High incidence of ErbB3, ErbB4, and MET expression in ovarian cancer

Abstract

Ovarian cancer is the leading cause of death from gynecologic cancers in the United States. Failure may be due to variable expression and/or complex interactions of growth factor receptors in individual tumors. As ErbB3-MET cooperativity is implicated in solid tumor resistance to EGFR/ErbB2 inhibitors, we evaluated expression of MET and all 4 ErbB family members in ovarian cancers. Tissue arrays were prepared from archival formalin-fixed paraffin-embedded tumor samples, including 202 ovarian carcinomas (Stage I-IV) and controls. Of 202 patient samples, only 25% were positive for EGFR and 35% for ErbB2 expression. ErbB3, ErbB4, and MET showed marked expression in 76%, 98%, and 96% of cases. Consistent with high incidence, there was no significant correlation for expression of ErbB3, ErbB4, or MET with outcome. On the basis of their high expression in the majority of cases, inhibitors targeting ErbB3, ErbB4, and/or MET may be broadly applicable as therapeutic agents in this disease.

Figure 1

Validation of the ErbB3 antibody from MyBioSource using A and B) SkBr3 breast cancer cells; C and D) xenograft tumors excised from mice engrafted with SKOV3-ip.1 ovarian cancer cells that stably express ErbB3-GFP fusion proteins; and E and F) prostate cancer tissue.

Figure 2

Two representative ovarian cancer samples of different stage and histological types stained for ErbB1, ErbB2, ErbB3, ErbB4 and MET. Magnification is at 40X. Also included are positive control tissues used for each antibody stain.

Figure 3

Two representative ovarian cancer samples of different stage and histological type stained for ErbB3 and MET, with paired images of staining for their phosphorylated forms. The images show the assigned score for each sample. Magnification is at 40X.