Abstract 3190: Interleukin (IL-16) and tumor associated neo-angiogenesis detects ovarian cancer at early stage
Authors: Yellapa Aparna , Abramowicz Jacques S. , Bitterman Pincas , Bahr Janice M. , Bradaric Michael J. , Edassery Seby L. , Sharma Sameer , Barua Animesh 
Published: June 2012

Background: The lack of an early detection test is one of the reasons of high mortality rate of women due to epithelial ovarian cancer (OVCA). Understanding the pathogenesis and progression of OVCA is essential to establish an effective early detection test. Tumor associated -immuno-chemotaxis (TAI) and -neoangiogenesis (TAN) are the two earlier events in tumor development. CD8+ T cells in tumor vicinity produce immune-chemotactic IL-16 cytokines which stimulates the production of pro-angiogenic cytokines responsible for TAN. Ovarian TAI and TAN represent potential target for an effective early detection test. Access to patients at early stage OVCA is very difficult and laying hens develop spontaneous OVCA with histopathology similar to humans.

Objectives: The goal of the present study was to determine the feasibility of markers of ovarian TAI and TAN in detecting early stage OVCA in laying hens.

Materials and Methods: 3 years old laying hens (normal, low or stopped egg-laying) were scanned by Ultrasound, sera were collected, hens were euthanized and ovarian tissues were processed for paraffin and frozen sections, and mRNA extraction. Ovarian tumor stages were confirmed at gross and routine histology. Samples were divided into 4 groups namely normal (control), early stage OVCA [microscopic or tumors limited to the ovaries], late stage OVCA, with non-tumor ovarian abnormalities (atrophied ovaries). Sera were tested for IL-16 levels by ELISA and confirmed by 2D-Western blot (WB). Ovarian expression of TAN markerS (VEGF) and, neoangiogenic microvessel density (MVD) as well as IL-16 mRNA was determined.

Results: The population of CD8+ T cells and the serum IL-16 levels were significantly higher in tumor hens (P &lt; 0.05) than normal hens. Significant increase in IL-16 levels in hens with microscopic tumor (undetectable at gross examination) suggesting that serum IL-16 may be a potential indicator of ovarian tumors at very early stage. Differences in serum IL-16 levels were not observed between hens with non-tumor ovarian pathology and normal hens suggesting that increased serum IL-16 levels in OVCA hens are tumor specific. Two immunoreactive bands (12 & 50kDa) for IL-16 were identified in the ovary while only one band (50 kDa) was detected in sera suggesting that IL-16 may be the active in tetramerized form. IL-16 protein and mRNA expression as well as the frequency of MVD were significantly higher in hens with OVCA than healthy hens. VEGF expressing microvessels were localized in the ovarian stroma preceding the tumor indicating that ovarian TAN precedes tumor progression.

Conclusion: The results of the study suggest that changes in serum levels of IL-16 are positively correlated with tumor initiation and progression. Thus serum IL-16 level together with marker of ovarian TAN may constitute a feasible test for the early detection of OVCA. Support: Prevent Cancer Foundation, Sramak Foundation and DOD (OC#093303).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3190. doi:10.1158/1538-7445.AM2011-3190