Integrin beta1 (ITGB1) as a prognostic marker in esophageal adenocarcinoma

Abstract

Abstract Today, individual prognosis in patients with adenocarcinoma of the esophagus (EAC) is based on post-surgical TNM staging and valid biomarkers are still not implemented. Integrin beta1 (ITGB1) is widely expressed in epithelial cells and promotes cell adhesion and growth. Its impact on tumor progression was described for different tumor entities before, data on its function as a potential biomarker in EAC is not available. Aim of the study is to evaluate the expression level of ITGB1 in a large collective of EAC and its impact on patients´ prognosis. 640 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGB1. The data was correlated with long term outcome, clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS). Of 640 patients to be analyzed, 127 (19.8%) showed expression of ITGB1. ITGB1 expression was associated with lymph node metastasis, expression of integrin alphaV and KRAS mutation status. Patients with high ITGB1 expression showed impaired overall survival (22.5 months (95% CI 15.3–29.7 months), vs. 34.1 months (95% CI 25.3–42.4 months), P = 0.024). This effect was particularly evident in the group of patients undergoing primary surgery without prior neoadjuvant therapy (10.2 months (95% CI 1.9–41.7 months) vs. 31.4 months (95% CI 21.1–144.2 months, P = 0.008). ITGB1 was also an independent prognostic marker in multivariable analysis (HR 1.696 (95% CI 1.084–2.653, P = 0.021) in patients that underwent primary surgery. We demonstrate for the first time the prognostic significance of ITGB1 expression in a large EAC patient population.