Her2/neu expression in cancer: the pathologist as diagnostician or prophet?

Following its identification, much of the original work on HER2/neu was performed on the breast where this gene is amplified and/or overexpressed in 20% to 30% of carcinomas.4,5 In all of the cancers, HER2/neu gene-expression is usually associated with tumor aggressiveness and poor prognosis.7,8 In breast cancer, several studies identified the value of analysing HER2/neu as an approach to predicting the response of individual tumours to chemotherapy as well as in the use of recombinant humanized antibodies to the HER2/neu protein in the active management of patients with metastatic breast disease.9 Despite all of these studies, and the wide experience of this oncogene in epithelial neoplasia, the role of HER2/neu gene activation and protein expression in soft tissue tumors remains so poorly understood that robust molecular data supporting immunohistochemical studies in these tumours are scarce. The various transcripts appear to differ by a variety of mutations including truncation of the N-terminus, truncation of the C-terminus, presence or absence of 4 cassette exons as well as common exons with different boundaries since an internal intron is not always spliced out. [...]irrespective of the structural integrity of this gene, its expression in any given cell system is potentially highly variable and significantly altering the phenotype properties of the cells in which each different gene product becomes expressed.