survivin、p53及人表皮生长因子受体2在乳腺癌组织中的表达及预后判断价值

Expressions of survivin,p53 and human epidermal growth factor receptor 2 in breast cancer tissues and their prognostic value

目的探讨细胞凋亡相关因子survivin、p53及人表皮生长因子受体2(HER2)在乳腺癌组织中的表达及对预后判断的价值。方法前瞻性选择2015年2月至2019年1月唐山市妇幼保健院收治的131例行乳腺癌根治术患者为研究对象,术中采集患者癌组织和癌旁组织(距离肿瘤边缘>3 cm的正常组织)。采用免疫组织化学法检测患者癌组织和癌旁组织survivin、p53、HER2表达情况。记录随访3年内患者预后情况,其中复发、转移、死亡定义为预后不良,其余为预后良好;比较预后不良组和预后良好组间临床病理特征差异。采用多因素logistic回归分析乳腺癌患者预后危险因素。以乳腺癌预后结果为金标准,采用受试者工作特征(ROC)曲线分析survivin阳性、p53阳性、HER2阳性单独、两两联合及三者联合判断患者预后不良的价值。结果癌组织survivin阳性表达率[49.6%(65/131)比7.6%(10/131)]、p53阳性表达率[60.3%(79/131)比13.0%(17/131)]、HER2阳性表达率[79.4%(104/131)比16.8%(22/131)]均高于癌旁组织(均P<0.001)。131例患者随访3年无失访者,随访率为100%;随访3年内复发15例(11.5%),转移8例(6.1%),死亡10例(7.6%),预后不良发生率为25.2%(33/131),其余98例(74.8%)预后良好。预后不良组TNM分期Ⅲ期、有淋巴结转移、组织低分化、肿瘤长径≥3 cm及survivin阳性、p53阳性、HER2阳性患者比例均高于预后良好组(均P<0.05)。多因素logistic回归分析显示,TNM分期Ⅲ期[OR=5.323(95%CI 2.190~12.936)]、有淋巴结转移[OR=4.773(95%CI 1.964~11.600)]、肿瘤长径≥3 cm[OR=3.582(95%CI 1.474~8.706)]及癌组织survivin阳性[OR=2.740(95%CI 1.127~6.659)]、p53阳性[OR=3.271(95%CI 1.346~7.949)]、HER2阳性[OR=3.873(95%CI 1.594~9.412)]为乳腺癌患者预后的独立危险因素(均P<0.001)。ROC曲线分析显示,以survivin、p53、HER2阳性及两两联合判断乳腺癌患者预后不良的曲线下面积均>0.80(均P<0.001),三者联合的曲线下面积为0.944(95%CI 0.890~0.977)(P<0.001)。结论survivin、p53、HER2在乳腺癌组织中表达均较高,三者的表达情况可用于判断乳腺癌患者预后,且三者联合的判断价值更高。

Objective To investigate the expressions of apoptosis-related factors survivin,p53 and human epidermal growth factor receptor 2(HER2)in breast cancer tissues and their prognostic value.Methods A total of 131 patients undergoing radical mastectomy for breast cancer who were admitted to Tangshan Maternal and Child Health Care Hospital from February 2015 to January 2019 were selected as the research subjects.During the operation,the cancer tissues and adjacent tissues(normal tissues>3 cm from the tumor margin)were collected from the patients.Expressions of survivin,p53 and HER2 in cancer tissues and adjacent tissues of patients were detected by using immunohistochemistry.The prognoses of patients were recorded after the follow-up for 3 years;the recurrence,metastasis and death treated as the poor prognosis,the rest prognoses of patients were treated as the good prognosis group.The difference of clinicopathological characteristics between the poor prognosis group and the good prognosis group was compared.Multivariate logistic regression was used to analyze risk factors for prognosis of breast cancer patients.The result of prognosis of breast cancer was taken as the golden standard.The receiver operating characteristic(ROC)curve was used to analyze the value of survivin pasitive,p53 pasitive,HER2 pasitive alone,the combination of both and the combination of the there in the judgement of poor prognosis of breast cancer.Results The positive expression rates of survivin[49.6%(65/131)vs.7.6%(10/131)],p53[60.3%(79/131)vs.13.0%(17/131)]and HER2[79.4%(104/131)vs.16.8%(22/131)]in cancer tissues were higher than those in adjacent tissues(all P<0.001).A total of 131 breast cancer patients were followed up for 3 years without any loss of follow-up,and the follow-up rate was 100%.Within the follow-up for 3 years,there were 15(11.5%)cases of recurrence,8(6.1%)cases of metastasis,and 10(7.6%)cases of death,the incidence of poor prognosis was 25.2%(33/131);and the remaining 98 cases had good prognosis.The proportions of patients with TNM stageⅢ,lymph node metastasis,poorly differentiated histology,tumor diameter≥3 cm,survivin,p53,and HER2 positive expressions in the poor prognosis group were higher than those in the good prognosis group(all P<0.05).Multivariate logistic regression analysis showed that TNM stageⅢ[OR=5.323(95%CI 2.190-12.936)],lymph node metastasis[OR=4.773(95%CI 1.964-11.600)],tumor diameter≥3 cm[OR=3.582(95%CI 1.474-8.706)],positive survivin[OR=2.740(95%CI 1.127-6.659)],positive p53[OR=3.271(95%CI 1.346-7.949)],and positive HER2[OR=3.873(95%CI 1.594-9.412)]were independent risk factors for prognosis of breast cancer(all P<0.001).The ROC curve results showed that the area under the curve(AUC)values of survivin positive,p53 positive,HER2 positive,and the combination of any two were more than 0.80(all P<0.001);the AUC of the combination of the three was 0.944(95%CI 0.890-0.977)(P<0.001).Conclusions The expressions of survivin,p53,and HER2 are highly expressed in breast cancer tissues.The expressions of the three can be used to judge the prognosis of breast cancer patients,and the combination of the three has a higher judgement value.