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Background: In light of the coronavirus disease 2019 (COVID-19) pandemic, cancer centres in the United Kingdom and Europe re-organised their services at an unprecedented pace, and many patients with cancer have had their treatments severely disrupted. Patients with cancer were considered at high risk on sparse evidence, and despite a small number of emerging observational studies, the true incidence and impact of COVID-19 in the 'at-risk' population of patients with cancer is yet to be defined. Methods: Epidemiological and clinical data were collected prospectively for patients attending the Royal Marsden Hospital and three network hospitals between March 1st and April 30th 2020 that were confirmed to have Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Significance of clinical and pathological characteristics was assessed using the Fisher's exact test and Wilcoxon rank sum test, whilst univariate and multivariate logistic regression models were used to further assess risk. The number of patients attending in March/ April 2020 for face-to-face attendances was also extracted. Findings: During the 2-month study period, 867 of 13,489 (6.4%) patients met the criteria leading to swab testing. Of the total at-risk population, only 113 of 13,489 (0.84%) were swab positive, 101 of 13,489 (0.75%) required hospital admission and 29 of 13,489 (0.21%) died of

Background: Gestational trophoblastic neoplasia (GTN) after a hydatidiform mole is either treated with single- or multi-agent chemotherapy determined by a multifactorial scoring system. Women with human chorionic gonadotrophin (hCG) levels >100 000 IU l −1 can remain within the low-risk/single-agent category and usually choose one drug therapy. Here we compare the success and duration of single- vs multi-agent chemotherapy in this patient group. Methods: Between 1980 and 2008, 65 women had a pre-treatment hCG >100 000 IU l −1 and were low risk. The initial hCG level, treatment regimens, changes and duration and overall survival were recorded. Results: Of 37 patients starting low-risk/single-agent treatment, 11 (29.7%) were treated successfully, whereas 26 (70.3%) required additional multi-agent chemotherapy to achieve complete remission (CR). Combination chemotherapy was initially commenced in 28 women, and 2 (7%) required additional drugs for CR. The overall duration of therapy for those commencing and completing single- or multi-agent chemotherapy was 130 and 123 days ( P =0.78), respectively. The median-treatment duration for patients commencing single-agent but changing to multi-agent chemotherapy was 13 days more than those receiving high-risk treatment alone (136 vs 123 days; P =0.07). All 3 patients with an initial hCG >400 000 IU l −1 and treated with single-agent therapy developed drug resistance. Overall survival for all patients was 100%. Conclusion: Low-risk post-molar GTN patients with a pre-treatment hCG >100 000 and <400 000 IU l −1 can be offered low-risk single-agent therapy, as this will cure 30%, is relatively non-toxic and only prolongs treatment by 2 weeks if a change to combination agents is required. Patients whose hCG is >400 000 IU l −1 should receive multi-agent chemotherapy from the outset.

HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.Ovarian cancer is the 5th leading cause of cancer death in women in the western world and it is estimated there were 22,280 new cases and 15,500 deaths due to the disease in the US in 2012. 1 It is the most lethal of the gynaecological malignancies largely due to late diagnosis. Standard treatment involves debulking surgery followed by a combination of taxane and platinum-based therapy. Initially most women respond to platinum-based therapy, but the majority suffer disease recurrence due to drug resistance. It is therefore essential to introduce new therapeutic approaches to improve treatment at diagnosis and/or provide an effective second line treatment.There are different types of ovarian cancer classified by the cell type they originate from. The most common form, accounting for >90% of ovarian cancers, is epithelial ovarian cancer (EOC), and the high grade serous (HGS) subtype accounts for 80% of EOC cases.The epithelial ovarian tumours undergo M€ ullerian differentiation, which suggests that differentiation-regulatory factors may contribute to their progression. This mechanism has been shown to involve homeobox (HOX) genes 2,3 which play important roles in tissue differentiation during embryonic development. The HOX genes constitute a family of transcription factors, and in mammals 39 HOX genes have been identified. They are organised into 4 paralogous clusters (A, B, C and D) located on 4 different chromosomes. During development of the female reproductive system four HOX genes, HOXA9, HOXA10, HOXA11 and HOXA13 are expressed uniformly along the M€ uller...

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.

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Edited by Angel NebredaKeywords: Engrailed En1 En2 Homeodomain Cancer Biomarker Urinary a b s t r a c t Engrailed (En) is a member of the homeobox gene family, which encodes a homeodomain-containing transcription factor that is essential during early development. The only known site of normal adult Engrailed protein (EN) expression is in the nervous system, and it has been implicated in the development of both young-onset Parkinson's disease as well as autism. Over-expression of EN has been linked to tumour development in adults, particularly in breast, prostate, melanoma and ovarian cancers, and there is a growing interest in its role as a diagnostic and prognostic biomarker. It is hoped that further work may confirm associations between En expression and therapy-resistant, poor prognosis cancers, similar to that identified with other homeobox gene profiles.

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