Overexpression of HER-2/neu in patients with colorectal cancer (CC) and colorectal adenomas (CP)

Introduction: HER-2/neu gene overexpression has been observed in many cancers and correlated with their clinical agressiveness. It’s prognostic value in breast cancer has been documented. The differences in proximal and distal colon histology, biology and neoplasia have been shown. Mucosal genetic abnormalities have been observed in full length of the neoplastic colon. Material and meethods: The aim of the study was to analyse the colonic mucosal HER-2/neu gene expression in patients with CC and CP of proximal and distal location. Twenty four patients with colorectal adenocarcinoma and 37 with adenomatous polyps have been included into the study. In 13 cases CC was located proximally and in 11 – distally. Five tumors were well differentiated (G1), 18 – moderately differentiated (G2) an one poorly differentiated (G3). CC stage, based on Duke’s scale was: A – in 8 , B – in 7, C – 6 and D – in 3 patients. In eleven patients adenomas were located proximally, in 17 - distally and in 9 in both segments of the colon. Seventeen patients had tubular adenoma, 19 – mixed and one villous adenoma. High grade dysplasia (HGD) was observed in 16 cases. Control group consisted of 40 subjects with no organic colorectal disease. Biopsy specimen have been taken from normally appearing mucosa, subjected to DNA isolation and PCR analysis. Result: Her2/neu overexpression has been observed in 17 CC patients (71%). In A group according to Duke’s scale it was found in 50% and B,C and D together - in 81% patients. In distally located tumors Her2/neu overexpression has been observed in 54% cases (6/11) and in proximal - in 85% of them (11/13) (p<0,05). In patients with CP Her-2/neu overexpression was found in 16 cases (43%) with similar incidence in proximal than distal colon (45% vs. 35%). When adenomas were located in both colonic segments Her-2/neu overexpression was observed in 78% cases. No Her-2/neu overexpression in control group has been found. Conclusion: Her2/neu overexpression was observed in macroscopically unchanged colonic mucosa in most patients with CC, particularly of proximal location and correlated with more advanced CC stage. Similarly, it was observed more often in patients with proximal than distal CP. Her2/neu overexpression may play a role in proximal colon neoplasia. (Clin Exp Med Lett 2009; 50(3):179-182)

Keywords: colon cancer, Her-2/neu, overexpression, colon polyps