EGFR Protein Expression and Genetic Amplification in High-Grade Pleomorphic Uterine Sarcomas
Jingxuan Huang, Adam Smith, Cheng-Han Lee. University of British Columbia, Vancouver, BC, Canada; BC Cancer Agency, Vancouver, BC, Canada
Background: Epidermal growth factor receptor (EGFR) is known to be frequently expressed in undifferentiated endometrial sarcomas (UES) and the sarcomatous component of malignant mixed mullerian tumors (MMMT or carcinosarcoma), but little is known regarding its genetic basis. Only a single case of UES with EGFR amplification which showed a significant but temporary response to imatinib has been previously reported (Ann Diagn Pathol. 2007;11(1):49-54). The aim of the current study is to evaluate EGFR copy number and amplification status in a series of non-smooth muscle high-grade pleomorphic uterine sarcomas.
Design: We identified a series of 14 high-grade non-smooth muscle primary uterine sarcomas (hysterectomy specimens) through retrospective review of pathology archive at Vancouver General Hospital since 2000. All cases demonstrated high-grade nuclear features with diffuse and marked nuclear pleomorphism and none showed features of endometrial stromal sarcoma. These included 8 UES, 4 uterine sarcomas with rhabdomyosarcomatous differentiation (US-RMS), 1 uterine sarcoma with osteosarcomatous differentiation (US-OSA) and 1 adenosarcoma that is nearly completely overgrown by high-grade undifferentiated sarcomas (US-AD). EGFR (Dako) immunostaining was performed on representative whole sections and scored using Her-2/neu scoring criteria for breast cancer. Fluorescence in situ hybridization (FISH) for EGFR and CEP7 (LSI EGFR/CEP7, Abbott Molecular, 40 tumor nuclei evaluated) was performed in cases that showed 3+ EGFR protein expression.
Results: Seven of the 14 cases showed 3+ EGFR protein expression (4 UES, 2 US-AD, 1 US-RMS and 1 US-OSA). Interpretable FISH was obtained in five cases with 3+ EGFR staining with the remaining two cases to be repeated (data pending). Among these 5 cases, one case (US-OSA) showed EGFR amplification (EGFR/CEP7 ratio 2.07) while the 3 other cases (1 UES, 1 US-RMS and 1 US-AD) showed increased EGFR copy numbers in >50% of the nuclei evaluated with similar corresponding increase in CEP7 signals.
Conclusions: A significant subset of non-smooth muscle high-grade uterine sarcomas strongly expresses EGFR and the data here suggest that EGFR amplification or increased copy number appear to be the underlying genetic mechanism for the observed protein expression. These findings, together with the prior reported case of EGFR-amplified UES provide a compelling rationale for therapeutic targeting of EGFR in these high-grade uterine sarcomas.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 183, Monday Morning