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乳腺癌组织P16基因异常表达及意义

he aberrant expression and implication of P16 in breast cancers

中文摘要英文摘要

目的 通过分析浸润性导管癌组织中P16异常表达确定与其它分子标志及临床病理特征之间的关系及意义。方法 收集手术切除浸润性导管癌标本72例,免疫组织化学检测P16、Her-2、ER、PR、P53、Ki-67表达,分析各项免疫组化指标、以及临床病理特征(绝经、肿瘤大小、组织学分级、淋巴结转移)的关系。 结果 36.1%(26/72例)浸润性导管癌组织中P16异常表达。随着表达水平的增高不仅P16阳性着色细胞增多,并且其分布发生变化:从部分细胞散在阳性时的胞核着色(1+),发展为弥漫强阳性着色时则为胞核与胞浆的同时着色(或失去胞核着色),甚至胞外也可出现着色(3+)。并且P16异常表达多集中于ER阴性患者(78.6%),远高于ER阳性组(9.1%)(p<0.001)。同时,Ki-67高指数也多分布于P16 阳性组(p=0.003)。而在高分化、中分化和低分化三组中,P16表达的阳性率也随之增高:11.8%、27.6%、61.5%,差异显著(p=0.002)。而绝经前患者P16表达的阳性率(55.6%)显著高于绝经后(24.4%)(p=0.008)。结论 乳腺癌中P16异常表达与雌激素受体表达缺失相关,与Ki-67指数呈正相关,并多发生于绝经前患者、组织学分级高肿瘤。提示P16异常表达可能内分泌治疗反应差,以及侵袭性强的乳腺癌。

Objective To evaluate the relationship between the aberrant expression of P16 and the clinic-pathological features in breast cancer. Methods 72 cases of breast cancer were collected and the expression of P16, Her-2, ER, PR, P53, Ki-67 was measured by immunohistochemistry. Their correlations with the clinic-pathological features(menstruation, tumor size, histological grade, lymph node metastasis were statistically analyzed. Results Abnormal expression of P16 was detected in 36.1%(26/72 case)of breast cancers. The staining of P16 was not only increased,but also the subcellular distribution was changed from nuclear to cytoplasmic or whole cell staining. In general, the individual cell staining (1+) usually presented nuclear, while as increasing expression, P16 showed mainly in cytoplasmic or whole cells( 3+) even diffusing in extracellular, and the moderate staining was multi-focal both in nuclear and cytoplasmic. The expression of P16 was significantly increased in ER negative group compared with ER positive group (78.6% vs 9.1%)(p<0.001). Statistical analysis showed a significant correlation of high Ki67 index with the group of P16 positive (U=314.500, Degree freedom=2, p=0.003). In addition, significant difference was calculated between pre- and post- menopause (55.6% vs 24.4%, p=0.008)and P16 expression were also more credited to the poor-differentiated group in histological grading: 11.8% for high differentiated, 27.6% for moderated and 61.5% for poor group, respectively(p=0.002). Conclusions The aberrant expression of P16 in breast cancers correlated closely with loss of estrogen receptor, high proliferation index or high histologic grade, predisposed to the patients of premenopause, implicating that the abnormal expression of P16 should be a predictor of poor response to endocrine therapy or more aggressive behavior.

崔素萍、王花丽、彭伟、张波、侯琳、刘海静

肿瘤学基础医学临床医学

乳腺癌P16ERKi-67

Breast cancerP16ERKi67

崔素萍,王花丽,彭伟,张波,侯琳,刘海静.乳腺癌组织P16基因异常表达及意义[EB/OL].(2012-01-19)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201201-717.点此复制

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