MicroRNA profiling in serous cavity specimens: Diagnostic challenges and new opportunities

Our plain-English summary of MicroRNA profiling in serous cavity specimens: Diagnostic challenges and new opportunities, by L. Nicolè, F. Cappello, R. Cappellesso, et al (Cancer Cytopathology, 2019).

The study

• Authors: L. Nicolè, F. Cappello, R. Cappellesso, C.J. VandenBussche, A. Fassina
• Journal: Cancer Cytopathology
• Published: 2019;127(8):493-500
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The cytomorphologic evaluation of serous cavity specimens can quickly determine the cause of an effusion as well as the presence or absence of a neoplastic process. Ancillary tests such as immunohistochemistry and fluorescence in situ hybridization are frequently used to help to definitively identify malignant cells, determine a site of origin, and distinguish between malignant and reactive mesothelial proliferations. In recent years, microRNAs (miRNAs) have been increasingly evaluated in cytologic specimens, including those from serous cavities. The examination of miRNA is attractive because of the stability of miRNA in such specimens and data suggesting that miRNA can provide prognostic and therapeutic information in addition to its role in diagnosis. Furthermore, miRNAs exist within extracellular exosomes, and this allows for their analysis in specimens that contain only rare malignant cells, degenerated cells, or obscuring components. This review discusses the technical aspects of specimen processing for miRNA analysis, recent studies of miRNA expression in malignant serous cavity specimens, and the potential importance of miRNA expression analysis for serous cavity specimens in the near future.

© 2019 American Cancer Society.

In plain English

This was a review article, not an original study. The authors described how microRNAs (short RNA molecules) can be extracted from serous cavity specimens: fluid from around the lungs, abdomen or heart, and pelvic washings. They summarized published microRNA studies of such specimens in lung cancer, peritoneal carcinomatosis, ovarian cancer, gastric cancer and malignant pleural mesothelioma. One reviewed mesothelioma study reported 11 microRNAs significantly upregulated in malignant pleural mesothelioma tissue (18 samples) versus controls including benign asbestos-related disease (6 samples). The authors also described their own earlier work. In one study of malignant pleural mesothelioma versus reactive effusions, a combination of miRNA-21 and miRNA-126 was the best classifier, with a sensitivity of 0.86 and a specificity of 0.87. In another, miRNA-130a was significantly overexpressed in epithelioid malignant pleural mesothelioma compared with lung adenocarcinoma. The authors concluded that serous cavity specimens are a valid alternative source of microRNA. They noted that the field is still largely unexplored, that systematic validation studies and meta-analyses are lacking, and that most microRNA research used tissue, cell lines or plasma rather than cytologic specimens.

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: Narrative review of published studies and technical methods for microRNA analysis in serous cavity specimens, including the authors' own earlier studies
• Who was studied: Published studies of serous cavity specimens (pleural effusions, ascites, pericardial effusions, pelvic washings) in malignant mesothelioma, lung cancer, ovarian cancer, gastric cancer and peritoneal carcinomatosis
• Exposure: Not an exposure study: the review concerned microRNA measurement as a diagnostic and prognostic test. No asbestos or fiber exposure was studied. One reviewed study used benign asbestos-related disease samples as a comparison group.
• Main results:
  • In the authors' earlier study comparing malignant pleural mesothelioma with reactive effusions, the best classifier for distinguishing neoplastic from nonneoplastic cytologic samples was the combination of miRNA-21 and miRNA-126: sensitivity 0.86, specificity 0.87.
  • In another earlier study by the authors, comparing epithelioid malignant pleural mesothelioma with lung adenocarcinoma, miRNA-130a was significantly overexpressed in mesothelioma.
  • In a reviewed study by Ak et al of fresh-frozen tissue from malignant pleural mesothelioma (n = 18) and benign asbestos-related disease (n = 6), 11 miRNAs were significantly upregulated in mesothelioma. Four of these gave an area under the curve above 0.90 for telling mesothelioma from controls.
  • In a reviewed study by Andersen et al, which screened 742 miRNAs in surgical specimens of malignant mesothelioma and nonneoplastic pleura, 14 miRNAs differed significantly between the two groups.
  • In a reviewed study by Lin et al of pleural effusion exosomes from patients with pneumonia (n = 9), pulmonary tuberculosis (n = 9) or lung cancer (n = 9), miRNA-205-5p and miRNA-200b were markedly increased only in lung cancer.
  • In a reviewed study by Schindler et al, miRNA-21 and miRNA-186 were significantly upregulated in ascites from patients with peritoneal carcinomatosis compared with patients with spontaneous bacterial peritonitis or portal hypertension.
• The authors' conclusion: The authors concluded that serous cavity specimens are a valid alternative source of microRNA. They added that microRNA profiles in such specimens could potentially help with diagnosis, prognosis and predicting response to treatment.
• Limitations the authors state:
  • Research on microRNA in serous cavity specimens is still a largely unexplored field.
  • Systematic validation studies and meta-analyses of microRNA profiling in effusions are lacking.
  • Most cancer-related microRNA studies used tissue, cell lines or plasma rather than cytologic specimens.
  • Plasma analysis may be preferable to effusion analysis. Not all cancer patients develop effusions, blood draws are less invasive, and blood samples give more reproducible results.

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Serous Cavities.

Related studies

• Young investigator challenge: MicroRNA-21/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology — R. Cappellesso, L. Nicolè, et al. (2016)
• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)
• MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions — B. Davidson, H.T. Stavnes, et al. (2016)
• Cytomorphologic features of metastatic urothelial carcinoma in serous effusions — C.C. Huang, A. Attele, et al. (2013)
• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• Utility of HBME-1 immunostaining in serous effusions — V. Ascoli, C. Carnovale-Scalzo, et al. (1997)

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