Strong nuclear EGFR expression in colorectal carcinomas is associated with cyclin-D1 but not with gene EGFR amplification

BACKGROUND: Prognostic and predictive significance of epidermal growth factor receptor (EGFR) in colorectal carcinomas (CRCs) is still controversial. The aim of the present study was to explore and correlate membrane and nuclear EGFR and cyclin-D1 protein expression with EGFR gene status of tumor cells. METHODS: Immunohistochemical and FISH analysis was performed on 135 archival formalin fixed and paraffin embedded CRCs. RESULTS: Strong membrane and strong nuclear EGFR staining was detected in 16% and 57% of cases, respectively, and strong cyclin-D1 expression in 57% samples. Gene EGFR amplification was identified in 5.9% and polysomy in 7.4% of cases, while 87% showed no EGFR gene changes. A statistically significant difference was only found between tumor grade and expression of membrane EGFR, while nuclear EGFR and cyclin-D1 expression was not associated with the clinicopathologic characteristics analyzed. Tumor cells displaying gene amplification and strong protein membrane EGFR expression overlapped, while EGFR gene status showed no correlation with nuclear EGFR and cyclin-D1. There was no association between membrane EGFR and cyclin-D1, whereas nuclear EGFR expression was strongly related to cyclin-D1 expression. CONCLUSIONS: Study results revealed heterogeneity among CRCs, which could have a predictive value by identifying biologically and probably clinically different subsets of tumors with the possibly diverse response to anti-EGFR therapies.