Overexpression of HER2 Growth Factor Receptor Prognostic in Gastric Adenocarcinoma

Prognostic significance of p185HER2 overexpression in gastric adenocarcinoma and in vitro antiproliferative effect of p185HER2 monoclonal antibody (trastuzumab) in p185HER2 overexpressed Korean gastric cancer cells.

The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185HER2) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene amplified in various human cancers and associated with poor prognosis. Recombinant anti-p185HER2 monoclonal antibody trastuzumab targets cells that overexpress the p185HER2 protein and inhibits the growth of breast cancer cells expressing high levels of p185HER2, but questions remain regarding its use in other types of cancers.Researchers evaluated the relationship between p185HER2 overexpression, clinicopathological features, survival in 94 (M:F=52:42) gastric adenocarcinoma patients (median age : 59 yrs). Protein expression was analysed by immunohistochemical stain in paraffin embedded tissues with monoclonal antibody for p185HER2 (Oncogene).To explore the role of humanized anti-p185HER2 monoclonal antibody trastuzumab in vitro, the growth curve of the Korean gastric cancer cells which have different expression levels of the p185HER2 protein were studied and a cell cycle analysis was performed. p185HER2 overexpression is more frequent in AGC than EGC (p=0.008). p185HER2 overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01) and higher relapse rate (p=0.008).Patients with overexpression of p185HER2 have significantly lower relapse free (p=0.002) and overall survival (p=0.001) than patients without p185HER2 overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, SNU-620 overexpress p185HER2.Trastuzumab inhibited the proliferation of p185HER2 overexpressed Korean gastric cancer cell line by 21%, but did not inhibited the proliferation of SNU-16 which showed low p185HER2 expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase and G1 arrest following treatment with trastuzumab in p185HER2 overexpressed Korean gastric cancer cell line.Researchers concluded there is potential prognostic significance of p185HER2 overexpression in gastric adenocarcinoma patients. Antiproliferative effects of p185HER2 antibody can also be observed in Korean gastric cancer cell lines that overexpress this growth factor receptor, but the antiproliferative effect is relatively low compared with the effect in breast cancer cell line.If you would like more information on the HOTT congress please contact our office on (08) 9388 0344 or email us at adean@virtualcancercentre.com