The c-erbB-2 oncogene has been extensively studied in mammary carcinomas since Slamon and colleagues demonstrated the association between amplification and poor prognosis in 1987. Further work found that amplification was accompanied by overexpression of the protein; however, this relationship is not perfect. Recently, Hollywood and Hurst have shown increased transcription in some cell lines containing a single copy of the gene, causing mRNA accumulation in overexpressing cells. Protein expression appears to be a good indicator of various abnormalities in the c-ubB-2 gene. Fortunately, c-erbB-2 protein, unlike epidermal growth factor (EGF) receptor, survives most fixation procedures used in routine histopathology laboratories. This has enabled immunohistochemical studies to be carried out on archival material.
A higher incidence of c-erbB-2 positivity occurs in ductal carcinoma in situ ( X I S ) than in infiltrating carcinomas. In DCIS there is a very close association between protein expression and high grade (comedo type). This explains the very high incidence of c-erbB-2 positivity in Paget's disease of the nipple which is nearly always associated with high grade DCIS. A lower proportion of high grade infiltrating carcinomas express the protein, highlighting the difference in incidence of positivity in the two types of ductal lesion.
As well as having a potential role in the biological classification of mammary carcinomas, c-erbB-2 expression has been used to predict response to treatment. There have been reports that tumors expressing c-erbB-2 fail to respond to either chemotherapy or endocrine therapy. It is extremely difficult to conduct satisfactory trials to confirm these results since only a quarter of infiltrating mammary carcinomas are c-erbB-2-positive, and a very large number of stage-matched patients is necessary in order to achieve comparable treatment and control groups. However, two small studies carried out at Guy's Hospital have found that the presence of c-erbB-2 protein does not preclude a successful response to either adjuvant chemotherapy or endocrine therapy for metastatic disease. 0 1993 Wiley-Liss, inc.