Increased Expression of Inflammatory Markers in Type I and Type II Ovarian Carcinomas
H Arabi, S Bandyopadhyay, H Guan, K Hayek, A Munkarah, R Ali-Fehmi. Wayne State University, Detroit
Background: Recently, it has been proposed that epithelial ovarian cancers (EOC) are subdivided into 2 types: type I tumors are slow growing, genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II tumors are rapidly growing and highly aggressive neoplasms. The objective of this study was to determine the expression of inflammatory markers based on this new classification.
Design: Using our institutional database, we identified 226 cases of ovarian carcinoma treated between 1992 and 2002 for which pathological specimens were available. Patients' information and tumor characteristics were collected from the database. Survival data were retrieved from the SEER and the institutional database. Cases were categorized as Type I or Type II based on histopathology review and the above criteria. Tissue Microarray sections were stained by immunohistochemistry for Glut-1, INOS, COX-1, COX-2, and NFK-B. Expression was scored high or low based on intensity and percentage of positive cells and compared in the two types of tumors. Statistical analysis and survival data were calculated using Chi-square, T test, and Kaplan-Meier method.
Results: Table 1 compares the two groups. 89 cases were Type I, and 137 Type II. Overexpression of COX-1, COX-2, iNOS and GLUT-1 were significantly more frequent in type II tumors. In fact, there was high expression of COX-1, COX2, GLUT-1 and iNOS in 38%, 76%, 33% and 76% of type 2 tumors, an overexpression rate that is significantly higher than that seen in type I tumors(P<0.05). On the other hand, there was a trend toward lower NFK-B expression in type II tumors(p=0.053). COX-2 was an independent prognostic factor; the median survival was 28 months for tumor with high expression vs. 57 months for the low expression tumors.
* Some cases were not available for evaluation
|Type I (n=89*) (%)||Type II (n=137*) (%)||P value|
|High||8 (15)||46 (85)|
|COX-2||Low||32 (52)||30 (48)||0.01|
|High||46 (32)||96 (68)|
|Glut-1||Low||72 (46)||84 (54)||0.00|
|High||6 (12)||42 (88)|
|iNOS||Low||32 (52)||30 (48)||0.01|
|High||45 (32)||97 (68)|
|NFK-B||Low||47 (34)||91 (66)||0.05|
|High||31 (47)||35 (53)|
Conclusions: The new proposed subclassification of EOC seems to correlate with changes in the expression of various proteins of the inflammatory pathway. These changes may explain the different biologic behavior of the 2 tumor types and provide different targets for therapy based on tumor types.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 155, Wednesday Morning