错配修复基因hMLH_1和hMSH_2蛋白在正常皮肤黑素细胞痣和皮肤恶性黑素瘤中的检测

目的检测DNA错配修复基因hMLH1和hMSH2蛋白在正常皮肤、黑素细胞痣和皮肤恶性黑素瘤(CMM)中的水平,探讨其在皮肤黑素瘤发生、发展中的可能作用。方法用免疫组化SP法检测20例正常皮肤、30例黑素细胞痣和57例原发性CMM中hMLH1和hMSH2蛋白的水平。结果①正常皮肤的表皮、皮肤附属器和黑素细胞痣的细胞核中,hMLH1和hMSH2蛋白强阳性,这两种蛋白在正常皮肤和黑素细胞痣无显著性差异(P>0.05);②在57例CMM中,hMLH1蛋白阳性35例(61.40%),hMSH2蛋白阳性32例(56.14%),这两种错配修复蛋白在CMM中的阳性率和阳性强度显著低于其在正常皮肤和黑素细胞痣中的水平(P均<0.005);③在CMM中,随Clark分级升高,hMLH1和hMSH2蛋白的阳性率和阳性强度逐渐降低。结论错配修复基因hMLH1和hMSH2蛋白在维护正常皮肤和皮肤附属器细胞基因组稳定性中可能发挥了重要作用,其异常可能参与了CMM发生和发展的过程。

Detection of Mismatch Repair Genes hMLH1 and hMSH2 in Normal Skin,Melanocytic Nevus and Cutaneous Malignant Melanoma

Objective To study the level of mismatch repair genes hMLH 1 and hMSH 2 protein in normal skin,melanocytic nevus and cutaneous malignant melanoma (CMM) and to explore their relationship to clinicopathological significance of skin melanocytic tumour.Methods Immunohistochemistry streptomycin peroxidel method was used to detect the hMLH 1 and hMSH 2 proteins in 20 normal skin specimens,30 melanocytic nevus specimens and 57 primary CMM samples.Results ① hMLH 1 and hMSH 2 proteins showed strongly staining in the nuclear of normal epidermis,skin adnexal structures and melanocytic nevus,both mismatch repair proteins showed no significantly difference between normal skin and melanocytic nevus specimens( P >0.05); ② In 57 cases of CMM, hMLH 1 protein was observed in 35(61.40%), hMSH 2 protein was observed in 32(56.14%),the positive rate and positive intensity of the two proteins in CMM were significantly lower than those in normal skin and melanocytic nevus( P <0.005); ③In CMM,as the Clark grade increased,the positive rate and percent of positive cell,staining intensity and immunoactivity score of hMLH 1 and hMSH 2 proteins decreased. Conclusion Mismatch repair genes hMLH 1 and hMSH 2 might play important role in maintaining stability of genome in normal skin and adnexal structures,abnormal hMLH 1 and hMSH 2 proteins may be involved in the carcinogenesis process and progression of CMM.