Molecular typing of epithelial ovarian carcinomas using inflammatory markers.
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.
Ali-Fehmi
Rouba
R
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. rali@med.wayne.edu
Semaan
Assaad
A
Sethi
Sima
S
Arabi
Haitham
H
Bandyopadhyay
Sudeshna
S
Hussein
Yaser R
YR
Diamond
Michael P
MP
Saed
Ghasan
G
Morris
Robert T
RT
Munkarah
Adnan R
AR
D014408:Biomarkers, Tumor / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000032:analysis; D005260:Female; D051272:Glucose Transporter Type 1 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000401:mortality; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000401:mortality
D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D016328:NF-kappa B; C495677:SLC2A1 protein, human; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2