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. 2008 Jan;108(1):3-9.
doi: 10.1016/j.ygyno.2007.09.007. Epub 2007 Oct 18.

An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study

T A Grushko  1 , V L Filiaci, A J Mundt, K Ridderstråle, O I Olopade, G F Fleming; Gynecologic Oncology Group
Affiliations

An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study

T A Grushko et al. Gynecol Oncol. 2008 Jan.

Abstract

Objectives: To investigate the frequency and potential prognostic or predictive value of HER-2 amplification or overexpression in advanced and recurrent endometrial cancers.

Methods: Immunohistochemical staining (IHC; DAKO Herceptest) and fluorescence in situ hybridization (FISH; Vysis Inc. PathVysion DNA Probe Kit) were performed on specimens collected on a randomized Gynecologic Oncology Group (GOG) protocol testing the addition of paclitaxel to doxorubicin/cisplatin.

Results: HER-2 overexpression (either 2+ (moderate) or 3+ (strong) immunostaining) and HER-2 gene amplification (a ratio of HER-2 copies to chromosome 17 (CEP17) copies > or = 2) were detected in 44% (104 of 234; 58 were 2+ and 46 were 3+) and 12% (21 of 182) of specimens, respectively. There was a significant increased frequency of overexpression in serous tumors vs. all others (23 of 38, 61% vs. 81 of 196, 41%, respectively, P=0.03). HER-2 amplification also appeared to be more common in serous tumors, but results were not significant (6 of 28, 21% vs. 15 of 141, 11%, P=0.12). There was a significant association between grade and HER-2 amplification among nonserous tumors, with grades 1, 2, and 3 cancers demonstrating 3%, 2%, and 21% amplification, respectively (P=0.003). Neither overexpression nor amplification predicted overall survival (OS) after adjusting for treatment and performance status.

Conclusions: HER-2 amplification was more common in high grade tumors with a trend to being more common in serous tumors. There was no clear evidence for a survival difference or a difference in benefit from the addition of paclitaxel for women with HER-2 amplified or overexpressed tumors; however, power to detect clinically meaningful differences was low.

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Figures

Figure 1
Figure 1
Representative photomicrographs of adjacent tissue sections from different cell types of advanced endometrial carcinomas after HER-2 IHC (A–D) and FISH (E–H). The HER-2 gene is localized by red fluorescent signals, and the chromosome 17 centromere (CEP17) is localized by green fluorescent signals. The cells were counterstained with DAPI (4′,6-diamidino-2-phenilindole (blue). Original magnification × 1200. A, E, endometrial carcinoma of mixed histology displaying the high level of protein expression (3+) and high level of gene amplification (mean HER-2/cell =28.6; mean CEP17/cell = 2.5; ratio = 11.3). 52% of cells were polysomic for chromosome 17. B, F, USC, exhibiting strong 3+ membranous staining of HER-2 and moderate levels of HER-2 amplification (mean HER-2/cell =5.7; mean CEP17/cell = 1.8; ratio = 3.24). 40% of cells were monosomic and 12% of cells were polysomic for chromosome 17. C, G, Example of endometrial carcinoma of endometrioid histology, which was moderately positive for HER-2 expression (2+) but negative for HER-2 amplification (mean HER-2/cell =1.5; mean CEP17/cell = 2.4; ratio = 0.64). 34% of cells were polysomic for chromosome 17. D, H, endometrial carcinoma of endometrioid histology displaying no HER-2 protein expression (0) but high level of gene amplification (mean HER-2/cell =16.8; mean CEP17/cell = 1.6; ratio = 10.2). 55% of cells were polysomic for chromosome 17.
Figure 2
Figure 2
Survival curves A. survival by HER-2 IHC status B. survival by HER-2 FISH status C. survival by combined IHC and FISH status
Figure 2
Figure 2
Survival curves A. survival by HER-2 IHC status B. survival by HER-2 FISH status C. survival by combined IHC and FISH status
Figure 2
Figure 2
Survival curves A. survival by HER-2 IHC status B. survival by HER-2 FISH status C. survival by combined IHC and FISH status
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