Association Between Clinicopathological Factors and Genomic Abnormalities Detected by FISH Analysis in Epithelioid Diffuse Malignant Pleural Mesothelioma

Our plain-English summary of Association Between Clinicopathological Factors and Genomic Abnormalities Detected by FISH Analysis in Epithelioid Diffuse Malignant Pleural Mesothelioma, by M. Takeda, T. Kasai, K. Hatakeyama, et al (International Journal of Surgical Pathology, 2017).

The study

• Authors: M. Takeda, T. Kasai, K. Hatakeyama, T. Nakai, H. Itami, T. Uchiyama, N. IIzuka, H. Maruyama, C. Ohbayashi
• Journal: International Journal of Surgical Pathology
• Published: 2017;25(8):668-673
• Read it: PubMed · Publisher

Abstract

Background: Abnormality of genes including 9p21 is known in malignant mesothelioma and we have examined the frequency of gene deletion and amplification using the fluorescence in situ hybridization (FISH) method. We formerly reported that abnormality of the genes was more common in the sarcomatoid type than epithelioid type. In this study, we compared the clinicopathological factors including nuclear grade (NG) and genomic abnormality in epithelioid malignant pleural mesothelioma (MPM).

Methods: Using paraffin-embedded tissues of 31 epithelioid MPMs, we investigated the presence of gene abnormalities in the genes 9p21, 1p36, 14q32, 22q12, 5p15, 6p, 8q24, and 7p12 by the FISH method, and compared the results with NG, clinical stage, and prognosis.

Results: In the higher NG group of epithelioid MPM, more gene amplifications [in particular 5p15 and 8q24(MYC)] were observed, and clinical stage was more advanced. Cases with the amplification of 7p12(EGFR) tended to exhibit a worse prognosis. The significant correlation between histological differentiation and clinical features such as prognosis was not confirmed.

Conclusions: NG status in epithelioid MPM may be related to gene alteration and clinical features.

In plain English

This study from Japan examined archived tumor tissue from 31 people with epithelioid malignant pleural mesothelioma (25 men, 6 women, median age 64.5 years) from a university pathology department, a city hospital and a medical center. Each tumor was graded I to III by combining scores for nuclear abnormality and the count of dividing cells. Using a laboratory method called FISH, the authors checked eight chromosome regions for lost pieces or extra copies, comparing results with stage and survival. The article does not report these patients' asbestos exposure. Three or more gene abnormalities were found in 3 of 12 grade I tumors and all 19 grade II or III tumors. Extra copies of 5p15 and 8q24 (MYC) were more frequent in higher-grade tumors. Higher-grade tumors, and those with more abnormalities, were more often advanced stage (III to IV). Nuclear grade was significantly related to survival, and cases with 7p12 (EGFR) amplification had significantly worse survival. A survival link was not confirmed for 9p21 deletion or tumor differentiation. The authors concluded that nuclear grade may be related to gene changes and clinical features.

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 pathology study of archived tumor tissue (case series) comparing nuclear grade and FISH-detected gene abnormalities with clinical stage and survival
• Who was studied: 31 cases of epithelioid malignant pleural mesothelioma (25 male, 6 female; median age 64.5 years, range 47 to 77). Cases came from the archives of the Department of Pathology at Nara Medical University, Kishiwada City Hospital and Hoshigaoka Medical Center, Japan. Dates are not given.
• Exposure: Asbestos exposure of these patients was not studied or reported; asbestos is mentioned only as background. The factors studied were nuclear grade (nuclear atypia plus mitotic count) and FISH-detected deletions of 9p21, 22q12, 1p36 and 14q32 and amplifications of 5p, 6p, 7p and 8q24.
• Main results:
  • Nuclear grade combined a nuclear atypia score and a mitotic count score; 12 cases (39%) were grade I, 11 (35%) grade II and 8 (26%) grade III.
  • Among the 31 cases, deletions were found at 9p21 (71%), 22q12 (26%), 1p36 (35%) and 14q32 (32%). Amplifications were found at 5p15 (48%), 6p11 (23%), 7p12 (39% in the text; 14/31, 45%, in Table 2) and 8q24 (39%).
  • Cases with 3 or more gene abnormalities: 3/12 (25%) in grade I and 19/19 (100%) in grade II or III (P less than .001). The higher-grade group showed more kinds of abnormalities, especially amplifications.
  • 5p15 amplification was found in 2/12 (17%) of grade I cases and 13/19 (68%) of grade II or III cases. 8q24 (MYC) amplification was found in 1/12 (8%) of grade I cases and 11/19 (58%) of grade II or III cases. The text reports both as higher in the high-grade group.
  • Stage by grade: of 12 grade I cases, 9 were stage I-II and 3 were stage III-IV; of 19 grade II or III cases, 5 were stage I-II and 14 were stage III-IV (P less than .01). Stage by abnormality count: of 22 cases with 3 or more abnormalities, 7 were stage I-II and 15 were stage III-IV; of 9 without, 7 were stage I-II and 2 were stage III-IV (P less than .05).
  • In epithelioid mesothelioma, nuclear grade was significantly related to prognosis. No survival figures are given in the text.
  • Cases with 7p12 (EGFR) amplification had significantly worse prognosis than cases without it.
  • A link with prognosis was not confirmed for the other gene abnormalities, including 9p21 deletion.
  • Histological differentiation (well, moderately or poorly differentiated) was not significantly related to prognosis or clinical stage.
• The authors' conclusion: The authors concluded that nuclear grade and 7p12 (EGFR) amplification were the prognostic factors in epithelioid malignant pleural mesothelioma in this study. They also concluded that nuclear grade may be related to gene alteration and clinical features.

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: Fluorescence In Situ Hybridization (FISH), Epithelioid, Pleural Mesothelioma, Malignant Mesothelioma, Sarcomatoid, Nuclear Grade, Prognosis, EGFR.

Related studies

• Comparison of genomic abnormality in malignant mesothelioma by the site of origin — M. Takeda, T. Kasai, et al. (2014)
• Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues — M. Takeda, T. Kasai, et al. (2012)
• A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma — Y. Enomoto, T. Kasai, et al. (2012)
• Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma — K. Kadota, K. Suzuki, et al. (2011)
• Putative Malignant Pleural Mesothelioma in situ (MPMIS) with Sequential Acquisition of Genomic Alterations on Fluorescence in situ Hybridization (FISH) Examination — S. Haefliger, S. Savice Prince, et al. (2021)
• p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer — T. Ito, M. Hamasaki, et al. (2015)

Browse more research in International Journal of Surgical Pathology, or return to medical research.