Abstract 3812: Retrospective analysis of Claudin-16 (CLDN16) overexpression in ovarian cancer (OVCA): Evaluation of a biomarker candidate and a novel potential therapeutic target
Authors: Paes Marcela F. , Cerri Murilo F. , Daltoé Renata D. , Dias Lucas CR , Herlinger Alice L. , Madeira Klesia P. , Silva Débora , Bacchi Carlos E. , Duarte Ivison X. , Morin Patrice J. , Silva Ian V. , Rangel Leticia B. 
Published: June 2012

Abstract
Our group has previously documented the overexpression of CLDN16 in OVCA; nonetheless the role of the phenomenon in cancer development and progression remains enlightened, even thought it points to cell permeability modification and tumor increased invasion potential. The present study aims to establish the clinical relevance of CLDN16 overexpression in OVCA, as well as to elucidate its role in ovarian carcinogenesis in order to future develop OVCA CLDN16-based diagnosis and/or therapeutic strategies. We had generated an OVCA database including patients clinical follow up. CLDN16 expression in tissue array platforms has been accessed by immunohistochemistry. The studied population profile corroborates to the worldwide OVCA statistics, with a prevalence of serous adenocarcinoma (serous: 42.5%, endometrioid: 17%, mucinous: 16%, clear cell: 11.3%), in menopausal women (mean age at diagnosis, 55.9 years), at advanced staged (FIGO stage I: 7.5%, II: 8.5%, III: 41.5%, VI: 27.4%; poor differentiated: 37.7%, moderately differentiated : 22.7%, well differentiated: 2.8%). Surprisingly, patients median survival rate was 12%, considerably lower than that estimated by WHO (30%). Investigation of CLDN16 expression profile have revealed, so far, that 67.74% of the cases overexpress the protein in cytoplasm. It has been also observed that CLDN16 expression is an OVCA-specific feature, as previously observed by our group. Despite the cellular localization of CLDN16 in OVCA cells, it has been postulated by others that cellular trafficking of CLDNs in cancer cells might derive from post-translational events, and might be related to vesicle trafficking or cellular matrix modification. CLDN16 is overexpressed in all OVCA histological types. To this point, we have found no differential CLDN16 expression in OVCA regarding the tumor degree of diferentiation, tumor platin responsiveness, patients survival rate or stages. Altogether, our data suggest that CLDN cytoplasm overexpression in OVCA cells might be an early event in ovarian malignant transformation, therefore playing a central role in ovarian tumorigenesis. Considering that CLDN16 silencing has been associated exclusively to decreases in magnesium serum levels, which can be exogenously replaced, it is a potential novel OVCA therapeutic target. Even though we still have to confirm CLDN16 cytoplasm localization in OVCA cells, we aim to develop a therapeutic strategy against OVCA. One possibility is encapsulate CLDN16 monoclonal antibody in lipid IgG-NaPi-Iib-immunoconjugated formulations. Ultimately, we believe that CLDN16 is an interesting and novel target to fight OVCA, which is the leading cause of gynecological cancers-related deaths among women.
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 3812. doi:10.1158/1538-7445.AM2011-3812