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Ancillary p16INK4a adds no meaningful value to the performance of ER/PR/Vim/CEA panel in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray study
Authors:Chung-Chin Yao  Lai-Fong Kok  Ming-Yung Lee  Po-Hui Wang  Tina S. Wu  Yeu-Sheng Tyan  Ya-Wen Cheng  Mei-Fen Kung  Chih-Ping Han
Affiliation:(1) Department of Surgery, Chung-Shan Medical University Hospital, Taichung, Taiwan;(2) Department of Pathology, China Medical University Hospital, Taichung, Taiwan;(3) Clinical Trial Center, Chung-Shan Medical University Hospital, Taichung, Taiwan;(4) Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Taichung, Taiwan;(5) David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA;(6) Department of Medical Imaging, Chung-Shan Medical University Hospital, Taichung, Taiwan;(7) Department of Medical Imaging and Radiological Science, Chung-Shan Medical University, Taichung, Taiwan;(8) Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan;(9) Statistical Team, Division of Clinical Science, Center for Drug Evaluation, Taipei, Taiwan
Abstract:Purpose  Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) are uterine malignancies that have differing biological behavior. The choice of appropriate therapeutic plan depends indeed on the tumor’s site of origin. In this study, we not only compare the individual expression status of five immunomarkers (ER, PR, Vim, CEA, and p16INK4a), but also evaluate whether p16INK4a adds value to the ER/PR/Vim/CEA panel characteristics in distinguishing between primary ECA and EMA. Methods  A tissue microarray (TMA) was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. TMA sections were immunostained with five anti-bodies, by avidin–biotin complex (ABC) method for antigen visualization. The staining intensity and area extent of the immunohistochemical (IHC) reactions were appraised by using the semi-quantitative scoring system. Results  The four respective markers (ER, PR, Vim, CEA) and their combined panel expressions showed significant (p < 0.05) frequency differences between ECA and EMA tumors. The p16INK4a marker also revealed a significant frequency difference (p < 0.05) between the two sites of origin, but did not demonstrate to have any supplementary value to the 4-marker panel. Conclusion  According to our data, when there is histomorphological and clinical doubt as to the primary site of origin, we recommend that the conventional 4-marker (ER/PR/Vim/CEA) panel is appropriate. Ancillary p16INK4a-marker testing does not add value to the 4-marker panel in distinguishing between primary ECA and EMA. C.-C. Yao and L.-F. Kok have equally contributed to this article.
Keywords:Endocervical adenocarcinomas  Endometrial adenocarcinomas  Endocervical  Endometrial  Tissue microarray  Immunohistochemistry  Estrogen receptor  Progesterone receptor  Vimentin  Carcinoembryonic antigen  p16INK4a   Hematoxylin and eosin  Negative predictive value  Positive predictive value
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