Research Papers:

The status of epidermal growth factor receptor in borderline ovarian tumours

Rania Showeil, Claudia Romano, Mikel Valganon, Maryou Lambros, Pritesh Trivedi, Susan Van Noorden, Ruethairat Sriraksa, Dalal El-Kaffash, Nour El-Etreby, Rachael Natrajan, Letizia Foroni, Richard Osborne and Mona El-Bahrawy _

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Oncotarget. 2016; 7:10568-10577. https://doi.org/10.18632/oncotarget.7257

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Rania Showeil1,2, Claudia Romano3, Mikel Valganon3, Maryou Lambros4, Pritesh Trivedi1, Susan Van Noorden1, Ruethairat Sriraksa5, Dalal El-Kaffash2, Nour El-Etreby6, Rachael Natrajan4, Letizia Foroni3, Richard Osborne7, Mona El-Bahrawy1,8

1Department of Histopathology, Imperial College London, London, United Kingdom

2Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

3Imperial Molecular Pathology Laboratory, Imperial College London, London, United Kingdom

4Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom

5Epigenetics Group, International Agency for Research on Cancer, Lyon CEDEX 08, France

6Obstetrics and Gynaecology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

7Dorset Cancer Centre, Poole Hospital, Dorset, United Kingdom

8Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Correspondence to:

Mona El-Bahrawy, e-mail: [email protected]

Keywords: EGFR, borderline ovarian tumours

Received: August 20, 2015     Accepted: January 23, 2016     Published: February 8, 2016


The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours.

We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations.

Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs.

Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs.

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