Cui Su-ping, Wang Hua-li, Peng Wei, Liu Hai-jing, Hou Lin, Zhang Bo
Department of Pathology, Peking University School of Basic Medical Science, Beijing, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2012 Oct 18;44(5):755-9.
To evaluate the relationship between the aberrant expression of P16 and the clinic-pathological features in breast cancers.
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.
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 grading: 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).
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.
评估P16异常表达与乳腺癌临床病理特征之间的关系。
本研究收集了72例乳腺癌病例，采用免疫组织化学法检测P16、HER-2（人表皮生长受体-2）、ER（雌激素受体）、PR（孕激素受体）、P53、Ki-67的表达。对P16与临床病理特征（月经、肿瘤大小、组织学分级、淋巴结转移）之间的相关性进行统计学分析。
72例乳腺癌中，36.1%（26/72）检测到P16异常表达。不仅P16染色增加，而且亚细胞定位从细胞核转变为细胞质或全细胞染色。一般来说，偶尔的细胞染色（+）通常出现在细胞核中，随着表达增加，P16主要出现在细胞质或全细胞中（+++），甚至在细胞外呈弥漫性染色，中等染色在细胞核和细胞质中均为多灶性。与ER阳性组相比，ER阴性组中P16的表达显著增加（78.6%对9.1%，P=0.000）。统计学分析显示，高Ki-67指数与P16阳性组显著相关（Z = -0.263，P=0.003）。此外，绝经前后差异有统计学意义（55.6%对24.4%，P=0.008），在组织学分级中，P16表达也更多见于低分化组：高分化组为11.8%（2/17），中分化组为27.6%（8/29），低分化组为61.5%（16/26），差异有统计学意义（P=0.002）。
乳腺癌中P16的异常表达与雌激素受体缺失、高增殖指数或高组织学分级密切相关，易发生于绝经前患者，这表明P16的异常表达可能是内分泌治疗反应不佳或行为更具侵袭性的一个预测指标。
