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耐药蛋白P-gp、BCRP及LRP在乳腺癌原发灶和腋淋巴结转移灶中表达的比较
刘新兰1*,黄英2,李云霞1,段瑜2
0
(1. 宁夏医科大学附属医院肿瘤内科, 银川 750004;
2. 宁夏医科大学临床医学院肿瘤学系, 银川 750004
*通信作者)
摘要:
目的 研究P-糖蛋白(P-glycoprotein,P-gp)、乳腺癌耐药蛋白(breast cancer drug resistance protein,BCRP)和肺耐药蛋白 (pulmonary resistance protein,LRP)在乳腺癌原发灶和腋淋巴结转移灶中表达的差异。 方法 采用免疫组织化学染色法检测126例乳腺癌患者的原发灶和66例腋淋巴结转移灶中P-gp、BCRP、LRP的表达。 结果 (1)P-gp、BCRP及LRP在乳腺癌原发灶中的阳性表达率分别为41.27%(52/126)、38.89%(49/126)、65.87%(83/126),在腋淋巴结转移灶中阳性表达率分别为59.09% (39/66)、63.64%(42/66)、60.61%(40/66)。P-gp、BCRP在乳腺癌淋巴结转移灶中的表达高于原发灶(P<0.05),LRP在原发灶和淋巴结转移灶之间的表达差异无统计学意义。(2)P-gp、BCRP在乳腺癌原发灶和腋淋巴结转移灶中表达差异没有统计学意义(P<0.01) ,Kappa值分别为0.276、0.356;LRP在原发灶和淋巴结转移灶中的表达差异没有统计学意义(P>0.05)。(3)乳腺癌原发灶中2个耐药蛋白共表达率为35.71%(45/126),3个耐药蛋白同时表达的阳性率为15.08%(19/126),有2个或3个耐药蛋白共表达率为50.79%(64/126),高于单独阳性表达率33.33%(42/126,P<0.05)。腋淋巴结转移灶中2个耐药蛋白共表达率为53.03%(35/66),高于单独阳性表达率(27.27% ,P<0.05);3个耐药蛋白同时表达的阳性率为16.67% (11/66),有2个或3个耐药蛋白共表达率为69.70%(46/66),高于单独阳性表达率 (P<0.01)。腋淋巴结转移灶中2个耐药蛋白共表达率及2个或3个耐药蛋白共表达率均高于乳腺癌原发灶中的表达(P<0.05)。(4)Kaplan-Meier生存分析结果表明,乳腺癌腋淋巴结转移灶中P-gp、BCRP及LRP阳性表达者5年总生存期较原发灶耐药蛋白阳性者低(P<0.05)。 结论 在乳腺癌原发灶和腋淋巴结转移灶中的P-gp、BCRP表达差异有统计学意义,LRP表达则没有明显差异;多个耐药蛋白共表达协同作用为耐药的主要特征,腋淋巴结转移灶中可能具有更强的耐药性。
关键词:  乳腺肿瘤  腋淋巴结转移灶  P糖蛋白  乳腺癌耐药蛋白  肺耐药蛋白
DOI:10.3724/SP.J.1008.2011.01171
投稿时间:2011-07-14修订日期:2011-10-09
基金项目:宁夏高等学校科学研究项目(2006014).
Expressions of resistance proteins P-gp, BCRP and LRP: a comparison between primary and metastatic breast carcinoma
LIU Xin-lan1*,HUANG Ying2,LI Yun-xia1,DUAN Yu2
(1. Department of Oncology, Affiliated Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China;
2. Department of Oncology, Clinical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China
*Corresponding author.)
Abstract:
Objective To investigate the differences in expressions of P-glycoprotein (P-gp), breast cancer drug resistance protein (BCRP) and pulmonary resistance protein (LRP) between primary breast carcinoma and metastatic lymph nodes. Methods The expressions of P-gp, BCRP and LRP in breast cancer tissues, including 126 primary carcinoma and 66 metastasis lymph nodes, were determined immunohistochemically on formalin-fixed, paraffin-embedded tumor sections. Results (1)The positive expression rates of P-gp, BCRP and LRP were 41.27%(52/126), 38.89%(49/126),and 65.87%(83/126) in primary breast carcinoma, and were 59.09% (39/66),63.64%(42/66),and 60.61%(40/66) in metastatic lymph nodes, respectively. The positive rates of P-gp and BCRP in the metastatic lymph nodes were significantly higher than those in primary cancer tissue(P<0.05); there was no significant difference in expression of LRP (P>0.05) .(2) There was a poor consistency in P-gp and BCRP expression between the primary and metastatic sites(P<0.01, Kappa value were 0.276 and 0.356); there was a consistency in LRP expression between the primary and metastatic sites(P>0.05).(3) The co-expression rate of two resistance proteins in primary breast carcinoma was 35.71%(45/126), of three resistance proteins was 15.08%(19/126), and of two or three resistance proteins was 50.79%(64/126), being significantly higher than that of a single protein 33.33% (42/126,P<0.05). The co-expression rate of two resistance proteins in metastasis lymph nodes was 53.03%(35/66), which was significantly higher than that of a single protein 27.27%(18/66,P<0.05). The co-expression rate of three resistance proteins was 16.67%(11/66), two or three resistance proteins was 69.70%(46/66), which was significantly higher than that of a single protein (P<0.01). Both the co-expression levels of two resistance proteins and two or three resistance proteins in metastatic lymph nodes were significantly higher than those in primary cancer (P<0.05) .(4)Kaplan-Meier analyses revealed that patients with P-gp, BCRP and LRP expressed in the metastatic lymph nodes had a lower 5-year survival rate compared with patients whose primary breast cancer being positive for them. Conclusion The expression of P-gp and BCRP is different between the primary and metastatic breast cancer sites, and there is no significant difference in LRP expression. Coordination of multi-protein expression is a major feature of resistance. Metastasis lymph nodes may have a stronger resistance.
Key words:  breast neoplasms  metastatic lymph nodes  P-glycoprotein  breast cancer drug resistance protein  pulmonary resistance protein