Amplification of the neu (or c-erbB-2 or HER) oncogene is found to be present in 15-30% of human breast carcinomas and has been reported to correlate with poor prognosis.
This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.
Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer.
Comparison of erbB-2 overexpression with clinical disease parameters revealed a correlation of this alteration with inflammatory mammary carcinoma (P = 0.042) implying an association of elevated erbB-2 protein levels with enhanced malignancy of the tumor cell in vivo.
Therefore, immuno-histological diagnosis with anti-c-erbB-2 antibody might be useful as an indicator to predict lymph-node involvement in breast cancer.
The c-myc gene was amplified 5-7-fold in two adenocarcinomas, the H-ras gene 3 5-fold in one adenocarcinoma, while the K-ras and the neu gene were amplified in lung metastases from a colorectal and a breast cancer primary respectively.
HER2 (or c-erbB-2), the human homolog of the rat neu proto-oncogene, encodes a transmembrane glycoprotein of the tyrosine kinase family that appears to play an important role in human breast carcinoma.
A similar analysis was performed for two other proto-oncogenes, c-erbB-2 and c-myc, also suspected of playing a role in the development of human breast cancer.
Some of these mutations involve amplification of protooncogenes (c-myc, c-erbB-2, and int-2) that have been shown to contribute to experimentally induced breast cancer in mouse model systems.
About 40% of breast carcinomas contain either amplified c-myc or c-erbB-2 protooncogenes, whereas simultaneous amplification of both was seen in only one sample, suggesting the involvement of two distinct molecular mechanisms in breast cancer.
Correlation of erbB-2 gene amplification with low levels of estrogen and/or progesterone receptors in primary breast cancer: do erbB-2 products delineate hormone-independent tumors?