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

DOI 機関リポジトリ
  • 堀口 慎一郎
    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
  • Hishima Tsunekazu
    Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • Hayashi Yukiko
    Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • Shiozawa Yumiko
    Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • Horiguchi Kazumi
    Department of Surgery, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • Kuroi Katsumasa
    Department of Surgery, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • Toi Masakazu
    Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Funata Nobuaki
    Department of Pathology, Cancer and Infectious Diseases Center of Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • 江石 義信
    Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan

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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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