ER阳性乳腺癌PR亚型与C-erbB-2表达关系的研究

Association between progesterone receptor isoforms A and B and HER-2/neu expression in estrogen receptor-positive breast cancers

目的研究雌激素受体(ER)和孕激素受体(PR)阳性乳腺癌孕激素受体亚型(PR-A、PR-B)的表达,探讨PR-A、PR-B及其比值(PR-A/PR-B,A/B)与表皮生长因子受体-2(C-erbB-2,Her-2/neu)表达的关系及对无病生存期的影响。方法选取该科2001年3月～2003年10月手术治疗ER、PR阳性乳腺癌65例,癌组织标本采用免疫组织化学SP法检测PR-A、PR-B表达状态,半定量法判定结果,运用SPSS13.0统计软件包及χ2检验进行结果处理,Kaplan-Meier法描述生存曲线。结果PR-A、PR-B阳性表达物位于细胞核中,细胞质及细胞膜无表达;乳腺癌孕激素受体亚型PR-A阳性表达占90.77%(59/65)、PR-B占58.46%(38/65)(P<0.05)。59例PR-A阳性表达乳腺癌中,C-erbB-2阳性48例(81.36%),阴性11例(18.64%)(P<0.01);39例PR-A/PR-B(A/B)值>1的患者中,C-erbB-2阳性33例(84.62%),阴性6例(15.38%)(P<0.05)。在C-erbB-2阳性表达乳腺癌中,A/B值>1的患者无病生存期明显低于A/B值≤1的患者(P<0.05),而C-erbB-2阴性表达时两组的无病生存期差异无显著性(P>0.05)。结论在雌、孕激素受体阳性乳腺癌中,孕激素受体亚型PR-A表达高于PR-B表达,且A/B值增高(>1)。在C-berB-2阳性表达的乳腺癌中,A/B值>1时临床预后差,预示对三苯氧胺治疗不敏感。

[Objective] To study the expression of PR-A and PR-B in breast cancers with positive pregesterone and estrogen receptor and explore the correlation between the expression of C-erbB-2 （Her-2/neu） and PR-A and PR-B as well as their ratio, the influence of PR-A and PR-B ratio on the progenosis of expression of Her-2/neu is also discussed in breast cancers. [Methods] 65 cases of paraffin fixing samples of breast cancer with ER, PR positive and foUow-up dates was collected in our mammary department between March 2001, and October 2003. The expression of PR-A and PR-B was detected by IHC-SP method. Statistical analysis was performed using SPSS soft- ware version 13.0. [Results] All the positive staining of PR-A and PR-B is located in the cell nucleus, not in the cell membrane and cytoplasm. Among the 65 patients of ER and PR positive breast cancer, PR-A was positive expresion in 90.77% （59/65）, which was higher than PR-B 58.46%（38/65） （P 〈0.05）. In the 59 patients of PR-A positive expression, the 48 （81.36%） patients of C-erbB-2 positive express was higher than 11 （18.64%） patients of negative （P 〈0.01）. In the 39 eases of the ratio of PR-A and PR-B 〉1, the 33 （84.62%） eases of C-erbB-2 positive expression was higher, 6 （15.38%） cases negative （P 〈0.05）. There is significant difference between the ratio of PR-A and PR-B and disease free survival （DFS） in the breast cancer with the positive expression of C-erbB-2. The DFS was lower in breast cancer patients with high ratio of PR-A and PR-B （〉1） than that with low ratio of two isoforms （≤ 1）, which is significantly different （P 〈0.05）. [Conclusion] The expression level of PR-A is higher than PR-B and the ratio of PR-A and PR-B is increasing in patients with ER,PR positive breast cancer. The higher ratio of PR-A and PR-B may indicate poorer response to Tamoxifen endocrine therapy in the breast cancer patients with C- erbB-2 positive expression.