These results suggest a role for the NEU gene product in the physiology of benign ovarian surface epithelium and the neoplastic epithelium of preinvasive borderline and some invasively malignant adenocarcinomas.
Amplification and/or overexpression of the erbB-2 gene have been demonstrated in 20-30% of adenocarcinomas of the breast, ovary, lung, and stomach and are associated with aggressive clinical course and poor prognosis.
These findings imply that a significant proportion of invasive mammary adenocarcinomas expressing c-erbB-2 protein is derived from ductal in situ carcinomas of the comedo type.
We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.
In marked contrast, c-erbB-2 proto-oncogene expression was found only in adenocarcinoma cells, and thus can be used as a marker for malignancy in diagnostic respiratory cytopathology.
It is also concluded that errors in the onco-suppressor gene p53, and especially in the external and internal domains of c-erbB2, which is also often expressed in Barrett's mucosa, may be implicated in the development of adenocarcinoma of the oesophagus.
Poorer survival rates and elevated recurrence rates following treatment have been shown in patients whose breast adenocarcinomas demonstrate increased c-erbB-2 expression.
In cervical adenocarcinomas, expression of c-myc was seen in 5 of 7 cases (71.6%), EGFR in all cases and c-erbB-2 in 2 of 7 cases (28.6%). c-myc immunoactivity was observed as nuclear or cytoplasmic stain or both, EGFR as membrane and cytoplasmic stain, c-erbB-2 as membrane stain.
Immunohistochemical staining of tumor tissue sections with p185 HER-2/neu antibodies demonstrated that only the 3 gastric adenocarcinomas with corresponding HER-2/neu gene amplification displayed membrane immunoreactivity.
Southern blot analysis of paired tumor and normal lung samples demonstrated that amplification of the c-erbB-2 gene is rare in NSCLC (2/60) and not restricted to adenocarcinomas.
Using avidin-biotin-peroxidase techniques and monoclonal antibody TA1, 313 archival primary adenocarcinomas of the breast were evaluated for c-erbB-2 overexpression; 290 of these were used for multiparametric statistical analysis.
Thus, the protein products of the amplified c-erbB-2 gene may have a role in the evolution of adenocarcinomas, as does the EGF receptor in some squamous-cell carcinomas.
The use of immunohistological staining to detect the level of expression of the c-erbB-2 protein in human breast adenocarcinomas may be of value in predicting tumour behaviour.