燃煤型砷中毒皮肤病变中P16、P21^(WAF1/CIP1)、CyclinD1蛋白的表达及意义

The expression of P16、P21^(WAF1/CIP1)and Cyclin D1 proteins in skin of patients with arseniasis caused by coal burning and their significance

目的 探讨砷中毒与皮肤病变的关系。方法 用免疫组织化学法检测燃煤型砷中毒患者皮肤病变中P16、P2 1WAF1/CIP1、CyclinD1蛋白的表达情况。结果 P16的表达强度和密度随患者皮肤病变程度的加重而逐渐减弱 ,P16蛋白在癌变组 (A组 )、癌前病变组 (B组 )和过度角化组 (C组 )中普遍缺失表达 ,明显低于一般增生病变组 (D组 )和正常组 ;P2 1WAF1/CIP1、CyclinD1的表达强度和密度随患者皮肤病变程度的加重而逐渐加强 ,P2 1WAF1/CIP1在各病变组中普遍强表达 ,明显高于正常组 ,各病变组间也有不同程度的差异 ;CyclinD1在A、B、C组中普遍强表达 ,明显高于D组和正常组。以上差异具有统计学意义。结论 皮肤过度角化可能是皮肤癌变的先兆 ;P16和CyclinD1蛋白的异常表达可作为皮肤癌变的预警标志 ;P16、P2 1WAF1/CIP1和CyclinD1在燃煤型砷中毒致皮肤病变尤其癌变的过程中共同起重要作用 ,动态监测P16、P2 1WAF1/CIP1和CyclinD1蛋白的表达水平有助于砷中毒致皮肤癌的早期发现。

Objective To study the relationships between arseniasis and skin carcinoma. Methods The expressions of p16、p21 WAF1/CIP1 and Cyclin D1 proteins in skin of arsenic intoxication patients caused by coal burning was measured by immunohistochemistry methods. Results The intensity and density, and the positive percentage of p16 protein were gradually reduced as the skin pathological changes progressed. Expressions of p16 protein was lower in the carcinoma group (A group), pre carcinoma group (B group) and overkeratosis group (C group) than the general cell proliferation group (D group) and normal group ( P < 0 05, P < 0 01). On the other hand, the cell density and the positive percentage of p21 WAF1/CIP1 and Cyclin D1 proteins were gradually increased as the skin pathological changes progressed. The expression of p21 WAF1/CIP1 protein in all pathological groups were higher than the normal group ( P< 0 05, P< 0 01), and expression of CyclinD1 protein in A, B and C groups were higher than the D group and normal group ( P< 0 05, P< 0 01). Conclusions Skin overkeratosis may be the earlier stage of skin carcinoma, lower expression of p16 protein and overexpression of Cyclin D1 protein may be considered as prognostic biomarkers to skin carcinogesis; p16, p21 WAF1/CIP1 and Cyclin D1 may play important role in the cooperative way in the development of arseniasis caused by coal burning and further progression to skin carcinoma. Monitoring of the expression of p16, p21 WAF1/CIP1 and Cyclin D1 proteins may be valuable for early detection and early treatment and prognostic assessment of skin carcinoma caused by coal burning.