Human epidermal growth factor receptor-2 overexpression and amplification in metastatic and recurrent high grade or type 2 endometrial carcinomas

Rina Kato,¹ Kiyoshi Hasegawa,¹ Risa Ishii,¹ Akiko Owaki,¹ Yutaka Torii,¹ Shuko Oe,¹ Hiroshi Hirasawa,² Yoichi Kobayashi,³ Yasuhiro Udagawa<sup>1

1</sup>Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan; ²Department of Pathology, Fujita Health University School of Medicine, Toyoake, Japan; ³Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Japan

Introduction: Human epidermal growth factor receptor (HER)-2 overexpression or gene amplification is more common in high-grade or type 2 endometrial carcinomas. We assessed the discordance of HER-2 expression between primary and metastatic or recurrent endometrial carcinomas.
Materials and methods: Thirty-six primary, along with 14 metastatic and five recurrent tumors (matched to primaries), pathologically confirmed as high-grade or type 2 endometrial carcinomas, were submitted for immunohistochemistry (IHC) for HER-2. Fluorescence in situ hybridization was performed when the tumors showed HER-2 overexpression (≥2+ IHC score). The results of the IHC and fluorescence in situ hybridization assays were compared between the primary and metastatic or recurrent tumors. The relationships between HER-2 expression and clinicopathological factors or prognosis were investigated.
Results: HER-2 overexpression and HER-2 amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies ≥2.2) were detected in 33.3% (twelve of 36 patients) and 5.6% (two of 36 patients) of primary tumors, respectively. HER-2 overexpression was not associated with clinicopathological factors or prognosis. In 19 tumor specimens obtained from metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were detected in 57.9% (eleven patients) and 15.8% (three patients), respectively. HER-2 overexpression tended to predict a worse prognosis.
Conclusion: HER-2 expression in metastatic or recurrent tumors was more frequent than in matched primary high-grade or type 2 endometrial carcinomas. Trastuzumab in combination with cytotoxic chemotherapy may represent an alternative therapeutic option for these tumors.

Keywords: endometrial carcinoma, high grade, type 2, HER-2, metastatic or recurrent tumors