Co-expression and prognostic significance of the HER family members, EGFRvIII, c-MET, CD44 in patients with ovarian cancer

Abstract

EGFR and HER-2 are important targets but none of the monoclonal antibodies or small molecule tyrosine kinase inhibitors specific for the HER members has been approved for the treatment of patients with ovarian cancers. In some studies, co-expression of other growth factor receptors has been associated with resistance to therapy with the HER inhibitors. The aim of the present study was to determine the relative expression, cellular location, and prognostic significance of HER-family members, the EGFR mutant (EGFRvIII) c-MET, IGF-1R and the cancer stem cell biomarker CD44 in 60 patients with FIGO stage III and IV ovarian cancer. At cut off >5% of tumour cells with positive staining, 62%, 59%, 65% and 45% of the cases were EGFR, HER-2, HER-3 and HER-4 positive, and 3%, 22% and 48.3% of the cases were positive for EGFRvIII, c-MET, and CD44 respectively. Interestingly, 23% co-expressed all four members of the HER family. On univariate analysis, only EGFR staining at >50% of tumour cells (HR = 3.57, p = 0.038) and CD44 staining at 3+ intensity (HR = 7.99, p = 0.004) were associated with a poorer overall survival. EGFR expression (HR = 2.83, p = 0.019) and its co-expression with HER-2, HER-3, HER-2/HER-3, and c-MET were all associated with poorer disease-free survival. Our results suggest co-expression of the HER-family members is common in Stage III and IV ovarian cancer patients. Further studies on the prognostic significance and predictive value of all HER family member proteins for the response to treatment with various forms of the HER inhibitors are warranted.