Research

Scoring mechanisms of p16^INK4a immunohistochemistry based on either independent nucleic stain or mixed cytoplasmic with nucleic expression can significantly signal to distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study

Chiew-Loon Koo^1* , Lai-Fong Kok^2* , Ming-Yung Lee^3* , Tina S Wu⁴ , Ya-Wen Cheng⁵ , Jeng-Dong Hsu^1,6 , Alexandra Ruan⁷ , Kuan-Chong Chao⁸ and Chih-Ping Han^3,5,9

¹  Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC

²  Department of Pathology, China Medical University Hospital, Taichung, Taiwan, ROC

³  Clinical Trial Center, Chung-Shan Medical University Hospital, Taichung, Taiwan, ROC

⁴  David Geffen School of Medicine, University of California, Los Angeles. Los Angeles, California, USA

⁵  Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan, ROC

⁶  Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC

⁷  Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland, USA

⁸  Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, and Division of Obstetrics and Gynecology, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC

⁹  Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Taichung, Taiwan, ROC

author email corresponding author email* Contributed equally

Journal of Translational Medicine 2009, 7:25doi:10.1186/1479-5876-7-25

Published:	14 April 2009

Abstract

Background

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 p16^INK4a immunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs.

Methods

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 p16^INK4a. 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).

Results

Of the 3 scoring mechanisms for p16^INK4a 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.

Conclusion

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.