Abstract A238: c-MET as a target for MET inhibitors in patients with poor prognostic pancreatic adenocarcinoma following completed surgical resection.

摘要: Context: Pancreatic adenocarcinoma (PAC) displays a prominent desmoplastic stromal reaction, leading to tumor hypoxia and driving selective pressure that selects cells exhibiting aggressive phenotypes. Activation of the HGF/c-MET pathway is involved in tumor-stroma interactions promotes PAC proliferation, invasion, EMT, stem cellness. As background for identifying tumors could benefit from MET inhibitors, we set study looking at c-MET expression PAC. Patients Methods: Patients who underwent curative surgical resection received no adjuvant chemotherapy (“pure” prognostic value) were selected this study. was assessed using immunochemistry graded on scale 0 4, along with microenvironment characteristics as defined by HIF-1α CA9 immunostaining (hypoxia), CD31 (microvascular density [MVD]), stroma abundance. Clinical, pathological, molecular biomarkers have been correlated disease-free (DFS) overall (OS) survivals. Results: thirty-seven patients analyzed Twenty-seven percent (10/37) expressed high (score ≥ 3). High associated moderate/poor differentiation (p = 0.017), presence isolated 0.023), low abundance (r -0.445, p 0.0074), but not hypoxia-related markers (HIF-1α, CA9, or MVD). shorter DFS (median: 7.7 vs 33.0 months, HR: 2,207, p=0.025) OS 12.1 38.9 p=0.0099) than PAC. combined size lymph node ratio (defined nodes metastasis total dissected) predicted risk early local distant recurrence (RFS < 12 months) an AUC 0.836. Conclusion: appears be strong marker completely resected may help identify recurrence. Although number entered limited, suggests explore anti-metastatic potential inhibitors expressing following complete resection. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A238. Citation Format: Cindy Neuzillet, Jerome Cros, Annemilai Tijeras-Raballand, Julien Moroch, Louis de Mestier, Maryse Baia, Pierre Bedossa, Valerie Paradis, Alain Sauvanet, Jean-Baptiste Bachet, Eric Raymond, Pascal Hammel, Anne Couvelard. target poor pancreatic completed resection. [abstract]. In: Proceedings AACR-NCI-EORTC International Conference: Molecular Targets Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Suppl):Abstract nr A238.