HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

G E Konecny, L Santos, B Winterhoff, M Hatmal, G L Keeney, A Mariani, M Jones, C Neuper, B Thomas, L Muderspach, D Riehle, H-J Wang, S Dowdy, K C Podratz, M F Press, G E Konecny, L Santos, B Winterhoff, M Hatmal, G L Keeney, A Mariani, M Jones, C Neuper, B Thomas, L Muderspach, D Riehle, H-J Wang, S Dowdy, K C Podratz, M F Press

Abstract

Type II endometrial cancers (uterine serous papillary and clear cell histologies) represent rare but highly aggressive variants of endometrial cancer (EC). HER2 and EGFR may be differentially expressed in type II EC. Here, we evaluate the clinical role of HER2 and EGFR in a large cohort of surgically staged patients with type II (nonendometrioid) EC and compare the findings with those seen in a representative cohort of type I (endometrioid) EC. In this study HER2 gene amplification was studied by fluorescence in situ hybridisation (FISH) and EGFR expression by immunohistochemistry. Tissue microarrays were constructed from 279 patients with EC (145 patients with type I and 134 patients with type II EC). All patients were completely surgically staged and long-term clinical follow up was available for 258 patients. The rate of HER2 gene amplification was significantly higher in type II EC compared with type I EC (17 vs 1%, P<0.001). HER2 gene amplification was detected in 17 and 16% of the cases with uterine serous papillary and clear cell type histology, respectively. In contrast, EGFR expression was significantly lower in type II compared with type I EC (34 vs 46%, P=0.041). EGFR expression but not HER2 gene amplification was significantly associated with poor overall survival in patients with type II EC, (EGFR, median survival 20 vs 33 months, P=0.028; HER2, median survival 18 vs 29 months, P=0.113) and EGFR expression retained prognostic independence when adjusting for histology, stage, grade, and age (EGFR, P=0.0197; HER2, P=0.7855). We conclude that assessment of HER2 gene amplification and/or EGFR expression may help to select type II EC patients who could benefit from therapeutic strategies targeting both HER2 and EGFR.

Figures

Figure 1
Figure 1
(A) Kaplan–Meier survival plots of all type I and type II endometrial cancer patients with available clinical follow-up information (n=258) according to the histology type and (B) Kaplan–Meier survival plots among type II endometrial cancer patients with available follow up (n=133) according to FIGO stage.
Figure 2
Figure 2
Kaplan–Meier survival plots of all type I and type II endometrial cancer patients with available clinical follow-up information (n=258) according to HER2 status (A), and EGFR status (B).
Figure 3
Figure 3
Kaplan–Meier survival plots of all type II endometrial cancer patients with available clinical follow-up information (n=133) according to HER2 status (A), and EGFR status (B).

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