Ki67、增殖细胞核抗原在不同分子分型乳腺癌组织中的表达及意义

目的探讨Ki67、增殖细胞核抗原（PCNA）在不同分子类型乳腺癌组织中的表达及临床意义。方法采用免疫组化法检测251例乳腺癌组织中Ki67、PCNA的表达情况，采用kruskal—wallis秩和检验分析Ki67、PCNA在不同分子类型乳腺癌组织中的表达差异；采用Spearman相关分析法，分析不同分子类型中Ki67与PCNA表达的相关性及其分别与原发肿瘤直径、腋窝淋巴结转移及病理组织学分级的相关性；采用生存分析法，分析Ki67、PCNA对乳腺癌预后的意义。结果Luminal型、HER-2型及三阴性乳腺癌组织中Ki67、PCNA表达强度差异均无统计学意义（X^2=3．722，P=0．155；）（X^2=5．135，P=0．077）。Ki67与PCNA总体呈正相关（r1=0．348，P=0．000），在Luminal型中呈正相关（r3=0．467，P=0．000），而在HER-2型、三阴性乳腺癌中无相关性（P〉0．05）。Ki67表达强度与原发肿瘤直径、腋窝淋巴结转移及组织学分级在Luminal型乳腺癌呈正相关性（r1=0．180，P：0．017；rs=0．236，P=0．002；0=0．156，P=0．039），而在HER-2型及三阴性乳腺癌中无相关性（P〉0．05）。PCNA表达强度与Luminal型乳腺癌的腋窝淋巴结转移呈正相关性（r1=0．166，P=0．028），与HER-2型乳腺癌的原发肿瘤直径呈负相关性（r1=-0．342，P=0．020），与其他病理因素均无相关性（P〉0．05）。单因素生存分析显示腋窝淋巴结转移、组织学分级对乳腺癌患者无瘤生存有影响（HR=4．431，95％CI：1．787～10．984；HR=2．492，95％C，：1．032～6．018），亚组分析显示腋窝淋巴结、PCNA对Luminal型乳腺癌患者无瘤生存有影响（HR=3．930，95％C1：1．343～11．501；HR=2．401，95％C1：1．044—5．524）。多因素COX回归分析显示腋窝淋巴结转移是总体和Luminal型乳腺癌患者预后的独立影响因素（HR=3．780，95％CI：1．461—9．775；HR=3．403，95％CI：1．150～10．075）。结论Ki67和PCNA对评估Luminal型乳腺癌预后有一定指导意义，而对HER-2型和三阴性乳腺癌预后无明显影响。

Expression of Ki67 and proliferating cell nuclear antigen in different subtypes of breast cancer and their clinical significance

Objective To investigate the expression of Ki67 and proliferating cell nuclear antigen （PCNA） in three different subtypes of breast cancer and their clinical significance. Methods Immunohistoehemistry was used to detect the expression of Ki67 and PCNA in tissue samples from 251 breast cancer patients, kruskal-wallis rank sum test was used to analyze the expression difference of Ki67 and PCNA in different subtypes, Spearman rank test for the correlation of their expressions, and the correlation with primary tumor diameter, axillary lymph node metastasis and pathological classification, respectively. Meanwhile, the survival analysis was conducted to display the prognostic value of Ki67 and PCNA expression. Results The expressions of Ki67 and PCNA were not significantly different among the three subtypes of breast cancer （luminal, HER-2 and triple negative） （ X^2 = 3.722, P = 0. 155 ;X^2 = 5. 135, P = 0. 077 ）. There was a positive correlation between Ki67 and PCNA expressions in general（ re = 0. 348 ,P〈0. 001 ） and in luminal subtype（ r, = 0. 467, P〈0. 001 ）, but no correlation was observed in other subtypes（P〉0. 05）. In luminal subtype, the expression of Ki67 was positively correlated with primary tumor diameter, axillary lymph node status and histological grade （rs=0. 180,P=0. 017;rs =0. 236,P= 0. 002;r1=0. 156,P=0. 039, respectively）, and no correlation was showed in HER-2 and triple-negative subtypes （P〉 0. 05 ）. We also observed the positive correlation between PCNA expression and axillary lymph node status in luminal subtype, a negative correlation with primary tumor diameter in HER-2 subtype （ rs = - 0. 342, P = 0. 020）, but no correlations with other pathological factors were found （ P 〉 0. 05 ）. Univariate analysis showed axillary lymph node metastasis and nuclear grade had influence on tumor-free survival of breast cancer patients （HR=4. 431, 95% CI： 1. 787 to 10. 984; HR = 2.492, 95% CI： 1.032 to 6.018）. The subgroup analysis displayed axillary lymph node metastasis and PCNA had effects on tumor-free survival in luminal subtype （HR = 3. 930, 95% CI： 1. 343 to 11.501; HR= 2.401, 95% CI： 1.044 to 5. 524）. Multivariate COX analysis showed axillary lymph node metastasis was an independent prognostic factor in general and luminal subtype breast cancer patients （HR = 3. 780, 95%C1：1.461 to 9. 775; HR=3.403,95%CI： 1. 150 to 10. 075）. Conclusion Ki67 and PCNA can indicate the poor prognosis of luminal subtype breast cancer patients to a certain extent, but have no influence on HER-2 and triple negative subtypes.