Abstract
The human epidermal growth factor receptor (EGFR) is an important therapeutic target in patients with metastatic colorectal cancer and anti-EGFR antibodies cetuximab and panitumumab have been approved for the treatment of such patients. Despite these advances, the duration of response in some patients can be limited. Since, EGFR is capable of forming heterodimers with the other members of the HER (Human epidermal receptor) family, it is important to investigate the co-expression and prognostic significance of all members of the HER family in colorectal cancer patients. The expression of the HER family members were determined in tumour specimens from 86 patients with Dukes’ C and D (metastatic) colon cancer using immunohistochemistry. Sections were scored by the percentage of positive tumour cells and intensity of staining. Their associations with clinicopathological parameters, and overall survival and disease free survival were evaluated using univariate and multivariate analysis. Overall, 43%, 77%, 52% and 92% of the cases were EGFR, HER-2, HER-3 and HER-4 positive respectively. Interestingly, 35%, 24%, 43%, and 18% of the cases had co-expression of EGFR/HER-2, EGFR/HER-3, EGFR/HER-4 and all four members of the HER family respectively. Of these, only the expression of EGFR and co-expression of EGFR/HER-4 were associated with poorer disease-free survival in both univariate and multivariate analysis. Co-expression of all members of the HER family in colon cancer supports the need for further investigations on their predictive value for response to therapy with anti-EGFR mAbs and whether such sub-population of patients may benefit from therapy with the new generation of pan-HER inhibitors.
Highlights
Colorectal cancer remains one of the leading causes of cancer deaths worldwide
Of the various drugs developed for the targeted therapy of human cancers, the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, cetuximab and panitumumab, and the anti-vascular endothelial growth factor (VEGF) mAb bevacizumab have been incorporated into treatment paradigms for the majority of patients with metastatic colorectal cancer [2,3,4,5]
Members At cut off value of $5%, tumour specimens from 43%, 77%, 52% and 92% of cases were EGFR, HER-2, HER-3 and HER-4 positive respectively (Table 2)
Summary
Colorectal cancer remains one of the leading causes of cancer deaths worldwide. In 2013, colorectal cancer is estimated to be the fourth most commonly diagnosed cancer (142,820) but the second leading cause of cancer deaths (50,830) after lung cancer in the USA [1]. Of the various drugs developed for the targeted therapy of human cancers, the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs), cetuximab and panitumumab, and the anti-vascular endothelial growth factor (VEGF) mAb bevacizumab have been incorporated into treatment paradigms for the majority of patients with metastatic colorectal cancer [2,3,4,5]. The development and identification of such markers could aid in the selection of a more specific subpopulation of colorectal cancer patients who are more likely to benefit from such therapies, but they may reduce unnecessary treatments and thereby the high cost to the healthcare system [11]
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