Abstract 4641: IL-16 in association with VEGFR-2 detect early tumor associated changes in the ovary.
Authors: Yellapa Aparna , Bitterman Pincas , Abramowicz Jacques S. , Bahr Janice M. , Basu Sanjib , Sharma Sameer , Barua Animesh 
Published: August 2014

Abstract
Background: Ovarian cancer (OVCA) is a lethal malignancy of women with high rate of death among gynecological cancers. Due to the lack of an effective early detection test, OVCA in most cases are detected at late stage. Interleukin (IL)-16 is a cytokine involved in multiple immunopathobiological processes including inflammatory responses and production of proangiogenic cytokines. IL-16 is expressed by malignant epithelium and secreted in serum. Ovarian malignant transformation is followed by neovascularization and vascular endothelial growth factor receptor-2 (VEGFR-2) is a marker of tumor associated neovascularization (TAN). Thus, IL-16 and VEGFR-2 represent markers of OVCA at early stage may constitute an early detection test for OVCA.
Objectives: The goal of this study was to determine whether IL-16 expression is associated with ovarian malignant transformation and to examine association between serum IL-16 levels and VEGFR-2 expression by TAN vessels during ovarian tumor development.
Materials and methods: Normal (n =15) White Leghorn laying hens (3-4 years old) or hens with ovarian tumors (n=32) were selected by contrast enhanced transvaginal ultrasound scanning. Following serum collection, hens were euthanized, tissues were processed for routine histology, immunohistochemistry (IHC), protein and gene expression studies. Ovarian tumors were confirmed by gross morphology and microscopy. Expression of IL-16 by ovarian malignant epithelium and VEGFR-2 by ovarian TAN vessels were determined by IHC, immunoblotting and quantitative PCR. Serum IL-16 levels were determined by immunoassay. Correlation between serum IL-16 levels and frequencies of VEGFR-2 expressing microvessels were examined.
Results: The intensity of IL-16 expression by normal ovarian epithelium was very weak (n=15). In contrast, the staining intensity of IL-16 by malignant epithelium increased significantly (p&lt;0.001) in hens with early stage OVCA (n=15) and late stage OVCA (n=17). Compared with normal hens, serum levels of IL-16 were significantly higher in hens with early (n=15) and late stages (n=17) of OVCA (P&lt; 0.0001). The expression of IL-16 protein and mRNA were stronger in malignant ovaries than normal ovaries. The population of VEGFR-2 expressing microvessels increased significantly (p&lt;0.001) in hens with early stage OVCA than normal hens (p&lt;0.001) and increased further in late stage OVCA. The increase in serum IL-16 was positively correlated with the population of VEGFR-2 expressing TAN vessels.
Conclusion: IL-16 expression by ovarian malignant epithelium and its serum levels are associated with ovarian malignant transformation and correlated with VEGFR-2 expression. Thus IL-16 may be a useful serum marker and in combination with VEGFR-2 may detect OVCA at early stage. These findings will facilitate clinical studies to establish a non-invasive early OVCA detection test. Support: DOD Award # W81XWH-12-1-0460.
Citation Format: Aparna Yellapa, Pincas Bitterman, Jacques S. Abramowicz, Janice M. Bahr, Sanjib Basu, Sameer Sharma, Animesh Barua. IL-16 in association with VEGFR-2 detect early tumor associated changes in the ovary. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4641. doi:10.1158/1538-7445.AM2013-4641