Significance of human epidermal growth factor receptor 2 expression in colorectal cancer

The aim of the present study was to evaluate the protein expression level of human epidermal growth factor receptor 2 (HER-2) using immunohistochemistry (IHC), and assess the association with clinicopathological parameters and the prognosis of patients with colorectal cancer (CRC). In addition, the current study observed the consistency between the levels of HER-2 protein expression determined by IHC and HER-2 gene amplification determined by fluorescence in situ hybridization (FISH) in the CRC samples. Overexpression of HER-2 and gene amplification were examined with semiquantitative standardized IHC in 878 formalin-fixed paraffin-embedded CRC samples, while 102 of these cases were analyzed with FISH. A total of 102 cases (11.6%), out of the 878 cases, were determined by IHC to overexpress HER-2. Of these, 25 cases were strongly positive (IHC3+), while 77 cases revealed moderate staining (IHC2+). HER-2 overexpression was more frequent in early-stage cases compared with advanced-stage cases of CRC (P<0.001). However, there was no association observed between HER-2 overexpression and clinicopathological parameters. FISH analysis revealed that 64% (16/25) of the IHC3+ cases had HER-2 gene amplification. By contrast, only 6.5% (5/77) of the IHC2+ cases, and none of the 20 randomly selected IHC0 or 1+ cases, demonstrated HER-2 gene amplification. Furthermore, no associations were observed between HER-2 overexpression or gene amplification with the survival time. Thus, the present study observed that HER-2 overexpression does not correlate with other clinicopathological data or the survival rate, with the exception of clinical stages. However, IHC3+ and 2+ cases should be further analyzed by FISH to assess the status of the HER-2 gene in CRC. Patients with HER-2 gene amplification may constitute as potential candidates for targeted therapy with trastuzumab.