title: Low expression of ARHI is associated with shorter progression-free survival in pancreatic endocrine tumors.
abstract: Little is known about the molecular anomalies involved in the development and progression of malignancy of pancreatic endocrine tumors (PETs). A recently identified member of the Ras family, Ras homologue member I (ARHI), has been shown to be involved in breast, ovary, and thyroid carcinogenesis. Unlike other members, it acts as a tumor suppressor gene that inhibits cell growth. Here we analyzed the mRNA expression of ARHI in 52 primary PETs and 16 normal pancreata using quantitative reverse transcription-polymerase chain reaction. ARHI expression showed a statistically significant difference between either normal pancreas or well-differentiated endocrine tumors (WDET) and poorly differentiated endocrine carcinomas (PDECs) (P < .001 and P < .001, respectively). Moreover, ARHI expression among WDEC samples was more heterogeneous than in WDET, with several tumors showing level of expression analogous to that observed in PDECs. A significant correlation between lower ARHI expression and shorter survival (P = .020) was identified, and a low ARHI expression was associated to a shorter time to progression (P < .001), even considering the proliferation index Ki67 in the multivariate analysis. ARHI is involved in PET progression. Its mRNA expression seemed to be a prognostic factor for disease outcome and, in association with the proliferative index Ki67, a predictor for a rapid tumor relapse.
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University of Verona, Verona, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Dalai
authors.forename: Edoardo
authors.initials: E
authors.lastname: Missiaglia
authors.forename: Stefano
authors.initials: S
authors.lastname: Barbi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Butturini
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D006801:Humans; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020741:rho GTP-Binding Proteins / Q000235:genetics*
chemical_list: C117386:DIRAS3 protein, human; D012333:RNA, Messenger; D020741:rho GTP-Binding Proteins