PURPOSETo study retrospectively the long-term prognostic significance of HER-2 oncoprotein expression in breast cancer (BC).PATIENTS AND METHODSTwo hundred nine consecutive female patients with inv...

Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up.

Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease.

The human erbB-2 oncogene encodes a tyrosine kinase receptor. A ligand for the erbB-2 receptor (gp30), with an apparent molecular weight of 30,000, was reported to modulate the growth of cells overexpressing erbB-2. Whereas low concentrations of gp30 induced proliferation of these cells, higher concentrations inhibited their growth. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells AU-565 and MDA-MB-453 (which overexpress erbB-2) and MCF-7 cells (which express low levels of this protooncogene). Ligand concentrations that inhibited growth in cells overexpressing erbB-2 induced apparent differentiation of cells with a more mature phenotype, i.e., with characteristics such as inhibited cell growth, altered cytoplasmic and nuclear morphology, and increased synthesis of milk components (casein and lipids). No significant effect of the ligand was observed in the human breast cancer cell line MCF-7. Concomitant with the induction of differentiation in AU-565 and MDA-MB-453 cells, the erbB-2 protein was translocated from membrane to the cytoplasm and perinuclear sites. These findings indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is associated with an apparent induction of differentiation.

http://cgd.aacrjournals.org/cgi/reprint/3/7/401.pdf

A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells

Breast cancer heterogeneity: Evaluation of clonality in primary and metastatic lesions

erbB-2 antisense oligonucleotides inhibit theproliferation ofbreast carcinoma cells witherbB-2 oncogeneamplification

This study was performed to evaluate the correlation between HER-2/neu gene expression and DNA ploidy patterns. Forty-five cases of breast-cancer were analyzed. Immunohistochemical staining of HER-2/neu protein on frozen sections was used to detect the HER-2/neu protein, and the Feulgen DNA staining method was used to assess DNA amounts in the same tumor cells. Positive HER-2/neu overexpression was evaluated visually, and quantitation of the HER-2/neu protein was measured by image analysis. Twenty-two of the 45 cases were visually scored to be positive for the overexpression of the HER-2/neu protein, and these cases also contained above 10% HER-2/neu protein compared with a standard control cell line. All 22 of these cases had near-tetraploid DNA content. In contrast, cells, derived from the 23 cases that did not overexpress the HER-2/neu protein, contained DNA amounts that ranged from euploid (diploid) to varying degrees of aneuploid. The results of this study indicated that tumors that overexpress the HER-2/neu protein have tetraploid or near-tetraploid DNA content. This pattern could relate to the biological behavior of these tumors.

HER-2/neu oncogene expression and DNA ploidy analysis in breast cancer.

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HER-2/neu oncogene expression and DNA ploidy analysis in breast cancer.