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Epithelial growth factor receptor status in primary and recurrent ovarian cancer
Sylvia Stadlmann1, Uwe Gueth, Ulrich Reiser
1Institute for Pathology, University Hospital of Basel, Basel, Switzerland.
Abstract:
Success of epidermal growth factor receptor (EGFR) targeting agents in different cancer types is related to EGFR gene mutations and/or copy number gains. We investigated the EGFR gene status and protein expression by DNA mutational analysis, fluorescence in situ hybridization (FISH), and immunohistochemistry in tumor tissues from 80 patients with primary and corresponding recurrent ovarian serous carcinomas. The patients were classified into six groups with ascending EGFR gene copy numbers. EGFR amplification and high polysomy (FISH+) was present in a significant fraction of the primary (20%) and recurrent (22%) ovarian carcinomas. On mutational analysis, only one tumor with a silent EGFR mutation was observed, and this was the only carcinoma with high-level amplification. EGFR protein immunoexpression was seen in 28% of primary and 33% of recurrent carcinomas and correlated to amplification in the primary tumors (P = 0.003). In recurrent carcinoma, moderate and strong EGFR expression was associated with amplification (P = 0.034). These molecular events potentially have impact on the responsiveness to EGFR targeting agents in ovarian cancer.
Insights
Epidermal growth factor receptor (EGFR) amplification and protein expression were analyzed in ovarian cancer. These findings suggest potential impacts on treatment response to EGFR-targeting agents.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeting agents for epidermal growth factor receptor (EGFR) show success in various cancers, linked to EGFR gene mutations and copy number gains.
- Ovarian serous carcinoma is a significant health concern, and understanding its molecular underpinnings is crucial for effective treatment.
Purpose of the Study:
- To investigate the EGFR gene status and protein expression in primary and recurrent ovarian serous carcinomas.
- To determine the prevalence of EGFR amplification and mutations in ovarian cancer.
- To explore the correlation between EGFR molecular alterations and protein expression.
Main Methods:
- DNA mutational analysis was performed on tumor tissues.
- Fluorescence in situ hybridization (FISH) was used to assess EGFR gene copy numbers.
- Immunohistochemistry (IHC) was employed to evaluate EGFR protein expression.
Main Results:
- EGFR amplification and high polysomy (FISH+) were observed in 20% of primary and 22% of recurrent ovarian carcinomas.
- A single silent EGFR mutation was detected in one tumor with high-level amplification.
- EGFR protein expression was present in 28% of primary and 33% of recurrent carcinomas, correlating with amplification in both primary and recurrent tumors.
Conclusions:
- EGFR amplification and protein expression are present in a significant subset of ovarian serous carcinomas.
- These molecular alterations may influence patient response to EGFR-targeting therapies.
- Further research is warranted to elucidate the therapeutic implications of EGFR status in ovarian cancer.
