卵巢肿瘤中c-kit基因突变的临床研究

Analysis of c-kit mutations in ovarian epithelial tumors

目的探讨c-kit基因在卵巢恶性上皮性肿瘤中的突变情况及其在卵巢肿瘤发生发展中的作用。方法2004年1月至2005年12月在哈尔滨医科大学附属第一临床医学院、第三临床医学院应用PCR扩增和基因测序的方法检测卵巢恶性上皮性肿瘤、卵巢交界性肿瘤、卵巢良性肿瘤及正常卵巢组织中c-kit基因第11号外显子序列。结果c-kit基因在卵巢恶性上皮性肿瘤、卵巢交界性肿瘤、卵巢良性肿瘤及正常卵巢组织中的突变率分别为72.1%、44.4%、11.5%、0,卵巢恶性上皮性肿瘤及交界性肿瘤中c-kit基因突变率均高于卵巢良性肿瘤及正常卵巢组织,差异有显著性意义(P<0.05)。卵巢恶性上皮性肿瘤与卵巢交界性肿瘤中c-kit基因突变率差异无显著性意义(P>0.05)。在卵巢恶性上皮性肿瘤中,低分化组的c-kit基因突变率为88.9%,明显高于中、高分化组(P<0.05),c-kit基因的突变率随FIGO分期的进展及淋巴结的转移而升高(P<0.05),c-kit基因的突变与卵巢肿瘤的病理类型无关(P>0.05)。结论c-kit基因突变在卵巢恶性上皮性肿瘤的发生发展中可能发挥重要作用,可作为诊断卵巢良恶性肿瘤的参考指标。c-kit基因突变与卵巢恶性上皮性肿瘤的预后有关,可作为判断卵巢恶性上皮性肿瘤患者预后的指标之一。

Objective To define the frequency and spectrum of c-kit gene mutations in ovarian epithelial tumors and the relationship of their mutations with the development of ovarian epithelial carcinoma. Methods Seventy-eight cases of ovarian tissues from Jan. 2004 to December 2005 Harbin Medical University Affiliated First Clinical Hospital and Affiliated Third Clinical Hospital （8 normal ovarian tissues, 18 benign ovarian epithelial tumors, 9 borderline ovarian epithelial tumors and 43 ovarian epithelial carcinoma） were examined for mutations in exon 11 of c-kit gene using PCR amplification and DNA sequencing. Results Thirty-one of 43 ovarian epithelial carcinoma（ 72. 1% ） and 4 of 9 borderline ovarian epithelial tumors（44.4% ） revealed mutations in exon l lof c-kit gene. Only 3 of 18 benign ovarian epithelial tumors （ 11.5% ） revealed mutations and none of 8 normal ovarian epithelial tumors（ 0 ） revealed mutations. The mutation rate of c-kit in ovarian epithelial carcinoma was statistically higher than those in normal ovarian and benign ovarian epithelial tumors（ P 〈 0. 05）. The mutations rate of borderline ovarian epithelial tumors was also statistically higher than those in normal ovarian and benign ovarian epithelial tumors（ P 〈 0.05 ）. Thirty-one of 43 ovarian epithelial carcinoma revealed the mutations of c-kit gene. Most of the mutations consisted of in-frame deletion or a Point mutations. The mutation rate of c- kit in low differentiated grade group was higher than that in high and middle differentiated grade group（ P 〈 0.05 ）, rising it rises with the development of FIGO clinical stages and lymphatic metastasis（P 〈0. 05）. The mutation of c-kit had no relationship with the pathological types of the ovarian epithelial tumors （P 〉 0.05）. Conclusion The mutations of c-kit gene might partially represent one of the molecular mechanisms of ovarian epithelial carcinoma, and probably play an im- portant role in the generation and development of ovarian epithelial carcinoma. It can be used as a marker for distinguishing benignancy and malignancy of ovarian epithelial tumors. The mutation of c-kit relates to the clinical results of ovarian epithelial carcinoma; gene c-kit may be a predictable factor.