Abstract A107: c-Met overexpression as an independent prognostic biomarker and therapeutic target in patients with poor prognostic pancreatic adenocarcinoma following surgical resection

摘要: Context: Hypoxia-induced activation of the HGF/c-Met pathway is involved in tumor-stroma interactions and invasion pancreatic ductal adenocarcinoma (PDAC). Assessment c-Met expression a critical issue as inhibitors are under clinical development PDAC. Patients methods: with resected PDAC no perioperative chemotherapy/radiotherapy were retrospectively selected to assess “pure” prognostic value molecular biomarkers. immunostaining was graded using standard visual scale combining surface (S) intensity (I) (SI) or simplified score (high c-Met: ≥20% cancer cells strong staining). Hypoxia assessed by HIF-1α CA9 immunostainings, CD31 (microvascular density), necrosis. Clinical, pathological, biomarkers correlated disease-free (DFS) overall (OS) survivals. Computer-assisted classification performed Aperio® software. who had received adjuvant treatment (chemotherapy and/or radiotherapy) for validation step on tissue microarrays (TMA). Results: Thirty-seven patients analyzed. The best reproducibility. Using this score, high (7/37) associated shorter DFS (6.3 vs 33.0 months, HR: 3.456, p=0.0036) OS (10.8 39.0 4.257, p=0.0004). In multivariate analysis, independently both (p=0.030) (p=0.004). concordant entire section TMA 87.9%, quantifiable specific computer-assisted algorithm (36/37 tumors correctly classified). There correlation between hypoxia-related markers study. cohort (n=94), significantly (9.4 18.4 1.830, p=0.0198). Conclusion: an independent marker that may help identifying at risk recurrence poor survival. robust reproducible, could be used reliable scoring method routine use larger predictive studies TMA. overexpressing represent subgroup candidate intensified trials inhibitors. Citation Format: Cindy Neuzillet, Jerome Cros, Annemilai Tijeras-Raballand, Armand De Gramont, Julien Moroch, Louis Mestier, Pierre Bedossa, Valerie Paradis, Alain Sauvanet, Jean-Baptiste Bachet, Esteban Cvitkovic, Eric Raymond, Pascal Hammel, Anne Couvelard. overexpression biomarker therapeutic target following surgical resection. [abstract]. In: Proceedings AACR Special Conference Pancreatic Cancer: Innovations Research Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A107.