cMet and Her2 as markers of cancer risk in Barrett’s patients

Abstract

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Barrett’s esophagus (BE) is a pre-neoplastic condition linked to the development of esophageal adenocarcinoma. Understanding the molecular pathways involved in progression from BE to cancer is key to advancing early detection and therapy. Her2 and cMet act upstream of signaling pathways with key roles in tumorigenesis. Overexpression of these receptors is linked to different types of epithelial cancers, and recently cMet has been reported to be overexpressed in esophageal cancer. We have examined the expression of these receptors in a collection of 107 biopsies representing all stages of esophageal carcinogenesis.
Immunohistochemical analysis demonstrated that cMet levels are low in normal tissue, and strongly upregulated in metaplastic, dysplastic and to a lesser extent carcinoma tissue. However, this profile cannot be related to malignant progression of BE, as cMet was highly expressed in all BE patients, regardless of progression to higher risk stages.
Her2 expression was found to be minimal in normal tissue, accompanied by strong staining in BE & high grade dysplasia, weak staining in low grade dysplasia and variable staining in adenocarcinoma samples. Interestingly Her2 expression was higher in BE tissue adjacent to dysplasia or carcinoma. Staining intensity increased with the severity of the adjacent lesion, pointing to a possible link between Her2 and disease progression. Whether increased Her2 in BE is the cause or the effect of dysplasia/cancer is not certain; however this data suggests that the molecular events underlying progression to adenocarcinoma are linked to the Her2 pathway.
In conclusion, our studies indicate that cMet expression in BE patients is complex and does not appear to be linked to the development of adenocarcinoma, while increased Her2 expression in metaplastic tissue maybe associated with the formation of metaplasia, dysplasia and adenocarcinoma. These findings highlight the need for better understanding of the role of the Her2 pathway in esophageal cancer.