乳腺乳头状瘤病中4种细胞周期调控因子的检测及临床意义

The clinical significance of the expression of four cell cycle regulators in breast papillomotosis

目的 观察不同程度的乳腺乳头状瘤病中 4种细胞周期调控因子蛋白的表达及临床意义 ,为临床上乳腺癌癌前病变的有效诊治提供客观指标。方法 通过免疫组织化学S P法在乳腺轻度、中度、重度乳头状瘤病及导管内癌组各 4 8例患者中检测细胞周期素D1、p16、E2F 1、Rb基因蛋白表达情况。结果 细胞周期素D1、p16、E2F 1、Rb 4种因子表达的阳性率和表达强度分别在 4组间的差异均有显著意义 (χ2 分别为 16 70、2 0 74、4 0 34、4 2 32 ;19 12、2 9 4 7、4 5 0 8、4 6 92 ,均P <0 0 1;在中度和重度乳头状瘤病组间差异也有显著意义 (均P <0 0 5 ) ;E2F 1或Rb在重度乳头状瘤病和导管内癌组间差异有显著意义 (均P <0 0 1) ,但细胞周期素D1或 p16在这两组间差异无显著意义 (均P >0 0 5 ) ;细胞周期素D1及E2F 1表达与由轻至重的乳头状瘤病乃至导管内癌呈正相关 ,相反p16及Rb与之呈负相关 ;Rb阴性或低表达时中度乳头状瘤病发展到重度乳头状瘤病的危险度最大。结论细胞周期素D1等 4种调控因子与乳腺癌的发生发展过程有密切的相关性。E2F 1和Rb可作为重度乳头状瘤病和导管内癌鉴别诊断的参考指标。Rb还有助于筛选重度和中度乳头状瘤病中的高危病例。

Objective To investigate the clinical significance of the protein expression of 4 cell cycle regulators in papillomatosis of the breast. Methods Immunohistochemistry was used to examine the protein expression of CyclinD1, p16, E2F-1 and Rb in 4 groups (196 cases) with mild papillomatosis (MP), moderate papillomatosis (MoP), serious papillomatosis (SP) and ductal carcinoma in situ (DCIS). Results There were significant difference of the positive rate and the intensity of CyclinD1, p16, E2F-1 and Rb expression among the groups, respectively (χ 2 were 16.702, 20.742, 40.335, 42.317; 19.120, 29.469, 45.080, 46.920, P <0.01. Meaning time there were significant difference in the expression of these 4 factors between MoP and SP ( P <0.05). There was significance of E2F-1 or Rb expression between SP and DCIS ( P <0.01), but there was no significance to be found in the expression of CyclinD1 or p16 between the two groups( P >0.05). Rb was screened as the highest risk factor by Odd Risk Logistic Analysis. Conclusion CyclinD1, p16, E2F-1 and Rb played the important roles from MP into SP and then DCIS. E2F-1 and Rb can be used as the assistant indictors on the differentiation of SP and DCIS. Rb may be helpful in screening high risk cases from SP or MoP.