Abstract
Abstract The heparan sulfate proteoglycan Glypican-3 (GPC3) is involved in the signaling regulation of several growth factors. GPC3 is widely expressed in embryonic tissues, but disappears from most adult tissues, except for the mammary gland, among others. Several studies have involved GPC3 with cancer and some data indicate that this glypican is diminished in breast tumors. Previously, we have transfected the murine mammary tumor cell line LM3 (GPC3 negative) with the GPC3 complete cDNA sequence. We found that GPC3 reexpression is able to inhibit invasion and metastasis in vivo as well as to induce an in vitro EMT reversion, suggesting that GPC3 could act as a metastasis suppressor. The aim of the present work was to determine, in a prospective trial, whether GPC3 expression might be useful as a biomarker able to predict metastasis outcome in breast cancer patients. Our local access to a major source of breast human tissues from a representative Latin American population is an exceptional tool for the development of this new biomarker. A preliminary study was perform to analyze the expression of GPC3 at the mRNA level, by quantitative real time RT-PCR, in breast cancer samples (Brazilian n=15, Argentinean n=22) and peri-tumoral normal breast tissues (Brazilian n=16, Argentinean n=4). Even though the analyzed sample size was small, we found that both Brazilian and Argentinean tumor populations presented similar characteristics related to GPC3 expression. It was established a lower GPC3 level in tumor (n=37) than in peri-tumoral normal tissues (n=20) (p<0.001, Wilcoxon test). In matched samples, we found that 7 out of 8 tumors expressed less GPC3 than their corresponding normal peri-tumoral tissue. On the other hand, we studied by univariate analysis, the association of GPC3 expression with the parameters frequently used in the management of breast cancer patients, such as age, status, tumor size and stage, histology, metastatic axillary nodules, histological grade, nuclear grade, mitotic index, hormonal receptors, as well as with the disease-free survival probability (DFS). No association was found between GPC3 expression and these clinical-pathological parameters (Chi square and Pearson correlation tests). These results suggest the independence of GPC3 expression. The Kaplan-Meier curves and the Log Rank test indicated that GPC3 expression was not able to predict the DFS in our population of breast cancer patients. However, interestingly the only two patients who relapsed were those that expressed very low relative levels of GPC3. We believe that a longer patients’ follow-up, as well as a higher number of samples, will be needed in this prospective study to determine the usefulness of GPC3 as a biomarker to predict metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 448. doi:1538-7445.AM2012-448
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