Low Expression of ARHI Is Associated with Shorter Progression-Free Survival in Pancreatic Endocrine Tumors

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2007-03, Vol.9 (3), p.181,IN1-183,IN2
• Main Authors: Dalai, Irene, Missiaglia, Edoardo, Barbi, Stefano, Butturini, Giovanni, Doglioni, Claudio, Falconi, Massimo, Scarpa, Aldo
• Format: Article
• Language: English
• Subjects: ARHI; Disease Progression; Genes, Tumor Suppressor; Humans; Pancreas - metabolism; pancreatic endocrine tumor; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Reverse Transcriptase Polymerase Chain Reaction; rho GTP-Binding Proteins - genetics; RNA, Messenger - analysis; survival; time to progression; tumor differentiation
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1593/neo.06838

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.