摘要目的 探讨胰岛素瘤抑癌基因p27的表达及其与CpG岛甲基化表型(CpG island methylation phenotype,CIMP)间的关系.方法 用免疫组化方法检测27例胰岛素瘤组织及11例瘤旁正常胰腺组织中p27的表达.用甲基化特异性PCR (MSP)方法检测这些组织中p16、MLH1、RAR-β、MGMT、THBS1基因的甲基化状态.分析p27表达、CIMP与临床病理参数间的相关性.结果 胰岛素瘤组织p27蛋白表达阳性率较瘤旁胰腺组织显著降低(48％比91％,P=0.008).胰岛素瘤组织的高CIMP发生率为33％(9/27),瘤旁正常胰腺组织的高CIMP发生率为18％(2/11),肿瘤组织为正常胰腺组织的2倍,但差异无统计学意义(P =0.350).胰岛素瘤的MGMT甲基化与p16的甲基化呈显著负相关(P=0.004),胰岛素瘤的p27表达与高CIMP呈负相关的趋势,但差异无统计学意义(P =0.420)；p27的表达和CIMP的发生与胰岛素瘤的临床病理参数均无显著相关性.结论 胰岛素瘤p27表达下调,并存在高CIMP,提示p27的失活和多基因的表观遗传学异常在该肿瘤的发生过程中可能起一定作用.

abstractsObjective 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.