Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion

Our plain-English summary of Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion, by G.Y. Ma, S. Shi, P. Wang, et al (Biomedical Reports, 2022).

The study

• Authors: G.Y. Ma, S. Shi, P. Wang, X.G. Wang, Z.G. Zhang
• Journal: Biomedical Reports
• Published: 2022;17(2):66
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The diagnostic value of the 9P21 gene determined using fluorescence in situ hybridization (FISH) combined with BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) expression detection by immunohistochemistry, was investigated in serous effusion samples of malignant mesothelioma. A total of 70 serous disease samples with serous effusion were collected from June 2017 to June 2020. Following biopsy specimen pathological diagnosis, samples were divided into malignant mesothelioma and benign mesothelioma. Differential expression of BAP1 and MTAP genes were identified in mesothelioma and mesenchymal hyperplasia. The 9P21 gene fragment was lost in mesothelioma. The positive rates of FISH, BAP1 and MTAP in biopsy specimens were 98.00, 94.00 and 90.00%. The specificity of the three were 96.00, 85.71 and 77.27%, the sensitivity were 90.00, 95.92 and 93.75%, and the positive rate of the combined detection of the three was 93.33%. The positive rate of serous fluid samples detected by the three methods (9P21 FISH probe combined with BAP1 and MTAP expression detected immunohistochemically) was 96.00, 92.00 and 88.00%, the specificity were 90.00, 77.27 and 71.43%, the sensitivity was 96.00, 93.75 and 89.80%, and the positive rate of the three combined detections was 91.33%. It was demonstrated that there was a high consistency between serous fluid samples and biopsy samples. According to clinicopathological analysis, sex, age, lesion site, Ki67 had little association with the occurrence and development of malignant mesothelioma, while asbestos exposure history was closely associated to the occurrence of mesothelioma. A high level of BAP1 gene was positively associated with the prognosis of mesothelioma, while a high level of MTAP gene was negatively associated with the prognosis of mesothelioma (P<0.05). Therefore, 9P21 FISH probe combined with BAP1 and MTAP can be used as a new method for the detection of malignant mesothelioma, and provide an important basis for the early diagnosis of mesothelioma.

Copyright: © Ma et al.

In plain English

This study, from Cangzhou People's Hospital in China, looked back at laboratory tests for diagnosing malignant mesothelioma in fluid that collects around the lungs or abdomen (serous effusion). It included 70 patients treated from June 2017 to June 2020. The tables show 50 with malignant mesothelioma and 20 with benign tissue. In both biopsy tissue and fluid samples, the authors tested for loss of the CDKN2A gene in the 9p21 region using a FISH probe, and for the BAP1 and MTAP proteins by immunohistochemistry. The reported combined positive rate was 93.33% in biopsies and 91.33% in fluid samples, and the two kinds of sample gave closely matching results. Of the 50 mesothelioma patients, 26 had an asbestos exposure history. The authors reported an association with asbestos exposure history, but none with sex, age, lesion site or Ki67. They reported that higher MTAP was linked to worse survival. The article's statements about BAP1 and survival contradict each other. Asbestos fiber types were not reported. The authors concluded that the combined tests can be used to diagnose malignant mesothelioma in effusion samples.

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: Retrospective diagnostic test evaluation study (laboratory testing of stored biopsy and effusion specimens, with survival analysis)
• Who was studied: 70 patients with thoracic and peritoneal diseases treated at Cangzhou People's Hospital, Hebei, China, June 2017 to June 2020. According to the tables, 50 had malignant mesothelioma (epithelial type, by the inclusion criteria) and 20 had benign mesenchymal tissue. The mesothelioma cases were 17 pleural, 25 peritoneal and 8 other sites (greater omentum, ovary, appendix, etc.).
• Exposure: The study evaluated diagnostic tests: a CDKN2A (9p21) gene-deletion FISH probe, and BAP1 and MTAP immunohistochemistry, applied to biopsy and serous effusion samples. Asbestos exposure history was recorded as yes or no; questionnaires asked about the nature of the patients' work. No fiber types, products or doses were given.
• Main results:
  • In biopsy specimens, the positive rates for CDKN2A FISH, BAP1 and MTAP were 98.00, 94.00 and 90.00%. Specificity was 96.00, 85.71 and 77.27%, and sensitivity was 90.00, 95.92 and 93.75%, as printed. The combined test positive rate in biopsies was 93.33%.
  • In serous fluid samples, the positive rates for CDKN2A FISH, BAP1 and MTAP were 96.00, 90.00 and 88.00% (the abstract gives 92.00% for BAP1). Specificity was 90.00, 77.27 and 71.43%.
  • The combined three-test positive rate was 91.33% in serous fluid specimens and 93.33% in biopsy specimens. The authors described the results of the two kinds of specimen as highly consistent.
  • For each of the three tests, results in biopsy specimens and effusion specimens were associated (P less than 0.01, Table VI).
  • Among the 50 malignant mesothelioma patients, 26 had an asbestos exposure history and 24 did not. In analyses of BAP1 and MTAP expression by clinical features, the authors reported an association with asbestos exposure history: P less than 0.05 in the text and P less than 0.01 in Tables IV and V. They reported no association with sex, age, lesion site or Ki67.
  • Among mesothelioma patients, higher MTAP expression was associated with worse survival (P less than 0.05 in the text; P=0.011 in the Figure 3 legend).
  • The results text states that high BAP1 expression was associated with poor survival (P=0.044 in the Figure 3 legend). The abstract instead says high BAP1 was positively associated with prognosis.
• The authors' conclusion: The authors concluded that, in serous effusion specimens, CDKN2A FISH combined with BAP1 and MTAP immunohistochemistry can be used to diagnose malignant mesothelioma. They noted that such specimens are easier to obtain than needle biopsies and cause less trauma to patients.
• Limitations the authors state:
  • Effusion specimens contain few cells, the cells are often atypical, they were not extracted at the same time, and patients were in different positions when fluid was drawn. The authors said these factors affect diagnostic accuracy in effusion specimens.
  • Differences in immunohistochemistry conditions, such as the antibody clone or the fixation and staining procedures, may contribute to differences in results.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, MTAP, Prognosis, Mesothelioma, Fluorescence In Situ Hybridization (FISH), Immunohistochemistry, Biopsy, Serous Fluid.

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