Diagnosis of metastatic breast cancer is associated with a very poor prognosis. New therapeutic targets are urgently needed, but their development is hampered by a lack of understanding of the mechanisms leading to tumor metastasis. Exemplifying this is the fact that the approximately 30% of all breast cancers overexpressing the receptor tyrosine kinase ErbB-2 are characterized by high metastat...

Overexpression of c-erbB-2 (also known as HER-2/neu) has been found in many human cancers, including head and neck squamous cell carcinoma (SCC). We therefore examined expression of the oncoprotein in oral SCC primary tumor samples and compared its relationship with clinical stages and survival rate. Out of 80 cases of oral SCC, high expression level (++ or +++) of c-erbB-2 was found in 41 case...

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. U...

Purpose: Breast cancer is the second leading cause of cancer mortality among women worldwide. The major problem with current treatments is tumor resistance, recurrence, and disease progression. ErbB-2–positive breast tumors are aggressive and frequently become resistant to trastuzumab or lapatinib. We showed previously that Notch-1 is required for trastuzumab resistance in ErbB-2–positive breas...

Amplification and overexpression of the c-erbB-2 oncogene are of prognostic significance in human breast cancer. Overexpression of c-erbB-2 is the result of gene amplification. However, increased transcript levels of c-erbB-2 are also detected in the absence of gene amplification. In this study for the detection of the overexpression mRNA in situ hybridisation (ISH) and immunohistochemistry (IH...

The prognostic role of c-erbB-2 in gastric cancer is controversial. We conducted a meta-analysis to evaluate the relationship between c-erbB-2 expression and the prognosis of gastric cancer. We evaluated 20 published studies assessing the relationship between c-erbB-2 and gastric cancer prognosis. The Revman 5.0 software was used to perform literature retrieval, article selection, data collecti...

6 Mechanisms of Resistance................................................... 9 6.1 Functional Redundancy Among ErbB Family Members...... 10 6.2 Role for Loss of Negative Regulators................................... 11 6.3 Accumulation of Soluble p95-ErbB-2................................... 11 6.4 Role for MUC4: Altered Receptor–Antibody Interaction .... 11 6.5 Crosstalk Between ErbB-2 and No...

PURPOSE Breast cancer is the second leading cause of cancer mortality among women worldwide. The major problem with current treatments is tumor resistance, recurrence, and disease progression. ErbB-2-positive breast tumors are aggressive and frequently become resistant to trastuzumab or lapatinib. We showed previously that Notch-1 is required for trastuzumab resistance in ErbB-2-positive breast...

The success of recent clinical trials using Herceptin (trastuzumab, a humanized anti–erbB-2 antibody) as therapy for patients with advanced breast cancer 1-3 has generated a great deal of renewed interest in laboratory testing for overex-pression of the erbB-2 oncoprotein. An article by Jacobs et al 4 in this issue of the Journal describes an interesting study evaluating interlaboratory agreeme...