Abstract 443: Expression of the RECK tumor and metastasis suppressor gene in human breast cancer: a poor prognosis marker

Abstract

Abstract Metastasis is the main cause of mortality in breast cancer human patients. The organized breakdown of the extracellular matrix (ECM) compounds by matrix metalloproteinases (MMPs) is the key event in this metastatic process. Consistent with their role in tumor progression, high levels of several MMP family members have been shown to be correlated with poor prognosis. The MMP activities are tightly regulated by their inhibitors, namely: the metalloproteinases tissue inhibitors (TIMPs) and the membrane-associated inhibitor (RECK - Reversion-inducing Cysteine-rich protein with Kazal motifs). Due to RECK's ability to down modulate MMPs (MMP-2, 9 and 14), it is described as an important inhibitor of invasion and metastasis in several types of cancer. In order to investigate possible correlations between the RECK expression profile and clinical-pathological data in a breast cancer model, we evaluated the RECK protein in 1,040 tissue samples from invasive breast tumors using Tissue Microarray Assays (TMA). Associations between RECK expression and different clinical-pathological parameters and other biomarkers were evaluated using the Chi-square test. RECK immunoreactivity was significantly associated with higher SBR grade (p<0.05) and TNM stage (p=0.002). Moreover, higher RECK expression levels were correlated with p53 (p<0.001), her-2 (p=0.011), CK5,6 (p<0.001) and egfr (p<0.001) positivity. We also analyzed the relationship between RECK expression and the patient outcome, using Kaplan-Meier curves, demonstrating that patients with RECK positive tumors display significantly shorter disease free survival time (p=0.031) than those with RECK negative tumors. Furthermore, RECK expression was positively correlated with short disease free survival in five-years in patients diagnosed with tumors: low SBR grade (p=0.03), her-2 negative (p<0.05) and luminal markers (CK8/CK18) positive (p=0.02 and p=0.003, respectively). In addition, RECK was a predictor of poor prognosis for post-menopause (p=0.011) and patients older than 50 years (p=0.05). All together, our results indicate that higher RECK expression is associated with poor prognosis variables, being a predictor of shorter disease-free survival in five years. Moreover, we verified that RECK is a biomarker of poor prognosis mainly for patients diagnosed with less aggressive breast tumor. Therefore, in contrast to other tumor types, our results indicate that RECK is related to a more aggressive phenotype. Support: FAPESP, CNPq, FINEP, CAPES, BNDES 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 443. doi:1538-7445.AM2012-443