This small but extensively studied group of cases has indicated that increased c-erbB-2 protein can be identified routinely in fixed tissue sections, making it possible to carry out extensive studies to look for clinical correlates, but also to assess the stage in tumour progression at which the increased expression occurs and whether it correlates with any potentially premalignant condition.
In order to examine the role of the erbB-2 oncogene in human breast cancer, gene amplification and expression were examined in multiple stages of tumor progression.
Inappropriate expression of Her-2/neu (ERBB2) gene has been associated with impaired breast cancer prognosis, suggesting a functional role in tumor progression.
Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis.
Our results suggest that dysfunction of the TP53 protein is associated with tumor progression, as we found an association between TP53 abnormalities and accumulation of genetic lesions, measured as overall allelic imbalance (AI), homogeneously staining regions (HSR) and strong ERBB2 overexpression.
We realized that these studies did not rule out differences in the mechanism of cancer progression which might show themselves by a different association between p53 and c-erbB2 expression and stage in the two populations.
In different types of human cancer there is an overexpression of the c-erbB-2 (HER2/neu) oncogene, which is thought to be involved in tumor progression.
Two closely related receptors, the epidermal growth factor receptor (EGFR) and ErbB2, are overexpressed in a significant percentage of breast and prostate carcinomas, among others, with this up-regulated signaling correlating with tumor progression.
Although heparanase activity seems to play an essential role in tumor progression, expression of oncogenes, such as erbB2 and Mdm2 seems to play the dominant role in the development of ovarian cancer.
We conclude that c-erbB2 is a marker of tumour progression in NSCLC which can be observed on protein level and reflects chromosomal alterations at 17q21.
Although expression of the HER-2/neu oncogene has been correlated with tumor progression in prostate cancer, the biologic significance of detecting HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) or evidence for protein overexpression by immunohistochemistry (IHC) remains unclear.
We conclude that c-erbB-2 is related with tumor progression in CRC which can be observed on protein level and reflects chromosomal gain at the locus at 17q.
G3BP was also overexpressed in human breast tumors in parallel with HER2 overexpression and in an estrogen-independent manner, suggesting a role for G3BP in cancer progression.
Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%).
These data suggest that 1) overexpression of HER2 in nontumorigenic mammary epithelial is permissive for the ability of TGF-beta to induce cell motility and Rac1 activity, and 2) HER2 and TGF-beta signaling cooperate in the induction of cellular events associated with tumor progression.
By univariate analysis, TOP2alpha index (p=0.0267), HER2 score (p =0.028) and p53 index (p=0.0188) were significantly and loss of TOP2alpha gene (p=0.0575) tendentially correlated with tumor recurrence, while loss of HER2 gene (p=0.069) and loss of p53 gene (p=0.0587) were tendentially correlated with tumor progression.
To evaluate EGFR and HER2 copy number changes and to assess their significance to tumor progression in a large group of patients with larynx cancer through the construction of a tissue microarray (TMA) consisting of 1,385 biopsies.