Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Rouba Ali-Fehmi, Assaad Semaan, Sima Sethi, Haitham Arabi, Sudeshna Bandyopadhyay, Yaser R. Hussein, Michael P. Diamond, Ghasan Saed, Robert T. Morris, Adnan R. Munkarah

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Background: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. Methods: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. Results: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P <.05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P =.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P =.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P =.005). Conclusions: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy.

Original languageEnglish (US)
Pages (from-to)301-309
Number of pages9
JournalCancer
Volume117
Issue number2
DOIs
StatePublished - Jan 15 2011

Keywords

  • cyclooxygenase-1
  • cyclooxygenase-2
  • glucose transporter protein 1
  • immunohistochemistry
  • inducible nitric oxide synthase
  • nuclear factor kappa B
  • ovarian carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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