K-ras基因第1外显子点突变与37例子宫内膜癌临床情况的关系

Relationships between the mutation of K ras gene exon 1 and the clinical conditions of endometrial carcinoma

目的：研究中国子宫内膜癌患者的瘤组织中Ｋｒａｓ基因第１外显子（含第１２，１３密码子）的突变率，以及突变与子宫内膜癌临床情况的关系，探讨Ｋｒａｓ基因突变在子宫内膜癌发生中的作用。方法：３７例子宫内膜癌的石蜡和部分冰冻标本行ＰＣＲ扩增Ｋｒａｓ基因第１外显子（含第１２，１３密码子），经ＰＣＲＳＳＣＰ银染法检测突变。结果：３７例子宫内膜癌患者中有１２例存在Ｋｒａｓ基因突变，突变率为３２．４％（１２／３７例）。ＦＩＧＯ分期Ⅲ期、组织类型为腺鳞癌的患者突变率较高，在细胞低分化、侵肌１／２以上和绝经后的患者中突变比例也较高。石蜡和冰冻组织标本结果一致。结论：Ｋｒａｓ基因突变率在日、美两国内膜癌患者中不同。该组患者中的突变率与日本相似，高于美国。说明此种差异不仅存在于日本和美国患者之间，可能也存在于亚洲人与北美洲人之间。不同的基因背景，生活条件及内源性和外源性雌激素作用可能对Ｋｒａｓ基因突变率有影响，并引起了不同的临床表现。

Objectives:To detect the mutation rate of exon 1 of the K ras gene (including codons 12 and 13) and clinical significance of such mutations in Chinese patients suffering from endometrial carcinoma, to disclose the relationships between the mutation and the clinical history, the clinical states, as well as the prognosis. Methods: Surgical treatments were given to 37 cases of endometrial carcinoma. DNA's were extracted from the formalin fixed, paraffin embedded tissue sections (6 of them had frozen sections simultaneously) and then amplified by polymerase chain reaction (PCR) for K ras gene exon 1 (including codons 12 and 13). Single strand conformation polymorphism (SSCP) with silver staining was taken to analyze the mutation. Results: 12 cases of endometrial carcinoma were found to have exon 1 mutation of K ras with the mutant rate being 32.4%. There were statistically higher mutation rates in stage Ⅲ or adenosquamous type, and more cases were in low grade, myometrial invasion (over 1/2), and menopause. Similar results were obtained in paraffin embedded and frozen sections. Conclusion: The mutation rates of K ras oncogene in the Japanese and American were different as reported before. The mutation rate was similar to that of the Japanese and was more frequent than that of the American. It suggests: (1)Such difference may also exist between the Asian and American. (2)Different genetic background, living conditions and endogenous or exogenous estrogen may affect the mutation rate of K ras oncogene, which possibly influence the different clinical and pathological conditions.