cyclin D1, cyclin E 在乳腺良、恶性病变中的表达及其与p16,p21waf1及Rb 蛋白的关系

为探讨cyclinD1,cyclinE在乳腺癌发生发展中的作用及其与细胞周期调控相关基因蛋白的关系,采用免疫组化检测17例非增生乳腺导管上皮、19例不同程度增生的导管上皮及59例乳腺癌中cyclinD1,cyclinE,p16,p21waf1及Rb基因蛋白的表达.结果显示1.非增生乳腺导管上皮除1例cyclinE过表达外均无cyclinD1和cyclinE的过表达.乳腺癌的cyclinD1和cyclinE的过表达率均明显高于良性乳腺组织(P<0.05).2.乳腺癌cyclinD1过表达与淋巴结转移呈正相关(P<0.05),瘤体直径大于5cm者cyclinE过表达呈增加趋势,但差异无显著性意义.3.CyclinD1和cyclinE的过表达呈正相关(P<0.05).4.从非增生乳腺导管上皮到增生直至乳腺癌,p16,p21与cyclinD1,cyclinE含量的比值逐渐递减,而p21含量高于cyclinD1的乳腺癌体积小、淋巴结转移率低(P<0.05).p21阳性率与cyclinD1过表达呈正相关(P<0.01),也随cyclinE的过表达呈上升趋势.Rb基因蛋白的强表达与cyclinD1过表达呈正相关(P<0.01).结果表明CyclinD1和cyclinE蛋白过表达频发于乳腺癌早期,它们可能与p16、p21waf1、pRb共同参与了乳腺癌的发生发展.

EXPRESSION OF CYCLIN D1, CYCLIN E IN BENIGN AND CANCEROUS BREAST TISSUESAND TH EIR RELATIONSHIPS WITH P16, P21waf1 AND RETINOBLASTOMATUMOR SUPPRE SSOR PROTEIN

In order to explore the effects of G1 S cell cycle regulating proteins on mammary carcinogenesis and progression, cyclin D1, cyclin E, p16, p 21 waf1 and pRb expressions were examined immunohistochemically in 36 benign breast tissues, including 17 cases without and 19 with epithelial hyperplasia, and 59 breast carcinomas. No overexpression for cyclin D1 and cyclin E was detected in duct epithelia without hyperplasia except one case with cyclin E overexpression. The positive rates of cyclin D1 and cyclin E in breast cancer were significantly higher than those in benign tissues( P <0 05). There was a positive correlation between cyclin D1 overexpression and lymph node involvement( P <0 05), and there was a trend for tumors larger than 5cm to overexpress cyclin E more frequently. A positive correlation was evident between overexpression of cyclin D1 and cyclin E( P <0 05). The ratios of p16 and p21 to cyclin D1 and cyclin E contents decreased from normal breast epithelia, hyperplasia to carcinomas. Tumors with higher p21 than cyclin D1 content were smaller in size and had lower frequency of node involvement( P <0 05). p21 positivity was correlated with cyclin D1 overexpression( P <0 01),and there was a trend to ward more cyclin E overexpression with the increasing expression of p21. Strong expression of pRb was positively associated with cyclin D1 overexpression ( P <0 01). The results suggest that cyclin D1 and cyclin E overexpressions occur in the early stage of breast carcinoma, which might play an important role in the transformation and development of breast cancer cooperating with genes of p16, p21waf1 and Rb.