【摘要】 目的 探讨p16表达在胃癌前病变、早期胃癌及癌旁非肿瘤性胃黏膜中的表达及临床意义。方法 使用内镜黏膜下剥离术(ESD)获得的早期胃癌标本30例(除黏膜内癌，还包括低级别异型增生21例、高级别异型增生23例、黏膜下浸润癌9例),采用免疫组织化学法检测p16、Ki-67、MUC5AC、MUC6、MUC2表达，分析标志物之间，以及与癌分化、临床特征的关系。结果 p16在非肿瘤性胃黏膜组织中呈阴性或个别细胞核表达(≤1+),而低级别异型增生、高级别异型增生、黏膜内癌及黏膜下浸润癌细胞中其过表达(≥2+)阳性率分别为4.8%、39.1%、80.0%、88.9%,差异均具有统计学意义(χ~2=34.515,P<0.001)。p16表达方式分析显示8例低级别异型增生中均为核阳性，而15例高级别异型增生阳性中，2例为核/质阳性(2/15,13.3%),28例黏膜内癌阳性中，22例为核/质阳性(22/28,78.6%),9例黏膜下浸润癌8例为核/质阳性(8/9,88.9%)。p16核/质阳性在黏膜内癌及黏膜下浸润癌与高级别异型增生间具有显著性差异(χ~2=16.856,P<0.001;χ~2=10.286,P=0.001)。p16表达与Ki-67指数在低级别异型增生、高级别异型增生、黏膜内癌相关，但浸润癌中p16过表达高而Ki-67指数较低(22.2%)。p16过表达与癌分化程度、细胞类型，以及其他临床特征无关。但同一样本的不同区域p16表达在高级别异型增生及早癌中有一定的异质性，在检测中需要注意。结论 p16过表达存在于胃癌前病变及早期胃癌，与良性增生有鉴别意义；尤其p16核/质过表达对于高级别异型增生、黏膜内癌、浸润癌具有提示意义；同时，在胃癌前病变及早期胃癌p16表达与Ki-67增殖指数具有一致性。更多还原

【Abstract】 Objective To evaluate the significance of expression p16 in gastric precancerous and cancerous lesions. Methods ESD samples from 30 cases of early gastric cancer, with comprising of low grade dysplasia(LGD) in 21 cases, high grade dysplasia(HGD) in 23 cases, and submucosal invasive carcinoma in 9 cases, were collected. The expression of p16, Ki67, MUC5 AC, MUC6 and MUC2 was stained by immunohistochemistry, and correlations of their expression and cancer differentiation, clinicopathological features were statistically analyzed. Results The expression of p16 in non-neoplastic or intestinal metaplasia was negative or only nuclear positive in occasional cells(≤ 1+), while over-expression of p16(≥ 2+) increased markedly from LGD(4.8%), HGD(39.1%), to intramucosal carcinoma(80.0%) and submucosal invasive carcinoma(88.9%), with statistical significances(χ~2= 34.515,P<0.001). In addition, the analysis on subcellular expression of p16 showed that all of LGD was nuclear positive, while the nuclear/cytoplasmic positive was in 2 of 15 cases of HGD(13.3%), 22 of 28 cases of intramucosal carcinoma(78.6%), 8 of 9 cases of submucosal invasive carcinoma(88.9%), respectively, with statistical differences between HGD and intramucosal or submucosal invasive carcinoma(χ~2=16.856, P<0.001;χ~2=10.286, P=0.001). Moreover, the expression of p16 positively correlated with Ki67 proliferation index in LGD, HGD and intramucosal carcinoma, but in contrary, over-expression of p16 was more frequently detected in submucosal invasive components, in which Ki67 was generally low. Over-expression of p16 was not correlated with either cancer differentiation, cell types or other clinicopathological features. It was worth to mention that expression of p16 could present some heterogeneous in different sampling from same specimen. Conclusion Over-expression of p16 is frequently found in gastric precancerous or cancerous lesions, differing from non-neoplastic hyperplasia, and especially nuclear/cytoplasmic expression of p16 is more credited to HGD, intramucosal carcinoma and submucosal invasive components. Meanwhile, there is a correlation between the expression of p16 and Ki67 index in these gastric lesions.更多还原