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Assessing the Impact of Polysomy-17 on HER2 Status and the Correlations of HER2 Status With Prognostic Variables (ER, PR, p53, Ki-67) in Epithelial Ovarian Cancer: A Tissue Microarray Study Using Immunohistochemistry and Fluorescent In Situ Hybridization

Lin, Chih-Kuang M.D.; Lin, Wea-Lung D.D.S., M.S.; Chen, Fong-Lin M.D., Ph.D.; Lee, Ming-Yung Ph.D.; Kuo, Jang-Fang M.D.; Ruan, Alexandra; Tyan, Yeu-Sheng M.D., Ph.D; Chiang, Hung M.D.; Chou, Ming-Chih M.D., Ph.D.; Han, Chih-Ping M.D., Ph.D.

International Journal of Gynecological Pathology: July 2011 - Volume 30 - Issue 4 - p 372–379
doi: 10.1097/PGP.0b013e31820c9ff3
Pathology of the Upper Genital Tract: Original Articles

Although HER2 overexpression and Her2 amplification have been noted in breast and a variety of human cancers, we report here for the first time the impact of polysomy-17 on HER2 status and the correlations between HER2 status and other prognostic factors in patients with epithelial ovarian cancers (EOC).

We analyzed HER2, estrogen receptor (ER), progesterone receptor (PR), p53, and Ki-67 protein overexpressions by immunohistochemistry (IHC) and determined Her2 gene amplification by fluorescence in situ hybridization (FISH) in 27 tissue microarray samples from EOC patients.

We achieved 100% positive concordance (3/3) and 100% negative concordance (19/19) between HER2 testing by IHC and FISH. Both the total Her2 gene copies and FISH scores increased significantly in a stepwise order through the negative, equivocal, and positive HER2 IHC result categories in all 27 cases (P=0.001, P=0.001), and still increased significantly in 18 nonpolysomy-17 cases (P=0.007 and 0.013) after the exclusion of 9 polysomy-17 cases. HER2 protein expression is inversely correlated with both ER (P=0.002) and PR expressions (P=0.046). Her2 gene amplification is inversely correlated with ER expression (P=0.007) but not with PR expression (P=0.106).

This study showed extremely high positive and negative concordances between Her2 FISH and HER2 IHC assays. Polysomy-17 is insufficient for causing a significant impact on the relationship between HER2 testing by IHC and FISH in EOC. ER and PR expressions were inversely correlated with HER2 protein expression. In addition, ER but not PR expression is inversely correlated with Her2 gene amplification.

Institute of Medicine (C-K.L., M-C.C.)

Department of Pathology (W-L.L., J-F.K., C-P.H.)

Division of Pediatric Cardiology, Department of Pediatrics (F-L.C.), Chung Shan Medical University Hospital and School of Medicine, Chung Shan Medical University

Department of Internal Medicine (C-K.L.)

Department of Surgery (M-C.C.)

Department of Obstetrics and Gynecology (C-P.H.)

Clinical Trial Center (C-P.H.), Chung-Shan Medical University Hospital

Department of Statistics and Informatics Science (M-Y.L.), Providence University, Taichung

Taipei Institute Pathology (H.C.), Taipei, Taiwan

Krieger School of Arts and Sciences (A.R.), Johns Hopkins University, Baltimore, MD

Chih-Kuang Lin, Wea-Lung Lin, and Fong-Lin Chen equally contributed to this work.

Address correspondence reprint request to Chih-Ping Han, MD, PhD, Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital; Department of Pathology, School of Medicine, Chung-Shan Medical University, Taichung, Taiwan. e-mail: hanhaly@gmail.com

©2011International Society of Gynecological Pathologists