title: HER-2/neu cytoplasmic staining is correlated with neuroendocrine differentiation in breast carcinoma.
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.
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. s.horiguchi@cick.jp
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Hishima
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Shiozawa
authors.forename: Kazumi
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kuroi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Funata
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D019002:CD56 Antigen / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000473:pathology; D002454:Cell Differentiation; D053379:Chromogranin A / Q000032:analysis; D004396:Coloring Agents; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D055099:Neuroendocrine Cells / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D016708:Synaptophysin / Q000032:analysis; D055815:Young Adult
chemical_list: D019002:CD56 Antigen; D053379:Chromogranin A; D004396:Coloring Agents; D010751:Phosphopyruvate Hydratase; D018719:Erb-b2 Receptor Tyrosine Kinases; D016708:Synaptophysin