Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival

Our plain-English summary of Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival, by K. Brenne, D.A. Nymoen, T.E. Hetland, et al (Human Pathology, 2012).

The study

• Authors: K. Brenne, D.A. Nymoen, T.E. Hetland, C.G. Trope', B. Davidson
• Journal: Human Pathology
• Published: 2012;43(4):496-505
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The EHF (Ets homologous factor) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the mRNA level in a larger series. We analyzed the diagnostic role of EHF in 98 ovarian serous carcinoma effusions, 23 malignant mesothelioma specimens (20 effusions, 3 surgical specimens), and 28 primary ovarian serous carcinomas using quantitative real-time polymerase chain reaction. Expression levels of EHF in ovarian carcinoma were additionally investigated for association with clinicopathologic parameters and survival. Quantitative real-time polymerase chain reaction analysis showed significantly higher expression of EHF mRNA in ovarian carcinoma effusions and in primary ovarian carcinoma compared to malignant mesothelioma effusions (P < .001 for both). EHF mRNA expression was additionally higher in primary ovarian carcinomas compared to effusions of this cancer (P < .001). In univariate analysis for all patients with effusions, higher EHF mRNA levels were associated with a trend for shorter progression-free survival (P = .066), which became significant in analysis of 45 patients with primary diagnosis pre-chemotherapy effusions (P = .01). In Cox multivariate analysis, EHF mRNA expression was an independent predictor of poor progression-free survival for all patients and patients with primary diagnosis pre-chemotherapy effusions (P = .033 and P = .009, respectively). EHF mRNA levels differentiate ovarian carcinoma from malignant mesothelioma and may thus be of diagnostic value in this setting. EHF may be a novel prognostic marker in ovarian carcinoma.

Copyright © 2012 Elsevier Inc. All rights reserved.

In plain English

This laboratory study from the Norwegian Radium Hospital in Oslo measured EHF mRNA, a gene product, in specimens that were more than half tumor cells. The authors asked whether it could distinguish ovarian cancer from malignant mesothelioma and whether it was linked to ovarian cancer survival. They tested fluid samples (effusions) collected from 1998 to 2005: 98 from 93 women with ovarian, primary peritoneal or fallopian tube carcinoma (grouped as ovarian carcinoma) and 20 from mesothelioma patients. They also tested 28 solid ovarian serous tumors and 3 surgical mesothelioma specimens. EHF copy numbers were higher in ovarian cancer effusions (median 449, range 3 to 4881) than in the 18 successfully tested mesothelioma effusions (median 1, range 0 to 5), and higher still in solid ovarian tumors. In 45 women sampled before chemotherapy at diagnosis, mean progression-free survival was 3 months with high EHF versus 12 months with low EHF. EHF was not related to overall survival. The authors concluded EHF may help diagnosis and may be a prognostic marker. They noted short follow-up and missing data. The article does not study asbestos exposure.

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 stored tumor specimens (quantitative real-time PCR), with retrospective survival analysis of the ovarian cancer patients
• Who was studied: Specimens from the Norwegian Radium Hospital, Oslo. Effusions were collected from 1998 to 2005: 98 effusions (74 peritoneal, 24 pleural) came from 93 patients with FIGO stage II-IV ovarian carcinoma (n = 77), primary peritoneal carcinoma (n = 11) or fallopian tube carcinoma (n = 5), and 20 effusions (15 pleural, 5 peritoneal) came from malignant mesothelioma patients. The study also included 28 solid primary ovarian serous carcinomas and 3 surgical specimens of diffuse peritoneal mesothelioma. Tumor cells made up more than 50% of every specimen.
• Exposure: No asbestos or other environmental exposure was studied. The factor measured was the level of EHF (Ets homologous factor) mRNA in tumor specimens in which tumor cells made up more than 50% of the cells. Levels were normalized against the reference gene GUS.
• Main results:
  • EHF copy numbers in ovarian carcinoma effusions (n = 98) ranged from 3 to 4881 (median 449). In malignant mesothelioma effusions (n = 18 tested; 2 tests failed) they ranged from 0 to 5 (median 1). The difference was statistically significant (P less than .001).
  • Solid primary ovarian carcinomas (n = 28) had still higher EHF levels: range 74 to 21,949, median 1535. This was significantly higher than in ovarian carcinoma effusions (P less than .001).
  • The three surgical specimens of peritoneal mesothelioma had EHF levels similar to the mesothelioma effusions (copy numbers 1 to 5).
  • In ovarian carcinoma effusions, EHF levels were not related to effusion site, age, grade, FIGO stage, residual disease volume, previous chemotherapy or chemotherapy response.
  • In all 93 ovarian carcinoma effusion patients, higher EHF showed a trend toward shorter progression-free survival that was not statistically significant (P = .066). It had no relationship to overall survival.
  • In multivariate analysis of all 93 ovarian carcinoma effusion patients, EHF level (P = .033) and chemotherapy response at diagnosis (P less than .001) were independent predictors of progression-free survival.
  • Among 45 patients with pre-chemotherapy effusions at primary diagnosis, mean progression-free survival was 3 months for those with high (above median) EHF (n = 22). It was 12 months for those with low EHF (n = 23), P = .01.
  • In multivariate analysis of the 45 pre-chemotherapy patients, three factors were independent predictors of progression-free survival: EHF level (P = .009), chemotherapy response at diagnosis and residual disease volume.
  • EHF level was not related to survival in post-chemotherapy effusions.
• The authors' conclusion: The authors concluded that EHF levels were higher in ovarian carcinoma effusions than in mesothelioma effusions, and that this supports using the EHF mRNA assay as a new diagnostic test in this setting. They also concluded that EHF may be a new prognostic marker in ovarian carcinoma.
• Limitations the authors state:
  • Follow-up was short because most patients had advanced disease and did not survive long. The authors said a separate cohort with longer follow-up may be needed for definite conclusions.
  • Residual disease data were missing for some patients.
  • The diagnostic use of the assay still needs to be validated in independent series.

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: Carcinoma, Malignant Mesothelioma, Ovarian Serous Carcinoma, Progression-Free Survival, Chemotherapy, Multivariate Analysis.

Related studies

• Hepatocyte nuclear factor-1β is not a specific marker of clear cell carcinoma in serous effusions — B. Davidson (2014)
• Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma — K. Brusegard, H.T. Stavnes, et al. (2012)
• Is PAX2 a reliable marker in differentiating diffuse malignant mesotheliomas of peritoneum from serous carcinomas of müllerian origin? — F.F. Gao, A.M. Krasinskas, et al. (2012)
• Expression of thyroid transcription factor-1 in malignant pleural effusions — A. Khoor, A.L. Byrd-Gloster, et al. (2011)
• Soluble AXL is ubiquitously present in malignant serous effusions — K. Flem Karlsen, E. McFadden, et al. (2019)
• Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression — N. Nilforoushan, N.A. Moatamed (2020)

Browse more research in Human Pathology, or return to medical research.