Correlation of CXCR4 expression in resected pancreatic adenocarcinoma (PA) with relapse and survival after adjuvant radiochemotherapy (RCT)

Abstract

e22022 Background: The chemoreceptors CXCR4, CXCR7 and the hypoxia inductible factor-1 alpha (HIF-1α) are implicated in PA growth, dissemination and angiogenesis. These protagonists are expected to play a key role in radiotherapy and chemotherapy resistance in PA. Methods: We conducted a retrospective study of patients undergoing curative surgery (R0 resection) for PA between 2001 and 2006 in our institution. All were treated with adjuvant RCT (treatment group). The treatment group was case-matched with resected PA patients who did not receive any adjuvant therapy (control group). FFPE specimens were subjected to immunohistochemical analysis using tissue microarray and monoclonal antibodies against human CXCR4, CXCR7, and HIF-1α. Based on the intensity (I) and the extend (E) of staining, cases were stratified into those with high (E x I>3) or low (E x I ≤ 3) expression of CXCR4, CXCR7 and HIF-1α and results were correlated with disease-free survival (DFS) and overall survival (OS). Results: 31 PA patients (median age: 57years, range: 39–76) were analysed in the treatment group and 30 (median age: 59 years, range: 38–81) in the control group. The two groups were well-matched in terms of age, sex, tumor stage (T1-T2 vs T3-T4), tumor differentiation (poor vs well-moderate), lymph node (LN) status (N0 vs N+), lymphatic and vascular embols. In univariate analysis, CXCR4 expression and LN status were associated with DFS and OS (OS, CXCR4low/high: HR, 5.43, 95%CI: 2.03–14.49, p=0.001; N0/N+: HR: 4.62, 95% CI, 1.33–13.12, p=0.016; DFS: CXCR4low/ CXCR4high : HR, 3.01, 95%CI: 1.21–7.46, p=0.018; N0/N+: HR: 3.30, 95% CI, 1.09–9.90, p=0.034) in the treatment group while in the control group LN status was the only variable significantly correlated with DFS and OS. CXCR4 appeared to be the only independant predictor for DFS (CXCR4low/high: HR, 4.95, 95%CI: 1.68–14.71, p=0.007) and OS (CXCR4low/high: HR, 4.76, 95%CI: 2.03–14.49, p=0.004) in the treatment group but not in the control group. Conclusions: CXCR4 was an independant predictor for DFS and OS after adjuvant RCT in resected PA patients. This chemoreceptor could be implicated in the resistance of pancreatic cancer cells to RCT and its targeted inhibition deserves clinical evaluation. No significant financial relationships to disclose.