Abstract： Objective To study the expression of p27 and its relationship with CpG island methylation phenotype (CIMP) in insulinoma.Methods Expression of p27 was tested in 27 insulinoma tissues and 11 paired control tissues by immunohistochemistry staining.CpG island methylation of p16,MLH1,RAR-β,MGMT,THBS1 (CIMP) was detected in 27 insulinoma tissues and 11 paired cantrol tissues by methylation specific PCR (MSP).The data of p27 and CIMP expression were correlated with the clinicopathological characteristics.Results The positive expression rate of p27 in insulinoma tissues was significantly lower than that in paired control tissues (48％ vs 91％,P =0.008).High rate of CIMP occurrence in insulinoma tissues was 33％ (9/27),while it was 18％ (2/11) in paired control tissues,and difference between the two groups was not statistically significant ( P =0.350 ).The methylation of MGMT was reversely associated with p16 methylation ( P =0.004).p27 expression in insulinoma tissues was reversely associated high rate of CIMP occurrence but it was not statistically significant ( P =0.420).Neither the expression of p27 nor the occurrence of CIMP was associated with the clinicopathological features.Conclusions Down-regulation of p27 and high rate of CIMP occurred in insulinomas,suggesting that the inactivation of p27 and epigenetic alterations of several genes might contribute to the carcinogenesis of insulinoma.