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 655Ile 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 (P40.05 in each case), suggesting that c-erbB-2 is not a prognostic marker in colorectal cancer.

Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study

“…Studies that scored intracytoplasmic staining as positive reported larger frequencies, whereas studies that reported only membrane staining as positive was scored lower or zero frequency. [16][17][18][19][22][23][24] The results of the current study appear similar to those of Osako et al, 22 who used the same antibody as in our study. They observed membranous staining in only 3% of colorectal carcinomas (three of 100), and demonstrated gene amplification by Southern blot analysis in one of the three.…”

“…Previous IHC studies examining HER-2 expression reported different percentages of positive cells, ranging from 0 to 100%. [16][17][18][19][20][21][22][23][24] The major cause of these discrepancies seems to be the different criteria for evaluating the results. Studies that scored intracytoplasmic staining as positive reported larger frequencies, whereas studies that reported only membrane staining as positive was scored lower or zero frequency.…”

Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer

“…Many studies have investigated expression levels of cell cycle proteins and clinical outcome in colorectal cancer patients reporting conflicting results. 22,[42][43][44][45][46][47][48][49][50] Most studies describe heterogeneous patient populations without stratification for tumor localization (colon vs. rectum) and MSI status and without multivariate analysis. Furthermore, the choice of scoring method and selection of cutoff values for immunoreactivity is rarely described.…”

Prognostic significance of the p185 protein in colorectal cancer

“…However, there are many doubts about the prognostic significance of this oncogene in colorectal tumors (13)(14)(15)(16). While authors such as McKay et al (18) or Webb et al (19) found that cerbB-2/neu was of no prognostic value, others including Kay et al (10), Kapitanovic et al (11), and Osako et al (12) (11).…”