Mutational analyses of multiple oncogenic pathways in intraductal papillary mucinous neoplasms of the pancreas.

摘要: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are divided into 3 groups based on increasing nuclear and architectural atypia: intraductal adenoma, borderline, carcinoma (IPMC).1 According to absence or presence neoplastic cells invading pancreatic tissue surrounding involved ducts, IPMCs separated invasive noninvasive types.2 Most IPMNs slow growing less aggressive compared with conventional, ductal adenocarcinoma (PDA). The prognosis patients IPMN consisting in situ, minimally is excellent, 5-year survival rate was reported be 77% 100%.3–6 However, that macroscopically involves parenchyma comprises 16% 43% all lesions, for these lesions varied widely from 0% 64% several series.3–5,7–9 Reported genetic alterations identified include mutations KRAS,10 TP53,11 STK11/LKB1,12 PIK3CA13 genes, as well loss heterozygosity chromosomal loci.12,14 Overexpression ERBB2 (HER2) has been reported, beginning early stage hyperplasia.15 ERBB family 4 structurally related receptors: ERBB1 (EGFR), (HER2/neu), ERBB3, ERBB4. EGFR kinase domain lung adenocarcinomas could predict significant clinical responses orally active epidermal growth factor receptor (EGFR) tyrosine inhibitors.16–18 Furthermore, 1.6% 9.8% also harbored mutations.19,20 There much accumulated evidence its members strongly implicated development progression numerous human tumors, including IPMNs, intraepithelial neoplasias, PDA.6,15 Downstream EGFR/ERBB2 signaling pathways, KRAS, BRAF, PIK3CA frequently mutated cancers act oncogenic proteins.16,21,22 Previously, we have IPMN/IPMC.13,23 Here, analyzed genes same cohort correlated their mutation status other changes.