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High incidence of ErbB3, ErbB4, and MET expression in ovarian cancer
Suzy Davies1, Anna Holmes, Lesley Lomo
1Departments of Obstetrics and Gynecology (S.D., C.Y.M.) Pathology (A.H., M.P.S., L.L., B.S.W.) Internal Medicine (H.K.) Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM (H.K., B.S.W).
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.
Insights
High expression of ErbB3, ErbB4, and MET in ovarian cancers suggests targeted therapies may benefit many patients. These growth factor receptors are frequently found in tumors, indicating broad therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Ovarian cancer remains a leading cause of gynecologic cancer mortality in the U.S.
- Tumor treatment resistance is often linked to complex growth factor receptor interactions.
- ErbB3-MET cooperativity is known to drive resistance to EGFR/ErbB2 inhibitors in solid tumors.
Purpose of the Study:
- To investigate the expression levels of MET and all four ErbB family members in ovarian cancer.
- To determine the potential for targeted therapies based on receptor expression patterns.
Main Methods:
- Analysis of tissue arrays from 202 ovarian carcinomas (Stage I-IV) and controls.
- Evaluation of expression for Epidermal Growth Factor Receptor (EGFR), ErbB2, ErbB3, ErbB4, and MET.
Main Results:
- Low expression of EGFR (25%) and ErbB2 (35%) was observed.
- High expression rates were found for ErbB3 (76%), ErbB4 (98%), and MET (96%).
- No significant correlation between ErbB3, ErbB4, or MET expression and patient outcome was identified.
Conclusions:
- The high prevalence of ErbB3, ErbB4, and MET suggests their broad applicability in ovarian cancer treatment.
- Targeted inhibitors against ErbB3, ErbB4, and/or MET represent a promising therapeutic strategy for this disease.
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