One hundred seventy-nine primary human gastric tumors not associated with early cancer or noncurative resection were examined immunohistochemically for the expression of c-erbB-2 protein.
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.
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.
These data suggest that 11p14 allelic loss plays a role in the evolution of human breast cancer, amplification of c-erbB-2 gene is associated with increasing stage of malignancy, and alteration of the c-myc gene in inflammatory breast carcinoma may contribute to the rapid progression of this human tumor subtype.
Southern blot analysis showed close similarity of the restriction patterns of the rat c-erbB-2 gene and the rat neu oncogene, suggesting possible involvement of c-erbB-2 in human cancer.
We previously reported that increased HER-2/neu expression led to more severe malignancy and increased metastatic potential in animal models and that the adenovirus 5 E1A gene repressed HER-2/neu gene expression at transcriptional level and was able to suppress tumor growth when stably transfected into human ovarian cancer SKOV-3 cells which overexpress HER-2/neu.
Overexpression of the c-erbB-2 proto-oncogene product (p185c-erbB-2) occurs frequently in different types of human cancer and is correlated with a significantly decreased survival in ovarian cancer patients.
Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy.
This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors.
The results of in situ hybridization using a 32P-labeled neu/erbB-2 RNA probe performed on four WHO grade I and II astrocytomas, seven WHO grade IV glioblastomas, one WHO grade II oligoastrocytoma, one WHO grade III anaplastic astrocytoma, and three WHO grade I meningiomas were consistent with these immunomorphological data, and Northern blot analysis also indicated an overexpression of neu/c-erbB-2 mRNA in gliomas of different grades of malignancy and in meningiomas.
This illustrates the complex nature of c-erbB-2 gene disregulation in cancer and suggests that multiple combinations of biological events and consequences are possible.
Based on the size exclusion S-200 column chromatography, we found only a single molecule containing c-erbB-2 oncoprotein activity in pooled sera from cancer patients whereas two oncoproteins slightly different in size were detected in breast tumor tissue cytosol.
Since we had previously shown that the adenovirus 5 E1A gene product can suppress transformation and metastatic properties induced by mutation-activated rat neu oncogene in mouse embryo fibroblast cells, we further examined whether E1A can abrogate malignancy in c-erbB-2/neu-overexpressing human ovarian cancer cells.
Amplification and overexpression of the erbB-2 gene in human tumors: its involvement in tumor development, significance as a prognostic factor, and potential as a target for cancer therapy.
The results show that c-erbB-2 expression in related to several histopathological features of malignancy and cell proliferation in breast cancer, but it has no independent prognostic value better than that of the established prognostic factors.