HER expression in gastric cancers defined
MedWire News: All members of the human epidermal growth factor (HER) receptor are expressed in gastric cancers, with HER2 and HER3 linked particularly strongly with poor survival, results published in the Journal of Clinical Oncology show.
"In gastric carcinomas, HER1 and HER2 overexpression is thought to be a prognostic factor and target of novel biologic agents; however, the clinical significance of such overexpression is not yet fully clear, and not all studies have shown an association between HER2 overexpression and poor prognosis," say Maria Begnami (Hospital AC Carnargo, São Paulo, Brazil) and colleagues.
The influence of HER3 and HER4 expression on gastric cancer outcomes is also unclear, although studies have suggested that HER3 and HER4 expression is increased in gastric cancer tissue relative to surrounding tissues, and that HER3 expression is associated with poor prognosis.
Noting this, Begnami and team assessed HER family expression in primary gastric tumor tissue from 221 patients.
The analysis identified HER1-positive tumors in 2% of patients and, based on this small sample, the authors found no significant links between HER1 expression and tumor characteristics or patient outcomes. Overexpression of HER2 was more common and detected in 12% of patients.
Unlike HER1 expression, HER2 overexpression, seen in 12% of patients, was significantly associated with reduced overall survival.
Testing for HER3 revealed expression throughout the sample tissues, with expression in the cytoplasm in 64% of samples, in the nuclei in 34% of samples, and in the membrane of less than 1% of the samples. Cytoplasmic and nucleic expression of HER3 was most common in intestinal-type tumors, but nuclear HER3 expression alone significantly predicted vascular and lymphatic invasion.
Expression of HER3 in cell nuclei was significantly associated with decreased overall survival rates.
Finally, the researchers found that HER4 was expressed in the cytoplasm of 23% of tumor tissue samples, in the membranes of 18%, and in the nuclei of 2%.
Again, cytoplasmic and nucleic HER4 expression predicted intestinal-type tumors, and cytoplasmic expression was associated with well- and moderately differentiated tumors. HER4 expression had no significant influence on overall survival, however.
"Our study provides evidence that both gene and protein expression of the HER family, especially HER2 and HER3, are significant predictors of poor survival in gastric cancer," summarize Begnami and team.
"Therefore, the development of new predictive markers, analyzing dimers rather than isolated markers, could introduce a new way of understanding these interactions and help us understand the importance of the HER family with regard to the biology and behavior of gastric cancer," the researchers write.
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By Philip Ford