Koo Chiew-Loon, Kok Lai-Fong, Lee Ming-Yung, Wu Tina S, Cheng Ya-Wen, Hsu Jeng-Dong, Ruan Alexandra, Chao Kuan-Chong, Han Chih-Ping
Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
J Transl Med. 2009 Apr 14;7:25. doi: 10.1186/1479-5876-7-25.
Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate 3 different scoring mechanisms of p16INK4a immunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs.
A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 24 EMAs. Tissue array sections were immunostained with a commercially available antibody of p16INK4a. Avidin-biotin complex (ABC) method was used for antigens visualization. The staining intensity and area extent of the IHC reactions was evaluated using the semi-quantitative scoring system. The 3 scoring methods were defined on the bases of the following: (1) independent cytoplasmic staining alone (Method C), (2) independent nucleic staining alone (Method N), and (3) mean of the sum of cytoplasmic score plus nucleic score (Method Mean of C plus N).
Of the 3 scoring mechanisms for p16INK4a expression, Method N and Method Mean of C plus N showed significant (p-values < 0.05), but Method C showed non-significant (p = 0.245) frequency differences between ECAs and EMAs. In addition, Method Mean of C plus N had the highest overall accuracy rate (81.6%) for diagnostic distinction among these 3 scoring methods.
According to the data characteristics and test effectiveness in this study, Method N and Method Mean of C plus N can significantly signal to distinguish between ECAs and EMAs; while Method C cannot do. Method Mean of C plus N is the most promising and favorable means among the three scoring mechanisms.
宫颈管腺癌（ECAs）和子宫内膜腺癌（EMAs）是影响子宫的恶性肿瘤；然而，它们的生物学行为有很大差异。这种差异具有临床意义，因为合适的治疗方法可能取决于肿瘤的起源部位。本研究的目的是评估p16INK4a免疫组织化学（IHC）染色的3种不同评分机制在区分原发性ECAs和EMAs方面的作用。
使用来自子宫切除标本的福尔马林固定、石蜡包埋组织构建组织微阵列（TMA），包括14例ECAs和24例EMAs。组织阵列切片用市售的p16INK4a抗体进行免疫染色。采用抗生物素蛋白-生物素复合物（ABC）法进行抗原可视化。使用半定量评分系统评估IHC反应的染色强度和面积范围。这3种评分方法基于以下定义：（1）仅独立的细胞质染色（方法C），（2）仅独立的细胞核染色（方法N），以及（3）细胞质评分与细胞核评分之和的平均值（方法C加N的平均值）。
在p16INK4a表达的3种评分机制中，方法N和方法C加N的平均值在ECAs和EMAs之间显示出显著的（p值<0.05）频率差异，但方法C显示无显著差异（p = 0.245）。此外，在这3种评分方法中，方法C加N的平均值在诊断区分方面具有最高的总体准确率（81.6%）。
根据本研究的数据特征和测试效果，方法N和方法C加N的平均值可以显著区分ECAs和EMAs；而方法C不能。方法C加N的平均值是这三种评分机制中最有前景和最有利的方法。
