HER-2/neu cytoplasmic staining is correlated with neuroendocrine differentiation in breast carcinoma

Shin-ichiro Horiguchi; Tsunekazu Hishima; Yukiko Hayashi; Yumiko Shiozawa; Kazumi Horiguchi; Katsumasa Kuroi; Masakazu Toi; Nobuaki Funata; Yoshinobu Eishi

doi:10.11480/jmds.570205

Shin-ichiro Horiguchi , Tsunekazu Hishima, Yukiko Hayashi, Yumiko Shiozawa, Kazumi Horiguchi, Katsumasa Kuroi, Masakazu Toi, Nobuaki Funata, Yoshinobu Eishi

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Shin-ichiro Horiguchi Corresponding author
Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Tsunekazu Hishima
Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Yukiko Hayashi
Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Yumiko Shiozawa
Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Kazumi Horiguchi
Department of Surgery, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Katsumasa Kuroi
Department of Surgery, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Masakazu Toi
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Nobuaki Funata
Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
Yoshinobu Eishi
Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan

Keywords: HER2/neu, cytoplasmic staining, neuroendocrine differentiation, breast cancer, immunohistochemistry

JOURNAL OPEN ACCESS

2010 Volume 57 Issue 2 Pages 155-163

DOI https://doi.org/10.11480/jmds.570205

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Abstract

HER2 oncoprotein plays an essential role in breast cancer growth and differentiation. Determination of HER2 status contributes not only to predicting survival but also to selecting the patients for anti-HER2 therapy. HER2 protein expressed in human cancer cells often contains variant forms as well as the full-length wild-type form. In the present study, we investigated the subcellular localization of HER2 protein in 1053 primary breast cancer tissues. HER2 protein was stained by various immunohistochemical methods and studied by immunoelectron microscopy to confirm the intracellular localization. Thirty-four of 1053 specimens showed cytoplasmic staining of the intracellular domain of HER2 protein by the HercepTest® and CB-11. In contrast, no immunoreactivity to the antibodies against the extracellular domain was observed. None of the 34 specimens showed amplification of the HER2 protein by fluorescence in situ hybridization. Subsequently, we studied the association of the cytoplasmic expression of HER2 with neuroendocrine differentiation. Interestingly, all 34 specimens had some positive signals of neuroendocrine markers such as synaptophysin, chromogranin A, neuron-specific enolase, and CD56. Although the result is preliminary, it warrants further study on the role of the cytoplasmic variant form of HER2 in breast cancer growth, particularly in the aspect of neuroendocrine differentiation.

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