9p21 deletion in the diagnosis of malignant mesothelioma, using fluorescence in situ hybridization analysis

Our plain-English summary of 9p21 deletion in the diagnosis of malignant mesothelioma, using fluorescence in situ hybridization analysis, by M. Takeda, T. Kasai, Y. Enomoto, et al (Pathology International, 2010).

The study

• Authors: M. Takeda, T. Kasai, Y. Enomoto, M. Takano, K. Morita, E. Kadota, A. Nonomura
• Journal: Pathology International
• Published: 2010;60(5):395-9
• Cited by: 59 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as one of the most common genetic alterations in malignant mesotheliomas (MMs). Previous studies showed that this alteration might be useful for differentiating benign from malignant mesothelial tumors in cytology and surgical specimens. Although the diagnostic utility of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH) analysis has been reported only recently, it has not been well demonstrated. The purpose of this study is to evaluate the diagnostic utility of 9p21 homozygous deletion assessed by FISH in mesothelial neoplasm and hyperplasia of Japanese patients using paraffin-embedded tissue. Simultaneously, p16 protein immunoexpression was explored as a potential diagnostic aid. FISH analysis demonstrated 9p21 deletion in 35 of 40 cases with MM (88%) (P < 0.001). In contrast, no cases of adenomatoid tumor, benign mesothelial multicystic tumor, reactive mesothelial hyperplasia or pleuritis showed 9p21 deletion (P < 0.005). 9p21 homozygous deletion correlated well with p16 protein expression in the tumor cells. Our study suggests that 9p21 homozygous deletion assessed by FISH on paraffin-embedded tissue may be very useful for differentiating MM from reactive mesothelial proliferation.

In plain English

This Japanese laboratory study tested whether a genetic change, loss of both copies of a chromosome region called 9p21 (which contains the p16 gene), can help pathologists tell malignant mesothelioma apart from harmless (benign or reactive) changes in the lining tissue. The authors used archived tissue from two institutions: 40 malignant mesotheliomas (37 pleural, 1 peritoneal, 2 pericardial), 12 benign mesothelial lesions and 13 cases of pleuritis. They used a fluorescent DNA test (FISH) and two antibody stains for the p16 protein. The FISH test found the deletion in 35 of the 40 mesotheliomas (88%) and in none of the benign lesions or pleuritis cases. Neither p16 antibody stain separated the groups as well as FISH. The study did not look at asbestos exposure. The authors concluded that the FISH test could be a useful marker for telling mesothelioma from benign mesothelial proliferation, especially in ambiguous cases. They said larger studies are needed, and that FISH cannot detect some other changes at this gene region.

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 paraffin-embedded tissue, comparing a FISH test for 9p21 deletion with p16 antibody staining (immunohistochemistry) in malignant versus benign mesothelial lesions
• Who was studied: Archived tissue from 40 malignant mesotheliomas (37 pleural, 1 peritoneal, 2 pericardial; 28 epithelioid, 7 biphasic, 3 sarcomatoid, 2 desmoplastic), 12 benign mesothelial lesions (4 adenomatoid tumors of the uterus, 3 benign multicystic mesotheliomas of the peritoneum, 5 mesothelial hyperplasias) and 13 pleuritis cases. The tissue came from the archives of the Department of Pathology, Nara Medical University, and Kishiwada City Hospital, Japan. Dates are not given.
• Exposure: Asbestos exposure was not assessed. The study examined a genetic change (homozygous 9p21/p16 deletion) and p16 protein staining in tumor and benign tissue.
• Main results:
  • Malignant mesotheliomas: the FISH test found homozygous 9p21 deletion in 35 of 40 cases (88%).
  • Malignant mesotheliomas: loss of only one copy (hemizygous loss) was not found in any case.
  • No 9p21 deletion was found in adenomatoid tumor, benign multicystic mesothelioma, reactive mesothelial hyperplasia or pleuritis (P < 0.001 in the article text).
  • p16 protein staining with antibody clone 6H12 was seen in 87% of benign and 15% of malignant mesothelial lesions (P < 0.001).
  • p16 protein staining with antibody clone G175-405 was seen in 90% of benign and 33% of malignant mesothelial lesions (P < 0.001).
  • Of the 35 mesotheliomas with 9p21 deletion, one stained positive for p16 with clone 6H12 and seven with clone G175.
  • For mesothelioma versus benign mesothelial proliferations, the FISH test had sensitivity 0.88, specificity 1 and Youden index 0.88.
  • The authors judged FISH a more powerful test than either p16 antibody stain for distinguishing mesothelioma from benign lesions, based on the Youden index.
  • By mesothelioma subtype, deletion was found in 24 of 28 (86%) epithelioid, 6 of 7 (86%) biphasic, 3 of 3 (100%) sarcomatoid and 2 of 2 (100%) desmoplastic cases.
• The authors' conclusion: The authors concluded that FISH assessment of homozygous 9p21 deletion could be a useful diagnostic marker for distinguishing malignant mesothelioma from benign mesothelial proliferation, especially in ambiguous cases.
• Limitations the authors state:
  • The authors said larger series of mesothelioma patients are needed to evaluate the validity and efficiency of this approach.
  • The authors noted that some disagreements between FISH and staining results could be false-positive FISH results caused by suboptimal hybridization.
  • The authors noted that other changes at the 9p21 region, such as hypermethylation and point mutation, cannot be detected by FISH.

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: Malignant Mesothelioma, Fluorescence In Situ Hybridization (FISH), Homozygous Deletion, Cytology, Neoplasm, Adenomatoid Tumor, Reactive Mesothelial Hyperplasia.

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