Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma

Our plain-English summary of Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma, by K. Brusegard, H.T. Stavnes, D.A. Nymoen, et al (Virchows Archiv, 2012).

The study

• Authors: K. Brusegard, H.T. Stavnes, D.A. Nymoen, K. Flatmark, C.G. Trope, B. Davidson
• Journal: Virchows Archiv
• Published: 2012;460(2):193-202
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Rab25, an epithelial-specific member of the Rab family of small GTPases, 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 and protein level. Quantitative PCR analysis of 112 Müllerian serous carcinomas (84 effusions, 28 primary ovarian carcinomas) and 22 malignant mesotheliomas (19 effusions, 3 solid specimens) showed significantly higher RAB25 mRNA expression in the former tumor (p < 0.001). Immunohistochemical analysis of Rab25 protein expression in 245 effusions showed significantly higher expression of this protein in Müllerian serous carcinoma compared to malignant mesothelioma (189/209 vs. 12/36 positive tumors, respectively; p < 0.001). Immunostaining of 101 patient-matched solid Müllerian carcinoma specimens (34 primary carcinomas, 67 metastases) showed expression levels comparable to effusions (94/101 positive specimens; p > 0.05). Rab25 mRNA and protein expression levels in Müllerian carcinoma effusions did not correlate with overall or progression-free survival. Our data confirm that Rab25 effectively differentiates Müllerian carcinomas from malignant mesothelioma at the mRNA and protein level, suggesting a role in the diagnostic work-up of serosal cancers.

In plain English

This laboratory study, from the Norwegian Radium Hospital in Oslo, tested whether a protein called Rab25 can help pathologists tell Müllerian serous carcinoma (cancers of the ovary, fallopian tube or peritoneum) apart from malignant mesothelioma in fluid samples (effusions) from the chest or abdomen. It did not study asbestos exposure. The authors first measured the Rab25 gene's mRNA. In 84 carcinoma effusions, the count ranged from 1 to 3,204 copies (median 416). Among 19 mesothelioma effusions, 16 had no copies and 3 had one copy, and three solid mesothelioma samples had 0 to 2 copies. When samples were stained for the Rab25 protein, it appeared in 189 of 209 carcinoma effusions (90%) and in 12 of 36 mesothelioma effusions (33%). Solid ovarian tumors showed levels similar to the effusions. Among carcinoma patients, Rab25 levels were not significantly associated with overall or progression-free survival. The authors concluded that Rab25 effectively differentiates Müllerian carcinomas from mesothelioma and may be a new diagnostic marker. They noted that few mesothelioma biopsies were analyzed and that the mRNA and protein tests used different patient groups.

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 using quantitative PCR (mRNA) and immunohistochemistry (protein) on stored tumor samples, to validate an earlier microarray finding
• Who was studied: Samples from the Department of Pathology, Norwegian Radium Hospital, Oslo, 1998–2011. The mRNA analysis covered 84 Müllerian serous carcinoma effusions (64 peritoneal, 20 pleural), 19 malignant mesothelioma effusions (14 pleural, 5 peritoneal; epithelioid or biphasic type), 28 primary serous ovarian carcinomas and 3 diffuse malignant peritoneal mesothelioma specimens. The protein analysis covered 245 effusions (209 Müllerian serous carcinoma, 36 malignant mesothelioma) plus 101 solid serous ovarian carcinomas (34 primary, 67 metastases).
• Exposure: No asbestos or other environmental exposure was studied. The study measured Rab25 mRNA and protein levels in tumor samples.
• Main results:
  • Rab25 mRNA: Müllerian carcinoma effusions had 1 to 3,204 copies (median 416). Malignant mesothelioma effusions had no copies (16 specimens) or one copy (3 specimens). p less than 0.001.
  • The three solid malignant mesothelioma specimens had 0 to 2 copies of Rab25 mRNA.
  • Primary ovarian carcinomas had Rab25 mRNA levels of 22 to 3,386 (median 763). The difference from Müllerian carcinoma effusions was not statistically significant.
  • Rab25 protein was found in the cytoplasm of tumor cells in 189/209 (90%) Müllerian carcinoma effusions and in 12/36 (33%) malignant mesothelioma effusions.
  • Nuclear Rab25 staining was seen in 33/209 Müllerian carcinoma effusions and in none of the malignant mesothelioma cases.
  • In solid serous ovarian carcinomas, Rab25 protein was found in 31/34 (91%) primary tumors and in 63/67 (94%) metastases. There was no significant difference between patient-matched effusions and solid lesions.
  • In Müllerian carcinoma patients, Rab25 mRNA or protein levels showed no significant association with overall survival or progression-free survival.
  • In Müllerian carcinoma effusions, Rab25 mRNA was significantly associated with younger patient age (60 or under vs over 60).
• The authors' conclusion: The authors concluded that Rab25 effectively differentiates Müllerian carcinomas from malignant mesothelioma at the mRNA and protein levels and may be a new marker in the diagnostic panel for serosal tumors. They also concluded that their data do not support a role for Rab25 in predicting outcome in Müllerian carcinoma.
• Limitations the authors state:
  • Only a small number of malignant mesothelioma biopsies (solid specimens) were analyzed.
  • The mRNA and protein analyses were done on different patient groups. The authors also noted that mRNA levels often correlate poorly with protein levels.

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinoma, Malignant Mesothelioma, Progression-Free Survival.

Related studies

• 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 the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum — R.L. Attanoos, R. Webb, et al. (2002)
• Hepatocyte nuclear factor-1β is not a specific marker of clear cell carcinoma in serous effusions — B. Davidson (2014)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)
• Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas — N.G. Ordóñez (2013)

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