Abstract
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.
Highlights
Colorectal cancer (CRC) is one of the most common types of tumor and is the fourth leading cause of cancer mortality worldwide [1]
The positive rates of human epidermal growth factor receptor 2 (HER‐2) overexpression may have varied in these studies due to differences in the IHC procedure, sample size and the scoring system employed
Demirbas et al [11] demonstrated HER‐2 overexpression in 9.6% of 104 patients with CRC using tissue microarray (TMA). The results of these studies indicate that the expression of HER‐2 in CRC is associated with the prognosis and may constitute a potential candidate for novel adjuvant therapies involving humanized monoclonal antibodies, such as Herceptin
Summary
Colorectal cancer (CRC) is one of the most common types of tumor and is the fourth leading cause of cancer mortality worldwide [1]. With economic development and changes in lifestyle, the incidence and mortality rates of CRC have rapidly increased in China. With the exception of surgery, the majority of treatments for CRC, including traditional chemo‐ and radiation therapies, are not fully efficacious in treating the disease. The recent development of novel drugs targeting CRC has improved the survival rate of patients with the disease. Targeted drugs for the treatment of cancer have rapidly developed. HER‐2‐targeted drugs, including Herceptin, have been developed and widely applied for the treatment of breast cancer presenting with membranous HER‐2 overexpression [3,4]
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