Effect of Epidermal Growth Factor Receptor Expression Level on Survival in Patients with Epithelial Ovarian Cancer

Abstract

Background: Several lines of laboratory evidence support the epidermal growth factor receptor (EGFR) as an adverse prognostic indicator in ovarian cancers. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of EGFR in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Methods: A tissue array composed of 150 advanced-stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of EGFR protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Results: Mean follow-up time for the entire cohort was 34.4 months. Eighty-one of 150 cases had sufficient tissue for AQUA analysis. High tumor EGFR expression was associated with poor outcome for overall survival (P = 0.0001) and disease-free survival (P = 0.0005) at 3 years. In multivariable analysis, adjusting for well-characterized prognostic variables, EGFR expression status was the most significant prognostic factor for disease-free and overall survival. Conclusion: The conflicting results in the literature regarding the prognostic value of EGFR may be due to the technical difficulties inherent in assessing EGFR with immunocytochemistry. In the present study, we show that measurement of EGFR protein levels in ovarian cancer using AQUA is feasible and can give important prognostic information.

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer

“…We did not observe any association between EGFR and HER-2/ neu immunostaining and disease outcome, confirming results of a previous study also from our institution (Van Der Zee et al, 1995). Previous studies on the relationship between EGFR or HER-2/neu overexpression and clinicopathological characteristics, response to chemotherapy and survival have shown conflicting results Elie et al, 2004;Nielsen et al, 2004;Psyrri et al, 2005). One of the most important reasons for these inconclusive data is the considerable methodological variability among studies (Hall et al, 2004).…”

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates

“…Cetuximab, an anti-EGFR monoclonal antibody (mAb), targets cancer cells overexpressing EGFR. EGFR is an important molecule for targeting cancer cells that displays elevated expression in up to 70% of EOCs (33) and in many other carcinomas (34) (SI Text, Note S4). Although EGFR targeting is the focus here, immunoconjugate synthesis, imaging, and taPIT are all generalizable such that a variety of targeting molecules for other tumor antigens may be applied (SI Text, Note S2).…”

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

“…The results of the studies evaluating the prognostic role of EGFR expression are also conflicting. Some studies suggested EGFR positivity as a negative prognostic factor (Skirnisdottir et al, 2001;Psyrri et al, 2005;Lassus et al, 2006;Noske et al, 2011) and demonstrated an association with poorer survival rates, while others reported no relationship between disease outcome and EGFR expression (Nielsen et al, 2004;de Graeff et al, 2008). Variations in IHC procedures, antibodies, and patient selection may provide some explanation for the differing results from these studies.…”