乳腺癌组织P16异常表达的相关分析

Aberrant expression and correlative analysis of P16 in breast cancers

目的:分析浸润性导管癌组织中P16的异常表达及与其他分子标志和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,用免疫组织化学法检测P16、人表皮生长因子受体2(human epidermalgrowth receptor-2,Her-2)、雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、P53、Ki-67表达,分析P16与其他各项免疫组织化学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)浸润性导管癌组织中可检测到P16的异常表达,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,从部分细胞散在胞核着色(+),发展为弥漫强阳性着色,以及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(+++),并且P16异常表达多集中于ER阴性患者(78.6%,22/28),远高于ER阳性组(9.1%,4/44,P=0.000)。同时,Ki-67高指数也多分布于P16阳性组(P=0.003),在高分化、中分化和低分化3组中,P16异常表达的阳性率逐渐增高,分别为11.8%(2/17)、27.6%(8/29)、61.5%(16/26),差异具有统计学意义(P=0.002)。绝经前患者P16表达的阳性率(55.6%,15/27)显著高于绝经后(24.4%,11/45,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、肿瘤组织学分级高的患者;提示P16异常表达的患者可能内分泌治疗反应差,肿瘤具有高侵袭性。

Objective： To evaluate the relationship between the aberrant expression of P16 and the clinic-pathological features in breast cancers.Methods： In our study,72 cases of breast cancer were collected and the expressions of P16,Her-2（human epidermal growth receptor-2）,ER（estrogen receptor）,PR（progesterone receptor）,P53,Ki-67 were measured by immunohistochemistry.The correlations between the P16 and the clinic-pathological features（menstruation,tumor size,histological grade,lymph node metastasis）were statistically analyzed.Results： Aberrant expression of P16 was detected in 36.1%（26/72）of breast cancers.Not only was the staining of P16 increased,but also the subcellular localization was changed from nuclear to cytoplasm or whole cell staining.In general,the occasional cell staining（＋） usually presented in nuclear,as expression increased,P16 showed mainly in cytoplasm or whole cells（＋＋＋） even diffusive staining in extracellular,and the moderate staining was multi-focal both in nuclear and cytoplasm.The expression of P16 was significantly increased in ER negative group compared with ER positive group（78.6% vs.9.1%,P=0.000）.Statistical analysis showed a significant correlation of high Ki-67 index with the group of P16 positive（Z =-0.263,P=0.003）.In addition,significant difference was calculated between pre-and post-menopause（55.6% vs.24.4%,P=0.008）and P16 expressions were also more credited to the poor-differentiated group in histological gra-ding： 11.8%（2/17） for highly differentiated group,27.6%（8/29） for moderately differentiated group and 61.5%（16/26） for poorly differentiated group,respectively（P=0.002）.Conclusion： The aberrant expression of P16 in breast cancers correlated closely with loss of estrogen receptor,high proliferation index or high histological grade,predisposed to the patients of pre-menopause,implicating that the aberrant expression of P16 should be a predictor of poor response to endocrine therapy or more aggressive behavior.