Cell Signaling Pathways from Pancreatic Intraepithelial Neoplasia (Pan-IN) to Invasive Adenocarcinoma
Maria Teresa Salcedo, Helena Allende, Teresa Macarulla, Angeles Montero, Vicente Peg, Irene Sansano, Joaquim Balsells, Santiago Ramon y Cajal. Vall d' Hebron University Hospital, Barcelona, Spain
Background: Pancreatic adenocarcinoma (PDAC) still has a dismal prognosis. Multiple genetic alterations in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes. Furthermore, the identification of non-invasive precursor lesions (PanIN) has led to the formulation of a multi-step progression model of pancreatic cancer and the identification of early and late genetic alterations. The aims of this study were to describe the expression of factors implicated in growth and proliferation cell signaling pathways, in order to analyze the role of these factors in pancreatic malignant transformation.
Design: We study the expression of pmTor, 4E-BP1, p4E-BP1, eIF4E, peIF4E, pS6 and pMAPK in 64 specimens from pancreatectomy, with PDCA and lesions of PanIN of all histological grades, adjacent to PDCA. Levels of expression were semiquantitatively evaluated as percentage and intensity of stained tumor cells (H-score). Statistical evaluation used was Kruskal-Wallis tests.
Results: The expression of cell signaling factors implicated in mTor pathway increase with development of invasive adenocarcinoma, from low grade Pan-IN to DPCA (4E-BP1, p< 0'001; p eIF4E, p<0'001; pmTor, p<0'001; pS6, p: 0'013). pMAPK is expressed in Pan-IN 3 and DPCA, with higher levels in the invasive carcinoma areas (p:0'002)
Conclusions: In this study, we show that mTor pathway is activated in pancreatic malignant transformation since early stages, and that pMAPK is highly activated, mainly in advanced stages. With these results, we propose that: 1) the expression of factors such as pmTor, p4E-BP1 and pMAPK may provide a reliable way to identify high risk PanINs and the subsequent development of infiltrating carcinoma, 2) pmTor and pMAPK can be potential therapeutic targets in PDCA.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 165, Tuesday Afternoon