Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses

Our plain-English summary of Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses, by T. Kawai, S. Tominaga, S. Hiroi, et al (Journal of Clinical Pathology, 2016).

The study

• Authors: T. Kawai, S. Tominaga, S. Hiroi, S. Ogata, K. Nakanishi, K. Kawahara, H. Sonobe, K. Hiroshima
• Journal: Journal of Clinical Pathology
• Published: 2016;69(8):706-12
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.

Methods: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs.

Results: Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs.

Conclusions: Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.

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In plain English

This Japanese laboratory study looked for tissue tests that help pathologists tell peritoneal malignant mesothelioma (cancer of the abdominal lining) apart from primary peritoneal serous carcinoma and reactive mesothelial hyperplasia, a non-cancerous overgrowth of the lining. The authors stained tissue from 22 mesotheliomas (18 men, 4 women), 11 serous carcinomas and 23 hyperplasia cases with 21 antibodies. They also tested some samples for loss of both copies of the 9p21 gene region (homozygous deletion). Calretinin stained 91% of mesotheliomas and none of the carcinomas. BerEP4 stained all carcinomas and no mesotheliomas. EMA stained 68% of mesotheliomas and no hyperplasia cases. Loss of both copies of 9p21 was found in 11 of 13 mesotheliomas tested and in none of 11 hyperplasia or 9 carcinoma cases. The authors suggested this high rate might reflect advanced, mostly autopsy cases. Nine patients had a history of occupational or environmental asbestos exposure. The authors concluded that calretinin and BerEP4 may be the best markers against serous carcinoma. Against hyperplasia, they found EMA with IMP3 and desmin useful, and 9p21 homozygous deletion possibly helpful.

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 diagnostic study of archived tissue: immunohistochemistry (antibody staining) and fluorescence in situ hybridisation (FISH) gene testing, comparing three diagnoses
• Who was studied: Tissue from 22 patients with peritoneal malignant mesothelioma (18 men, 4 women; mean age 61, range 23 to 90; 16 epithelioid, 6 biphasic), collected at 10 hospitals in Japan, plus 11 primary peritoneal serous carcinoma specimens and 23 reactive mesothelial hyperplasia specimens of the peritoneum
• Exposure: The study compared tissue markers rather than an exposure. Asbestos exposure history was recorded, and asbestos bodies were counted in lung tissue from some mesothelioma cases (modified Smith method), reported per gram of dry lung. Fiber types were not reported.
• Main results:
  • Calretinin was positive in 91% of peritoneal mesotheliomas (16 of 16 epithelioid, 4 of 6 biphasic) and in 0 of 11 serous carcinomas. Sensitivity was 91% and specificity 100%.
  • BerEP4 was positive in all 11 serous carcinomas and in none of the 22 mesotheliomas. Sensitivity and specificity were both 100%.
  • Claudin-4 and Pax8 were each positive in all 11 serous carcinomas and in 1 of 16 epithelioid mesotheliomas. Specificity was 95%.
  • For mesothelioma versus reactive hyperplasia, EMA was positive in 15 of 22 mesotheliomas and 0 of 23 hyperplasia cases, giving sensitivity 68% and specificity 100%.
  • For mesothelioma versus reactive hyperplasia, IMP3 had sensitivity 64% (specificity 95%) and GLUT-1 had sensitivity 50% (specificity 100%).
  • Desmin was positive in 13 of 23 reactive hyperplasia cases (57%) and in 1 of 22 mesotheliomas.
  • Homozygous deletion of 9p21 (loss of both copies) was found in 11 of 13 mesotheliomas tested and in none of 9 serous carcinomas or 11 reactive hyperplasia cases. Sensitivity was 85% and specificity 100% for mesothelioma versus hyperplasia.
  • Nine of the 22 mesothelioma patients had previous occupational or environmental asbestos exposure.
  • In lung tissue from seven mesothelioma patients, five had more than 1000 asbestos bodies per gram of dry lung, including four with more than 5000 per gram. The authors presumed these patients had occupational exposure.
  • There was no asbestos exposure in the three deciduoid-type mesothelioma cases (of five) for which information was available.
  • Of 17 diffuse mesotheliomas, 15 patients had died. The authors reported 4 of the 5 localised cases alive at 15 to 105 months.
• The authors' conclusion: The authors concluded that calretinin and BerEP4 may be the best markers for distinguishing peritoneal mesothelioma from primary peritoneal serous carcinoma. They also concluded that EMA combined with IMP3 and desmin is useful, and 9p21 homozygous deletion may be helpful, for distinguishing it from reactive mesothelial hyperplasia.
• Limitations the authors state:
  • The authors suggested their high rate of 9p21 deletion might be because their cases were all advanced and almost all were autopsy cases.
  • The authors noted that EMA's sensitivity was lower than previously reported.

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, Carcinoma, Reactive Mesothelial Hyperplasia, Peritoneum, Fluorescence In Situ Hybridization (FISH), Mesothelioma, Differential Diagnosis, Immunohistochemistry.

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