Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma

Abstract

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero-and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours coexpressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.

A quantifier-based fuzzy classification system for breast cancer patients

“…This has led to a more 'clinically acceptable' classification, with the proportion of HER2-positive patients ranging between 12.5% and 15% and the total number of unclassified patients being only 3.5% of the available cases. The distribution and percentages of breast cancer patients into the three big classes of luminal, basal and HER2 were established in a seminal study by Sorlie et al [6] and confirmed by subsequent papers [52][53][54]. The method described here has produced a breast cancer classification consistent with the proportion of cancer subtypes reported in other studies.…”

The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients

“…Several reports, based mainly on the expression of HER1 and HER2, demonstrate that the EGF family of receptors are involved in poor prognosis in various cancers including bladder cancer (Lonn et al, 1995;Arpino et al, 2004;Blackwell et al, 2004;Popov et al, 2004). In contrast to HER1 and HER2, our study on bladder tumours (Memon et al, 2004) and other studies on breast tumours (Abd El-Rehim et al, 2004) have suggested that increased expression of HER3 and HER4 is associated with improved survival. This is supported by data on cancer cells that demonstrate a ligand-dependent proapoptotic function of the HER4-expressing cells (Sartor et al, 2001).…”

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

“…This study included 31 biomarkers of clinical and biological relevance to BC tumourigenesis and progression [9,11] Primary Breast Carcinoma series previously studied using gene expression profiling [14].…”