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

HER2 oncoprotein plays an essential role inbreast cancer growth and differentiation.Determination of HER2 status contributes not onlyto predicting survival but also to selecting thepatients for anti-HER2 therapy. HER2 proteinexpressed in human cancer cells often containsvariant forms as well as the full-length wild-typeform. In the present study, we investigated thesubcellular localization of HER2 protein in 1053primary breast cancer tissues. HER2 protein wasstained by various immunohistochemical methodsand studied by immunoelectron microscopy toconfirm the intracellular localization.Thirty-four of 1053 specimens showed cytoplasmicstaining of the intracellular domain of HER2protein by the HercepTest® and CB-11. In contrast,no immunoreactivity to the antibodiesagainst the extracellular domain was observed.None of the 34 specimens showed amplification ofthe HER2 protein by fluorescence in situ hybridization.Subsequently, we studied the associationof the cytoplasmic expression of HER2 with neuroendocrinedifferentiation. Interestingly, all 34specimens had some positive signals of neuroendocrinemarkers such as synaptophysin, chromogranin A, neuron-specific enolase, and CD56.Although the result is preliminary, it warrants furtherstudy on the role of the cytoplasmic variantform of HER2 in breast cancer growth, particularlyin the aspect of neuroendocrine differentiation.