Survivin、P16及RB表达与原发性胆囊癌发生和发展的关系

目的:探索Survivin、P16、RB表达与原发性胆囊癌发生和发展的关系.方法:选用46例原发性胆囊癌,22例癌旁黏膜,19例胆囊良性病变组织,采用免疫组化SP法定位观察Survivin、P16、RB基因蛋白表达.结果:Survivin、P16、RB在原发性胆囊癌中表达阳性率分别为69.6%(32/46),47.8%(22/46),71.7%(33/46),与胆囊良性病变(0%,73.7%,94.7%)和癌旁黏膜(0%,95.4%,95.4%)相比有显著性差异(P<0.05或P<0.01).Survivin与P16表达呈显著的负相关(r=-0.691,P<0.01).P16与RB表达也呈显著的负相关(r= -0.6556,P<0.01).P16/RB失活组Survivin阳性率为93.8%,显著高于P16 /RB 组(x~2=9.228,P<0.01).Survivin与胆囊癌的分化程度(P= 0.003)、浸润(P=0.003)和转移(P=10-6)密切相关,P16表达缺失患者更易发生淋巴结转移和周围脏器的浸润(P=0.04或P=0.001).结论:Survivin高表达,P16、RB表达缺失在原发性胆囊癌发生中起重要的调节作用.P16/ RB通路失活,结合Survivin高表达可能是胆囊细胞癌变的重要通路之一.Survivin高表达和P16表达缺失与胆囊癌的转移和浸润可能有密切关系.

Correlations of Survivin, P16 and Retinoblastoma expression with the occurrence and progression of primary gallbladder carcinoma

AIM:To investigate the roles of Survivin,P16 and Retinoblastoma(RB)protein expression in the occurrence and progression of primary gallbladder carcinoma(PGC). METHODS:Immunohistochemistry was used to detect the expression of Survivin,P16 and RB in 46 cases of PGC tissues,22 cases of cancer- adjacent tissues and 19 cases of benign lesions. RESULTS:The positive rates of Survivin,P16 and RB expression in PGC tissues were 69.6% (32/46),47.8%(22/46)and 71.7%(33/46),re- spectively,significantly different from those in the benign(0%,73.7%,94.7%)and cancer-adja- cent(0%,95.4%,95.4%)tissues(P<0.05 or P<0.01).P16 expression was negatively correlated with Survivin and RB expression(r=-0.691,P<0.01;r=-0.6556,P<0.01).The positive rate of Survivin expression in P16/RB-deleted cases was 93.8%,significantly higher than that in P16/ RB-positive ones(x~2=9.228,P<0.01).Survivin expression was also correlated closely with the differentiation degree(P=0.003),invasion depth (P=0.003)and lymph node metastasis(P=10~(-6)), while loss expression of P16 was correlated closely with the tumor invasion depth(P=0.04) and lymph node metastasis(P=0.001). CONCLUSION:P16/RB deletion in combination with high Survivin expression might be one of the critical pathways in PGC carcinogenesis,and high expression of Survivin and loss expression of P16 are correlated closely with tumor inva- sion and metastasis.