The prognostic significance of human epidermal growth factor receptor correlations in squamous cell cervical carcinoma.

The aim of this study was to investigate the expression and prognostic influence of HER1 (EGFR), HER2 (c-erb-B2), HER3 (c-erb-B3) and HER4 (cerb-B4) in squamous cell cervical carcinomas (SCC) and the importance of receptor correlations. Patients and Methods: 78 SCC were stained immunohisto- chemically for HER1-HER4. HER2 gene amplification was determined using fluorescence in situ hybridization (FISH). Parametric correlations were performed between the four receptors and tumor characteristics. Overall survival was evaluated by uni- and multivariate analyses. Results: Overexpression was found in 63% of SCC for HER1, in 21.8% for HER2, in 74.4% for HER3 and in 79.5% for HER4. Correlations were observed between HER1 and HER4 (p=0.019). Survival analyses revealed a significant association of HER1 overexpression with favorable outcome (p=0.016), while overexpression of HER2 and HER3 was associated with poor prognosis (p=0.006; p=0.05, respectively). HER1 remained significant in multivariate analysis. Conclusion: These data suggest that the prognostic relevance of the different HER receptors is influenced by the balance between the various receptors, especially of HER4. Carcinoma of the uterine cervix remains the leading cause of cancer death in young women. In aggressive disease, a multimodal treatment approach includes platinum-based chemotherapy next to surgery and radiation, however, the efficacy of systemic treatment in this tumor entity is very limited (1). The identification of new therapeutic targets is therefore a major goal in improving patient outcome. The four members of the human epidermal growth factor receptor (HER) family: HER1 (EGFR, erbB1), HER2 (erbB/neu), HER3 (erbB3) and HER4 (erbB4) are transmembrane tyrosine kinases which take part in the regulation of cell proliferation, adhesion, migration and differentiation (2). Receptor activation and signal transduction act through homo- and heterodimerisation. The formation of various dimeric pairs is dependent on the affinity between the different receptors and the concentration of both ligands and receptors (3, 4). The specific pattern of the heterodimeric pairs seems to modulate the intracellular response. Receptor overexpression, especially of HER1 and HER2 has been associated with malignant potential and poor prognosis in various tumors (5).