乳腺浸润性导管癌中生物钟基因NPAS2的表达及临床病理分析

Expression of circadian clock gene NPAS2 in invasive ductal carcinoma of breast and its correlation with the clinicopathological features

目的探讨生物钟基因NPAS2在乳腺浸润性导管癌中的表达,分析其与雌激素受体(ER)相关性等临床病理特征。方法采用免疫组织化学EnVision二步法对113例乳腺浸润性导管癌进行生物钟基因NPAS2及ER、孕激素受体(PR)、人表皮生长因子受体-2(HER2)、Ki-67表达检测。结果(1)113例乳腺浸润性导管癌标本,按半定量组织学评分标准分级,1级病例4例,2级50例,3级59例;(2)113例乳腺癌病例中,88例癌组织呈ER阳性,25例显示ER阴性;同时,32例乳腺癌标本存在HER2过表达,81例显示HER2阴性;(3)NPAS2在ER阴性病例的表达缺失率为20.00%(5/25),较ER阳性病例的表达缺失率4.54%(4/88)明显升高,差异有统计学意义(P<0.05);(4)NPAS2在32例HER2过表达病例的表达缺失率为18.75%(6/32),其余81例阴性病例的表达缺失率为3.70%(3/81),两组缺失差异有统计学意义(P<0.05);(5)免疫组化结果显示,NPAS2在正常乳腺导管上皮阳性表达,113例乳腺癌标本中有104例癌组织检测到NPAS2不同程度的阳性表达,9例呈阴性表达,表达缺失率为7.96%(9/113)。4例1级浸润性导管癌未见NPAS2表达缺失,2级浸润性导管癌的表达缺失率为2.00%(1/50),3级浸润性导管癌的表达缺失率为13.56%(8/59);(6)免疫组化染色方法检测肿瘤细胞ER表达,88例标本为ER阳性,25例为ER阴性。HER2基因免疫组化过表达病例共32例,免疫组化阴性表达病例81例;(7)NPAS2在肿瘤细胞中的表达与患者的ER状态和HER2基因有无过表达有关。结论生物钟基因NPAS2可能与乳腺浸润性导管癌的发生有关。NPAS2的表达缺失与乳腺浸润性导管癌组织ER阴性、HER2过表达存在高度相关性,可能与乳腺癌进展有关。

Objective To investigate the expression of circadian clock gene NPAS2(neuronal PAS domain protein 2)in invasive ductal carcinoma(IDC)of breast,and its correlations with estrogen receptor(ER)status,clinicopathological features.Methods Immunohistochemical EnVision method staining for NPAS2,ER,PR,HER2 and Ki-67 were performed in 113 cases of IDC.Results A total of 113 specimens of breast invasive ductal carcinoma were graded according to semi-quantitative histological scoring standards,with 4 cases of Grade 1,50 cases of Grade 2,and 59 cases of Grade 3.Eighty-eight of 113 breast cancer cases were ER positive,and 25 cases were ER negative.Meanwhile,32 breast cancer specimens had HER2 overexpression,and 81 cases showed HER2 negative.The expression loss rate of NPAS2 in ER negative cases was 20.00%(5/25)than that in ER positive cases(4.54%)(P<0.05).The expression loss rate of NPAS2 in 32 HER2 overexpression cases was 18.75%(6/32),which was significantly than that of negative cases(3.70%)(P<0.05).The results of immunohistochemistry showed that NPAS2 was in normal breast duct epithelium.Among 113 breast cancer specimens,104 cancer tissues had positive expression of NPAS2 to varying degrees,and 9 cases were negative.The expression loss rate was 7.96%(9/113).There was no loss of NPAS2 expression in 4 cases of Grade 1 IDC,the expression loss rate of Grade 2 IDC was 2.00%(1/50),and the expression loss rate of Grade 3 IDC was 13.56%(8/59).The expression of NPAS2 in tumor cells was correlated to the patients′ER status and whether there was overexpression of HER2 gene.Conclusion Circadian clock gene NPAS2 may be closely correlated to the tumorigenesis of IDC.Loss of NPAS2 expression is closely associated with ER status and overexpression of HER2 gene in IDC,and loss of NPAS2 expression may be associated with tumor progression of IDC.