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.

Figure 1

Box and whiskers plot of ARHI mRNA expression in 52 PETs and 16 normal pancreatic samples. Dotted line indicate the cutoff level used to distinguish samples with low (below the line) and normal (above the line) ARHI mRNA expression. WDET, well-differentiated tumor; WDEC, welldifferentiated carcinoma; PDEC, poorly differentiated carcinoma.

Figure 2

Progression free-survival curve; 49 patients with high or low ARHI mRNA expression and Ki-67 proliferation index less than or greater than 5% were considered.