55 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Distinguishing between peritoneal epithelioid mesotheliomas and papillary serous carcinomas involving the peritoneum can be difficult on routine histological preparations, but this differential diagnosis can be facilitated by the use of immunohistochemistry. Recent investigations have indicated that PAX8, PAX2, claudin-4, and h-caldesmon are immunohistochemical markers that can assist in distinguishing between these two malignancies; however, much of the information published on the value of these markers is either insufficient or contradictory. The purpose of this study is to resolve some of the existing controversies and to fully determine the practical value of these markers for assisting in the differential diagnosis between peritoneal mesotheliomas and serous carcinomas. In order to do so, a total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas (15 primary, 30 metastatic to the peritoneum) were investigated. PAX8 and PAX2 nuclear positivity was demonstrated in 42 (93%) and 25 (56%) of the serous carcinomas, respectively, whereas none of the mesotheliomas expressed either marker. Forty-four (98%) of the serous carcinomas exhibited claudin-4 reactivity along the cell membrane, whereas none of the mesotheliomas were positive for this marker. All of the serous carcinomas and mesotheliomas were negative for h-caldesmon. Based on these results, it is concluded that PAX8 and claudin-4 have a higher sensitivity and specificity for assisting in discriminating between peritoneal epithelioid mesotheliomas and serous carcinomas when compared with all of the other positive carcinoma markers that are, at present, recommended to be included in the immunohistochemical panels used in this differential diagnosis. Even though it is highly specific, PAX2 has little practical value in the diagnosis of peritoneal epithelioid mesotheliomas as its sensitivity is low. The h-caldesmon is not useful.

In plain English

This laboratory study tested whether four tissue stains could help tell peritoneal epithelioid mesothelioma, a cancer of the abdominal lining, apart from serous carcinoma, an ovarian cancer that can look similar under the microscope. The author stained stored tissue from the University of Texas MD Anderson Cancer Center: 40 peritoneal epithelioid mesotheliomas (25 in women, 15 in men) and 45 ovarian serous carcinomas (15 primary, 30 that had spread to the peritoneum). PAX8 stained 42 (93%) of the 45 serous carcinomas, PAX2 stained 25 (56%), and claudin-4 stained 44 (98%). None of the 40 mesotheliomas stained for any of these three markers. No tumor of either kind stained for h-caldesmon. The author concluded that claudin-4 and PAX8 should be considered two primary markers for making this distinction. In the author's view, PAX2 has little or no practical value because its sensitivity for serous carcinomas was low, and h-caldesmon has no value. The author noted it was unclear whether the low PAX2 rate reflected the tumors themselves or the particular antibody used. 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, comparing two tumor types
• Who was studied: Archived tumor samples from MD Anderson Cancer Center, Houston: 40 peritoneal malignant epithelioid mesotheliomas (25 in women, 15 in men) and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum). Dates of the cases are not given.
• Exposure: Not applicable: the study tested laboratory stains (PAX8, PAX2, claudin-4, h-caldesmon) on tumor tissue. It did not examine asbestos or any other exposure.
• Main results:
  • PAX8 stained 42 (93%) of the 45 serous carcinomas, strongly in 40 of them. This was 14 (93%) of the 15 primary and 28 (93%) of the 30 metastatic cases. All 40 mesotheliomas were PAX8 negative.
  • Of the 40 mesotheliomas, none stained for PAX8.
  • PAX2 stained 25 (56%) of the 45 serous carcinomas: 8 (53%) of the 15 primary and 17 (57%) of the 30 metastatic cases. None of the mesotheliomas stained for PAX2.
  • Claudin-4 stained 44 (98%) of the 45 serous carcinomas, strongly and diffusely in 40. None of the mesotheliomas stained for claudin-4.
  • All mesotheliomas and all serous carcinomas were negative for h-caldesmon.
  • The author compared these results with figures from earlier published studies of other carcinoma markers (MOC-31, Ber-EP4, TAG-72, CD15, CA19-9), which were not tested here. On that comparison, the author judged claudin-4 to have generally higher sensitivity and specificity.
• The authors' conclusion: The author concluded that claudin-4 and PAX8 should be considered two primary markers for distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas involving the peritoneum. The author judged that PAX2 has little or no practical value because of its low sensitivity, and that h-caldesmon has no value. The author suggested that claudin-4 and PAX8 (or estrogen receptor), combined with thrombomodulin and calretinin, will usually allow the distinction.
• Limitations the authors state:
  • The same PAX2 antibody was used in this and all published studies. The author stated it is unclear whether PAX2's low sensitivity reflects true low expression in serous carcinomas or low sensitivity of this antibody.
  • The author stated that the cause of the disagreement between these h-caldesmon results and an earlier study that found h-caldesmon in mesotheliomas is unclear. The only difference noted was the antibody dilution.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

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

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)
• Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum — R.L. Attanoos, R. Webb, et al. (2002)
• Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma — Y. Ohta, Y. Sasaki, et al. (2013)
• Is PAX2 a reliable marker in differentiating diffuse malignant mesotheliomas of peritoneum from serous carcinomas of müllerian origin? — F.F. Gao, A.M. Krasinskas, et al. (2012)
• PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma — A.R. Laury, J.L. Hornick, et al. (2010)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)

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