目的:探讨肾细胞癌患者肾癌组织及其相应癌旁(〉5cm)组织中胰岛素样生长因子Ⅱ(IGF-Ⅱ)基因的印迹状态,初步研究其在肾细胞癌的发生、发展中的关系.方法:根据IGF-Ⅱ基因第9外显子具有Apal位点多态性,用聚合酶链反应结合限制性片段长度多态性技术分析IGF-Ⅱ基因印迹状态.结果:30例肾细胞癌患者中癌及相应癌旁组织IGF-Ⅱ均发生杂合子基因型的有19例(63.3%),其中癌及相应癌旁组织均发生IGF-Ⅱ印迹丢失(LOI)13例(68.4%);癌组织发生IGF-ⅡLOI而其相应的癌旁组织未发生IGF-ⅡLOI为1例(5.3%);22例透明细胞性肾细胞癌中有10例(45.45%)癌及相应癌旁组织均发生LOI;5例乳头状肾细胞癌中有2例(40%)癌及相应癌旁组织均发生IGF-ⅡLOI;2例嫌色性肾细胞癌中有1例(50%)癌及相应癌旁组织均发生IGF-ⅡLOI;1例黏液样小管状和梭形细胞癌的癌组织发生了IGF-ⅡIOI而其相应的癌旁组织IGF-Ⅱ印迹正常.并且在14岁到68岁各年龄段都有IGF-ⅡLOI的发生,且发生频率接近,表明IGF-ⅡLOI的发生与肾细胞癌的病理类型及年龄相关性不大.本实验涉及的30例肾细胞癌中,按照TNM分类,8例T1期肾细胞癌中有6例(75%)癌及其相应癌旁组织均发生了IGF-Ⅱ的LOI,1例(12.5%)在癌组织中发生IGF-ⅡLOI,但其相应癌旁组织中IGF-Ⅱ印迹正常.结论:IGF-ⅡLOI可能是肾细胞癌的早期发生事件,可能对其早期发生有重要作用.
Objective: To investigate the imprinting status of IGF- Ⅱ gene in renal cell carcinoma and its relationship with the progression of renal cell carcinoma. Methods: Renal cell carcinoma tissues and matched histologically normal kidney tissues of 30 patients were collected. Based on a polymorphism ofApa I site in exon 9 of IGF- Ⅱ, polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis was used to select the heterozygous allele. Loss of imprinting of IGF- Ⅱ was further examined with RT-PCR-PFLP technique. Results: There were 19 renal cell carcinoma (:ases with heterozygous IGF-Ⅱ gene (63.3%, 19/30). And in these 19 case, 13 cases had loss of imprinting of IGF- Ⅱ gene (68.4%, 13/19)in carcinoma tissues and matched histologically normal kidney tissues, and 1 case had loss of imprinting of IGF- Ⅱ gene only in carcinoma tissues (5.3%, 1/19). Of the 22 cases of clear cell renal cell carcinoma, 10 cases had loss of imprinting of IGF- Ⅱ gene in carcinoma tissues and matched histologically normal kidney tissues (45.45%, 10/22). Of the 5 cases of papillary renal cell carcinoma, 2 cases had loss of imprinting of IGF- Ⅱ gene in carcinoma tissues and matched histologically normal kidney tissues (40%, 2/5). Of the 2 cases of chromophobe renal cell carcinoma, 1 case had loss of imprinting of IGF-Ⅱ gene in carcinoma tissues and matched histologically normal kidney tissues. The 1 case of mucinors tubular and spindle cell carcinoma had loss of imprinting of IGF- Ⅱ gene only in carcinoma tissues. Of the 8 T1 stage heterozygous renal cell carcinoma cases, 6 cases (75%) had loss of imprinting of IGF- Ⅱ gene in carcinoma tissues and matched histologically normal kidney tissues, and 1 case (12.5%) had loss of imprinting of IGF- Ⅱ gene only in carcinoma tissues. Cenclusion: Loss of imprinting of IGF- Ⅱ gene may be an early event of renal cell carcinoma and may play an important role in the development of renal cell carcinoma.