摘要目的 探讨年轻女性乳腺癌分子标志物的表达特征及其临床病理意义,为提高其早期诊断及合理的临床治疗提供依据.方法 采用组织芯片技术及免疫组织化学SP法对107例年轻组(≤35岁)和112例年老组(≥60岁),共219例乳腺浸润性导管癌患者的乳腺癌易感基因(BRCA)1和WWOX蛋白表达进行检测,并分析其与各临床病理指标的关系.另收集2008年该院手术切除的年轻(≤35岁)女性乳腺浸润性导管癌新鲜组织标本10例,同时采用PCR扩增和直接测序法检测BRCA1基因外显子2和20突变情况.结果 BRCA1蛋白阳性表达率年轻组的65.4％ (70/107)高于年老组的35.7％ (40/112),两组间雌激素受体(ER)、孕激素受体(PR)、HER2和WWOX蛋白的表达率及Ki-67高阳性指数的比率之间差异无统计学意义(均P＞0.05).BRCA1表达与pTNM分期及腋窝淋巴结转移呈正相关(均P＜0.05),与ER、PR、HER2、WWOX蛋白表达、Ki-67高阳性指数比率及组织学分级无相关性(均P＞0.05).WWOX蛋白表达与各临床病理指标之间无相关性(均P＞0.05).未检测到BRCA1基因外显子2和20位点突变,考虑与样本量较少有关.结论 BRCA1胞质表达与年轻乳腺癌的发生、发展及预后密切相关.

abstractsObjective To explore the clinicopathologic characteristics and biological markers of breast carcinomas in young women.Methods Immunohistochemical SP method was used to study breast cancer susceptibility gene (BRCA1) and WWOX in breast carcinomas of patient ≤35 years of age (107 cases) and ＞60 years of age (112 cases).The findings were correlated with clinicopathological features.In addition,PCR amplification and direct sequencing were performed to detect the BRCA1 gene mutation of exons 2 and 20 using fresh frozen tissue samples in other 10 patients who were ≤35 years of age.Results The positive rate of BRCA1 protein expression was higher in the young age group [65.4％ (70/107)] than that of the old age group [35.7％ (40/112)].ER,PR,HER2,and WWOX protein expression and proliferation marker Ki-67 were no statistically different in the two groups (all P ＞ 0.05).BRCA1 expression was significantly correlated with pTNM and axillary lymph node metastasis (both P ＜ 0.05),but not with ER,PR,HER2 and WWOX protein expression (all P ＞ 0.05).Ki-67 and histological grading showed no statistical correlation (P ＞ 0.05).WWOX protein expression showed no correlation with clinicopathologic characteristics (all P ＞ 0.05).Mutation of exons 2 and 20 of the BRCA1 gene was not detected in any of 10 cases studied.Conclusion BRCA1 cytoplasmic expression statistically correlates with the development and prognosis of breast cancer of young patients.