PINCH-2 expression in cancers involving serosal effusions using quantitative PCR

Our plain-English summary of PINCH-2 expression in cancers involving serosal effusions using quantitative PCR, by Y. Yuan, H.P. Dong, D.A. Nymoen, et al (Cytopathology, 2011).

The study

• Authors: Y. Yuan, H.P. Dong, D.A. Nymoen, J.M. Nesland, C. Wu, B. Davidson
• Journal: Cytopathology
• Published: 2011;22(1):22-9
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: The PINCH-2 gene was previously shown to be overexpressed in malignant mesothelioma compared with ovarian/peritoneal serous carcinoma in Affymetrix array analysis. The objective of the present study was to validate this finding at the mRNA and protein level.

Methods: Effusions (n = 91; 71 ovarian and 10 breast carcinomas, 10 malignant mesotheliomas) were assayed for PINCH-2 mRNA expression using quantitative PCR. PINCH-2 protein expression was analysed in 37 effusions using flow cytometry.

Results: Quantitative PCR analysis showed significantly higher PINCH-2 mRNA levels in mesotheliomas compared with carcinomas (P = 0.004). Values of <10 copies were found exclusively in carcinoma effusions (25.4% of ovarian and 50% of breast carcinomas). However, PINCH-2 protein expression by flow cytometry did not differ significantly between the three cancer types. No association was observed between PINCH-2 levels and patient survival or expression of previously-studied molecules related to adhesion, metastasis and apoptosis inhibition in ovarian carcinoma.

Conclusions: Our data suggest that PINCH-2 mRNA is overexpressed in malignant mesothelioma compared with carcinomas involving serosal cavities, and that low levels of this gene argue against the diagnosis of mesothelioma. The frequent PINCH-2 protein expression in all three studied cancers suggests a role for this molecule in cancer cell biology in effusions and merits further research.

© 2010 Blackwell Publishing Ltd.

In plain English

This laboratory study, from a hospital in Oslo, Norway, tested whether a gene called PINCH-2 could help tell malignant mesothelioma apart from carcinomas that spread into the chest or abdominal cavities. The authors examined fluid samples (effusions) collected for diagnosis between 1998 and 2006. There were 71 from ovarian, primary peritoneal or fallopian-tube carcinoma, 10 from breast carcinoma and 10 from malignant mesothelioma (seven pleural, three peritoneal). The article does not report asbestos exposure. PINCH-2 messenger RNA was found in all 91 samples, but levels were significantly higher in mesothelioma than in the two carcinoma types (P = 0.004). Values below 10 copies occurred only in carcinoma samples. All 37 samples tested for PINCH-2 protein contained it, and the difference between cancer types was not statistically significant (P = 0.286). In the ovarian, primary peritoneal and fallopian-tube group, PINCH-2 mRNA levels were not significantly associated with survival or with the other molecules tested. The authors concluded that PINCH-2 may have diagnostic value as part of a larger gene panel, and that mesothelioma was unlikely below a low cut-off level. No high level was diagnostic for mesothelioma.

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 stored effusion specimens. It used quantitative PCR to measure mRNA and flow cytometry to measure protein, to check earlier gene array findings.
• Who was studied: Effusion specimens submitted for routine diagnosis to the Norwegian Radium Hospital, 1998 to 2006. For mRNA testing there were 91 effusions. Of these, 71 were grouped as ovarian or primary peritoneal carcinoma and came from 68 patients: 58 with ovarian carcinoma, 7 with primary peritoneal carcinoma and 3 with the closely related serous carcinoma of the fallopian tube. A further 10 were breast carcinoma (pleural) and 10 were malignant mesothelioma (7 pleural, 3 peritoneal; epithelioid or biphasic type). For protein testing there were 37 effusions: 24 ovarian or primary peritoneal carcinoma, 6 mesothelioma and 7 breast carcinoma.
• Exposure: The article does not report asbestos or other fiber exposure. The factor studied was the level of PINCH-2 mRNA and protein in cancer cells in the effusions.
• Main results:
  • PINCH-2 mRNA was detected in all 91 effusions, whatever the tumour type.
  • Median PINCH-2 copy numbers were 33.17 for the ovarian or primary peritoneal carcinoma group (range 1.17 to 453.06), 9.53 for breast carcinoma (range 1.57 to 75.52) and 97.58 for mesothelioma (range 12.45 to 1456.91).
  • PINCH-2 mRNA was significantly higher in mesothelioma than in the two carcinoma types (P = 0.004).
  • Values below 10 copies were found only in carcinoma effusions: 25.4% of the ovarian or primary peritoneal carcinoma effusions and 50% of the breast carcinoma effusions.
  • PINCH-2 protein was found in tumour cells in all 37 effusions tested by flow cytometry. The median percentage of positive cells was 15 for ovarian or primary peritoneal carcinoma, 8 for breast carcinoma and 41 for mesothelioma.
  • The higher protein expression in mesothelioma was not statistically significant (P = 0.286).
  • In the ovarian, primary peritoneal and fallopian-tube carcinoma group, PINCH-2 mRNA levels were not associated with any of the previously studied adhesion, metastasis or apoptosis-related molecules (27 to 60 specimens per analysis).
  • In the same group, PINCH-2 mRNA levels were not significantly associated with clinicopathological parameters, including overall and progression-free survival. Higher levels went with overall survival of 30 months, compared with 36 months for lower-than-median levels, but this difference was not statistically significant (P = 0.12).
• The authors' conclusion: The authors concluded that qPCR confirmed higher PINCH-2 mRNA in mesothelioma than in ovarian or primary peritoneal carcinoma and breast carcinoma effusions. They suggested a diagnostic value for this molecule as part of a larger gene panel.
• Limitations the authors state:
  • No high cut-off level was found that was diagnostic for mesothelioma. There was only a low cut-off below which mesothelioma was unlikely.
  • Protein levels overlapped between the three cancer types, so the authors judged the flow cytometry assay to have little diagnostic value for telling them apart.
  • The number of mesothelioma specimens was too small to evaluate the clinical role of PINCH-2 in mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Carcinoma, Mesothelioma, Metastasis, Apoptosis.

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• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)
• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma — E.T. Taube, C. Denkert, et al. (2017)

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