Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues

Our plain-English summary of Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues, by M. Takeda, T. Kasai, Y. Enomoto, et al (Journal of Clinical Pathology, 2012).

The study

• Authors: M. Takeda, T. Kasai, Y. Enomoto, M. Takano, K. Morita, E. Kadota, N. Iizuka, H. Maruyama, A. Nonomura
• Journal: Journal of Clinical Pathology
• Published: 2012;65(1):77-82
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes were losses in 9p21, 1p36, 14q32 and 22q12, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. Although the diagnostic utility of 9p21 homozygous deletion by fluorescence in situ hybridisation (FISH) analysis in MM has been reported recently, alterations of other genes have not been examined to any great extent. This study analysed the frequency of various genomic gains and losses in MM using FISH analysis.

Materials And Methods: The authors performed a FISH analysis using paraffin-embedded tissues from 42 cases of MM.

Results: Chromosomal losses in MM were found at 9p21 (83%), 1p36 (43%), 14q32 (43%) and 22q12 (38%), whereas gains were found at 5p15 (48%), 7p12 (38%) and 8q24 (45%). There were no cases of adenomatoid tumour, benign mesothelial multicystic tumour, reactive mesothelial hyperplasia or pleuritis showing any gains or losses. At least one genomic abnormality was identified in all cases of MM. Among various histological subtypes, the chromosomal abnormality tended to be more common in cases showing sarcomatous elements (biphasic or pure sarcomatoid) than in cases showing an epithelioid histology.

Conclusions: The authors found various genomic gains and losses in MM by FISH analysis. The frequency of each genomic gain or loss examined in MM by FISH analysis almost agreed with the comparative genomic hybridisation technique in previous studies. This study suggests that genomic evaluation by FISH analysis might be helpful in distinguishing MM from benign mesothelial proliferation.

In plain English

This laboratory study used a technique called FISH on archived tissue samples to look for gained or lost chromosome regions in 42 malignant mesotheliomas (35 pleural, five peritoneal, two pericardial) from three Japanese institutions. For comparison, the authors tested 15 non-cancerous samples: 10 benign mesothelial lesions and five cases of pleuritis. The article did not report the patients' asbestos exposure. Among the mesotheliomas, losses were found at 9p21 in 83%, at 1p36 and 14q32 in 43% each, and at 22q12 in 38%. Gains were found at 5p15 in 48%, at 8q24 in 45% and at 7p12 in 38%. Every mesothelioma showed at least one abnormality, and none of the 15 non-cancerous samples showed any. Loss at 14q32 and gain at 8q24 were more common in biphasic or sarcomatoid tumours than in epithelioid tumours (67% vs 33% and 75% vs 33%, p less than 0.05). The changes were not associated with disease stage. The authors concluded that FISH testing of these genes might help distinguish mesothelioma from reactive mesothelial proliferation, and called for larger studies.

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 study of archived tumour tissue: FISH testing of mesothelioma samples compared with benign mesothelial lesions and pleuritis
• Who was studied: 42 malignant mesotheliomas (35 pleural, 5 peritoneal, 2 pericardial; 32 men, 10 women; median age 64, range 47 to 88), plus 10 benign mesothelial lesions and 5 pleuritis cases, from archives of Nara Medical University, Kishiwada City Hospital and Hoshigaoka Koseinenkin Hospital, Japan. Histology of the mesotheliomas: 30 epithelioid, 7 biphasic, 5 sarcomatoid.
• Exposure: Not studied. The article reports no asbestos or other exposure information for the cases. It examined genetic changes in tumour tissue.
• Main results:
  • In the 42 mesotheliomas, losses were found at 9p21 (83%, 35/42), 1p36 (43%), 14q32 (43%) and 22q12 (38%).
  • In the 42 mesotheliomas, gains were found at 5p15 (48%), 7p12 (38%) and 8q24 (45%). A gain at 6p11 was found in 9/42 (21%).
  • None of the 15 non-cancerous samples (adenomatoid tumour, benign multicystic tumour, reactive mesothelial hyperplasia, pleuritis) showed any gain or loss.
  • All 42 mesotheliomas had at least one abnormality. Counting abnormalities with all eight probes together gave 42/42 mesotheliomas versus 0/15 benign lesions (p less than 0.001).
  • Compared with epithelioid tumours, biphasic or sarcomatoid tumours more often had 14q32 loss (67% vs 33%) and 8q24 gain (75% vs 33%), both p less than 0.05. Differences for the other regions were reported as not significant.
  • Chromosomal instability, defined as abnormality in four or more of the eight regions, was more common in biphasic/sarcomatoid tumours (9/12, 75%) than in epithelioid tumours (9/30, 30%), p less than 0.01 according to Table 5.
  • Abnormal FISH patterns were not associated with stage of disease.
• The authors' conclusion: The authors concluded that examining these genes by FISH might be helpful to differentiate malignant mesothelioma from reactive mesothelial proliferation, especially in ambiguous cases.
• Limitations the authors state:
  • Other gene alterations, such as hypermethylation and point mutations, can occur at these locations and cannot be detected by FISH.
  • Larger studies of mesothelioma patients are needed to evaluate whether this diagnostic approach is valid and efficient.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Fluorescence In Situ Hybridization (FISH), Homozygous Deletion, Adenomatoid Tumor, Reactive Mesothelial Hyperplasia, Histological Subtype, Biphasic Mesothelioma, Sarcomatoid.

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