Detection of HER2/neu receptor overexpression and/or amplification is a prerequisite for efficient anti-HER2 treatment of breast and gastric carcinomas.
Human epidermal growth factor receptor 2 (HER2/neu) gene amplification and HER2 protein overexpression have been associated with clinicopathological parameters and clinical outcome in many carcinomas.
No genes were up-regulated, and only a small number of genes were down-regulated both in cell lines and in carcinomas with high HER2/neu protein levels.
Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02).
Overexpression of the neu-protein, evidenced as membrane staining by immunohistochemistry, is detected in approximately 20% of invasive duct cell carcinomas, in approximately 50% of in situ duct cell carcinomas, and in almost 100% of cases of Paget's disease.
Immunohistochemical staining (IHC) of a total of 86 specimens (including 17 of those studied by ISH) localized NEU antigen expression to epithelial cells in 36 of 86 samples with strong membrane staining observed in 12, including 1 benign, 1 borderline serous carcinoma, 3 clear cell/endometrioid carcinomas, and 7 predominantly papillary serous carcinomas with areas of clear cell/endometrioid histology.
The neu receptor oncoprotein tyrosine kinase, capable of transforming cultured fibroblasts and causing mammary carcinomas in transgenic mice, carries a point mutation in its transmembrane domain and shows a constitutive tyrosine kinase activity.