Molecular typing of epithelial ovarian carcinomas using inflammatory markers

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

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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

Fingerprint

Molecular Typing
Carcinoma
Neoplasms
Cyclooxygenase 2
Cyclooxygenase 1
Survival
Facilitative Glucose Transport Proteins
Nitric Oxide Synthase Type II
Proteins
NF-kappa B
Kaplan-Meier Estimate
Tumor Biomarkers
Immunohistochemistry
Regression Analysis

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

Cite this

Ali-Fehmi, R., Semaan, A., Sethi, S., Arabi, H., Bandyopadhyay, S., Hussein, Y. R., ... Munkarah, A. R. (2011). Molecular typing of epithelial ovarian carcinomas using inflammatory markers. Cancer, 117(2), 301-309. https://doi.org/10.1002/cncr.25588

Molecular typing of epithelial ovarian carcinomas using inflammatory markers. / Ali-Fehmi, Rouba; Semaan, Assaad; Sethi, Sima; Arabi, Haitham; Bandyopadhyay, Sudeshna; Hussein, Yaser R.; Diamond, Michael Peter; Saed, Ghasan; Morris, Robert T.; Munkarah, Adnan R.

In: Cancer, Vol. 117, No. 2, 15.01.2011, p. 301-309.

Research output: Contribution to journalArticle

Ali-Fehmi, R, Semaan, A, Sethi, S, Arabi, H, Bandyopadhyay, S, Hussein, YR, Diamond, MP, Saed, G, Morris, RT & Munkarah, AR 2011, 'Molecular typing of epithelial ovarian carcinomas using inflammatory markers', Cancer, vol. 117, no. 2, pp. 301-309. https://doi.org/10.1002/cncr.25588
Ali-Fehmi R, Semaan A, Sethi S, Arabi H, Bandyopadhyay S, Hussein YR et al. Molecular typing of epithelial ovarian carcinomas using inflammatory markers. Cancer. 2011 Jan 15;117(2):301-309. https://doi.org/10.1002/cncr.25588
Ali-Fehmi, Rouba ; Semaan, Assaad ; Sethi, Sima ; Arabi, Haitham ; Bandyopadhyay, Sudeshna ; Hussein, Yaser R. ; Diamond, Michael Peter ; Saed, Ghasan ; Morris, Robert T. ; Munkarah, Adnan R. / Molecular typing of epithelial ovarian carcinomas using inflammatory markers. In: Cancer. 2011 ; Vol. 117, No. 2. pp. 301-309.
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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.",
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AB - 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.

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