c-erbB-2 is not a major factor in the development of colorectal cancer

Abstract

We have investigated c-erbB-2 protein expression in a large cohort of well-characterized colorectal tumours, and in a subset of lymph node metastases. We have also evaluated a Val(655)Ile single nucleotide polymorphism, which is associated with an increased risk of breast cancer, in a subset of the colorectal cancer patients and in healthy control subjects. Immunohistochemical studies revealed that while 81.8% of tumours expressed c-erbB-2, in the majority of cases equivalent levels of c-erb-B2 were seen in adjacent normal mucosa. Colon tumours were significantly more likely to express c-erbB-2 than rectal tumours (P=0.015). Only 52.4% of the metastases displayed staining patterns concordant with their primary tumour, indicating that determination of c-erbB-2 protein in colorectal tumours cannot predict the status of lymph node metastases. PCR--RFLP analysis of the Val(655)Ile single nucleotide polymorphism demonstrated that allele frequencies were identical between colorectal cancer patients and a control group of Caucasian subjects (Ile=0.80 and Val=0.20 in each case), indicating that it is not related to the risk of developing colorectal cancer in this population. Furthermore, there was no relationship between c-erbB-2 protein expression and gene polymorphism (P=0.58). In terms of prognosis, no association was seen between either c-erbB-2 protein expression or the presence of the Val allele and patient survival (P>0.05 in each case), suggesting that c-erbB-2 is not a prognostic marker in colorectal cancer.

Figure 1

PCR–RFLP analysis of the c-erbB-2 Val⁶⁵⁵Ile SNP.

Figure 2

Representative examples of (A) strong membranous staining of tumour cells, and (B) negative immunoreactivity for c-erbB-2, in primary colorectal adenocarcinomas.

Figure 3

Kaplan–Meier plots of the effects on colorectal cancer patient outcome of (A) c-erbB-2 protein expression, and (B) the Val⁶⁵⁵Ile SNP. Neither of these factors were found to influence survival (P>0.05 in each case).