Abstract
BackgroundEpithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker.MethodsWe evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009–2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/−resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry).ResultsEn2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p = 0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p = 0.0103).ConclusionThe EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.
Highlights
Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker
EN2 expression in epithelial ovarian cancer cell lines RNA was extracted from cultures of 8 serous Epithelial ovarian cancer (EOC) cell lines, with the platinum-sensitivity status recorded for each of these
PEO1 represented a cell line derived from a platinum-sensitive, serous ovarian carcinoma
Summary
Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. The symptoms of ovarian cancer are often very vague and may be misinterpreted as those of more common, benign conditions As these symptoms are mostly related to the pressure effects of the growing tumour mass, they may only present when the primary mass is already very. Many women with advanced EOC at diagnosis will experience a good initial response to platinum-based chemotherapy and surgery, and may have a prolonged disease-free interval, but often relapse with either. There is increasing research into prognostic and treatment response biomarkers, especially focussing on the identification of molecular signatures that may indicate the early development of platinum-resistant disease. Et al demonstrated that high expression of HOXA13, B6, C13, D1 and D13 were predictive of poor clinical outcome in EOC [9]. PAX8, is consistently over-expressed in high grade serous ovarian carcinomas but negative in breast adenocarcinoma so is often used by the pathologist to help determine the origin of certain pelvic serous tumours, especially if the primary tumour source is not always clearly evident [11,12,13]
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