Radiotherapy is not indicated in patients with vulvar squamous cell carcinoma and only one occult intracapsular groin node metastasis.

OBJECTIVE: Most guidelines advise no adjuvant radiotherapy in vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis. However, several recent studies have questioned the validity of this recommendation. The aim of this study was to analyze the groin recurrence rate in patients with a single intracapsular positive lymph node treated without adjuvant radiotherapy. METHODS: Patients with a single clinically occult intracapsular lymph node metastasis, treated without adjuvant radiotherapy, formed the basis for this study. Groin recurrences, and the risk of death, were analyzed in relation to the size of the metastasis in the lymph node and the lymph node ratio. Data were analyzed using SPSS, version 26.0 for Windows. RESULTS: After a median follow-up of 64 months, one of 96 patients (1%) was diagnosed with an isolated groin recurrence and another two (2.1%) were diagnosed with a combination of a local and a groin recurrence. The only isolated groin recurrence occurred in a contralateral lymph node negative groin. Size of the metastasis and lymph node ratio had no impact on the groin recurrence risk, nor on survival. The 5-year actuarial disease-specific and overall survivals were 79% and 62.5% respectively. The 5-year actuarial groin recurrence-free survival was 97%. CONCLUSION: Because of the low risk of groin recurrence and the excellent groin recurrence-free survival, we recommend that adjuvant radiotherapy to the groin in patients with vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis can be safely omitted to prevent unnecessary toxicity and morbidity.

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer.

BACKGROUND: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. METHODS: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. RESULTS: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. CONCLUSIONS: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care.

INTRODUCTION: The International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65-74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities. OBJECTIVE: To compare clinical practice guidelines and patterns of care across seven high-income countries. METHODS: A comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by 'distant' stage using Spearman's rho. RESULTS: Twenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/'ultra-radical' surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits. DISCUSSION: Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

Hereditary gynaecologic cancers in Nepal: a proposed model of care to serve high risk populations in developing countries.

BACKGROUND: Endometrial, ovarian and breast cancers are paradigms for global health disparity. Women living in the developing world continue to present in later stages of disease and have fewer options for treatment than those in developed countries. Risk reducing surgery is of proven benefit for women at high risk of gynaecological cancer. There is no specific model for identification and management of such women in the developing world. METHODS: We have integrated data from our published audit of a major gynaecological oncology centre at Royal Hospital for Women in Australia, with data from our survey and a focus group discussion of Nepalese gynaecological health care professionals regarding genetic testing, and findings from the literature. These data have been used to identify current barriers to multidisciplinary gynaecological oncology care in developing nations, and to develop a model to integrate hereditary cancer services into cancer care in Nepal, as a paradigm for other developing nations. RESULTS: The ability to identify women with hereditary gynaecological cancer in developing nations is influenced by their late presentation (if active management is declined or not appropriate), limited access to specialised services and cultural and financial barriers. In order to include genetic assessment in multidisciplinary gynaecological cancer care, education needs to be provided to all levels of health care providers to enable reporting of family history, and appropriate ordering of investigations. Training of genetic counsellors is needed to assist in the interpretation of results and extending care to unaffected at-risk relatives. Novel approaches will be required to overcome geographic and financial barriers, including mainstreaming of genetic testing, telephone counselling, use of mouth swabs and utilisation of international laboratories. CONCLUSION: Women in Nepal have yet to receive benefits from the advances in early cancer diagnosis and management. There is a potential of extending the benefits of hereditary cancer diagnosis in Nepal due to the rapid fall in the cost of genetic testing and the ability to collect DNA from a buccal swab through appropriate training of the gynaecological carers.

Improved Detection Rate of Ovarian Cancer Using a 2-Step Triage Model of the Risk of Malignancy Index and Expert Sonography in an Outpatient Screening Setting.

OBJECTIVE: Preoperative assessment of adnexal masses with ultrasound has been shown to be time-, cost-effective, and specific. When used in combination with the menopausal status and the tumor marker CA125, the risk of malignancy index (RMI) can be calculated, allowing appropriate preoperative triage of patients to a gynecologist or a gynecological oncologist. Moreover, it allows for accurate planning of the required surgical procedure (laparoscopy vs laparotomy). METHODS: A large general gynecologic ultrasonic database retrospectively identified 5218 patients for a 14-year period who presented to the outpatient clinic with an adnexal mass. Additional data (menopausal status, histology, CA125 values) were available in 1108 of these patients. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The results were then compared with previously published data from a large Australian gynecological cancer center (GCC, n = 204). RESULTS: With the use of an RMI cutoff of 200, malignant ovarian tumors were correctly triaged to a gynecologic oncologist in 123 of 172 cases, leading to a sensitivity of 72% and specificity of 92% in our general outpatient clinic population compared with a sensitivity of 84% and a specificity of 77% in the GCC high-risk population. The negative predictive value was 95% compared with only 85% in the GCC cohort. We hypothesize that improvement of the overall detection rate of malignancy could be improved from 72% to 85% using a 2-step model, referring patients with an ultrasonic score of 3 to an experienced sonographer who uses pattern recognition. CONCLUSIONS: The RMI is an easy and reliable tool for the accurate triage of adnexal masses. Its value is higher in an unselected gynecological outpatient setting. Our proposed 2-step model including expert pattern recognition could influence particularly the detection rate in borderline and early-stage ovarian cancers and overcome the limitations of the tumor marker CA125.

Changing patterns of referrals and outcomes of genetic participation in gynaecological-oncology multidisciplinary care.

BACKGROUND: Genetic participation in gynaecological oncology multidisciplinary team meetings (MDT) may identify the sentinel cancer in women with hereditary breast-ovarian cancer syndrome or Lynch syndrome. AIMS: To identify the changing patterns of genetic referral from 2010 to 2014 and the outcomes of referrals through clinical MDT case review. MATERIALS AND METHODS: Medical records of cases of gynaecological cancer presented at the MDT meetings and genetics databases were reviewed to determine the frequency and outcomes of recommendations for genetic referral between 2010 and 2014. RESULTS: Four hundred and sixty-two women of 2523 cases reviewed were recommended for referral, increasing from 8% in 2010 to 25% in 2014. However, 167 of 462 patients (36%) had not registered with a Hereditary Cancer Clinic in NSW/ACT, including 11 women with high-grade serous ovarian cancer and seven women with abnormal MMR immunohistochemistry. Mutations were identified in 40 of 165 women (24%) undergoing breast cancer BRCA1/2 testing and in ten of 25 women (40%) who underwent MMR genetic testing. Eighty-one first- or second-degree relatives of these women have undergone predictive testing, identifying 48 mutation carriers and 33 non-carriers. CONCLUSION: Changing indications and increased participation by a genetic consultant in the weekly MDT meeting has led to increasing genetic referrals over the last five years. Follow up of referrals needs to be addressed. With decreasing costs of genetic testing and use of readily transportable DNA collected through saliva or mouth swabs, we propose that distance should not be a barrier to this model being extended to all centres providing care to gynaecological cancer patients.

Changing Trends in Vulvar Cancer Incidence and Mortality Rates in Australia Since 1982.

BACKGROUND: The objective of this study was to assess trends in vulvar cancer incidence and mortality in Australia. METHODS: Case numbers for invasive carcinoma of the vulva (1982-2009) and vulvar cancer deaths (1982-2011) were obtained from the National Cancer Statistics database. Standardized rate ratios (SRRs) were used to assess changes in age-standardized incidence and mortality rates, for all ages and for younger than 60 years and 60+ years. RESULTS: Age-standardized incidence rates in women across all ages did not significantly change from 1982-1984 to 2007-2009 (from 2.1 to 2.5 per 100,000 women; SRR from the later to the earlier period, 1.13 [95% CI, 1.00-1.27]). However, there was a significant 84% increase in incidence in women younger than 60 years (SRR, 1.84 [95% CI, 1.49-2.26]), with no change for women 60+ years (SRR, 0.90 [95% CI, 0.79-1.04]). Age-standardized mortality in women across all ages significantly decreased by 22% from 1982-1986 to 2007-2011 (from 0.7 to 0.5 per 100,000 women; SRR, 0.78 [95% CI, 0.66-0.93]). However, this was driven by declines in older women, with stable rates in women younger than 60 years (SRR, 1.05 [95% CI, 0.62-1.79]); rates in 60+ years decreased by 24% (SRR, 0.76 [95% CI, 0.63-0.91]). CONCLUSION: Since the early 1980s, vulvar cancer incidence has increased by more than 80% in women younger than 60 years in Australia, but there has been no increased incidence in older women. These findings are consistent with the possibility of increased exposure to the human papillomavirus in cohorts born after 1950. By contrast, age-standardized vulvar cancer mortality rates have been stable in younger women, but have declined in older women.

Methylation-capture and Next-Generation Sequencing of free circulating DNA from human plasma.

BACKGROUND: Free circulating DNA (fcDNA) has many potential clinical applications, due to the non-invasive way in which it is collected. However, because of the low concentration of fcDNA in blood, genome-wide analysis carries many technical challenges that must be overcome before fcDNA studies can reach their full potential. There are currently no definitive standards for fcDNA collection, processing and whole-genome sequencing. We report novel detailed methodology for the capture of high-quality methylated fcDNA, library preparation and downstream genome-wide Next-Generation Sequencing. We also describe the effects of sample storage, processing and scaling on fcDNA recovery and quality. RESULTS: Use of serum versus plasma, and storage of blood prior to separation resulted in genomic DNA contamination, likely due to leukocyte lysis. Methylated fcDNA fragments were isolated from 5 donors using a methyl-binding protein-based protocol and appear as a discrete band of ~180 bases. This discrete band allows minimal sample loss at the size restriction step in library preparation for Next-Generation Sequencing, allowing for high-quality sequencing from minimal amounts of fcDNA. Following sequencing, we obtained 37 × 10(6)-86 × 10(6) unique mappable reads, representing more than 50% of total mappable reads. The methylation status of 9 genomic regions as determined by DNA capture and sequencing was independently validated by clonal bisulphite sequencing. CONCLUSIONS: Our optimized methods provide high-quality methylated fcDNA suitable for whole-genome sequencing, and allow good library complexity and accurate sequencing, despite using less than half of the recommended minimum input DNA.

ZNF300P1 encodes a lincRNA that regulates cell polarity and is epigenetically silenced in type II epithelial ovarian cancer.

BACKGROUND: We previously identified that the CpG island-associated promoter of the novel lincRNA ZNF300P1 (also known as LOC134466) is frequently hypermethylated and silenced in ovarian cancer tissues. However, the function of ZNF300P1 was unknown. In this report we demonstrate that ZNF300P1 is involved in the regulation of key cell cycle and cell motility networks in human ovarian surface epithelial cells, and may play a role in promoting metastasis in ovarian cancer cells. METHODS: We applied methylated DNA immunoprecipitation on whole genome promoter tiling arrays and Sequenom assays to examine methylation status of ZNF300P1 in multiple ovarian cancer cell lines, as well as in normal ovarian and ovarian tumor tissues. Transcript profiling was used to investigate the effects of ZNF300P1 suppression in ovarian cancer cells. We utilized siRNA knockdown in normal ovarian surface epithelial cells and performed cellular proliferation, migration and adhesion assays to validate and explore the profiling results. RESULTS: We demonstrate that ZNF300P1 is methylated in multiple ovarian cancer cell lines. Loss of ZNF300P1 results in decreased cell proliferation and colony formation. In addition, knockdown of the ZNF300P1 transcript results in aberrant and less persistent migration in wound healing assays due to a loss of cellular polarity. Using an ex vivo peritoneal adhesion assay, we also reveal a role for ZNF300P1 in the attachment of ovarian cancer cells to peritoneal membranes, indicating a potential function of ZNF300P1 expression in metastasis of ovarian cancer cells to sites within the peritoneal cavity. CONCLUSION: Our findings further support ZNF300P1 as frequently methylated in ovarian cancer and reveal a novel function for ZNF300P1 lincRNA expression in regulating cell polarity, motility, and adhesion and loss of expression may contribute to the metastatic potential of ovarian cancer cells.

Expression of GBGT1 is epigenetically regulated by DNA methylation in ovarian cancer cells.

BACKGROUND: The GBGT1 gene encodes the globoside alpha-1,3-N-acetylgalactosaminyltransferase 1. This enzyme catalyzes the last step in the multi-step biosynthesis of the Forssman (Fs) antigen, a pentaglycosyl ceramide of the globo series glycosphingolipids. While differential GBGT1 mRNA expression has been observed in a variety of human tissues being highest in placenta and ovary, the expression of GBGT1 and the genes encoding the glycosyltransferases and glycosidases involved in the biosynthesis of Fs as well as the possible involvement of DNA methylation in transcriptional regulation of GBGT1 expression have not yet been investigated. RESULTS: RT-qPCR profiling showed high GBGT1 expression in normal ovary surface epithelial (HOSE) cell lines and low GBGT1 expression in all (e.g. A2780, SKOV3) except one (OVCAR3) investigated ovarian cancer cell lines, a finding that was confirmed by Western blot analysis. Hierarchical cluster analysis showed that GBGT1 was even the most variably expressed gene of Fs biosynthesis-relevant glycogenes and among the investigated cell lines, whereas NAGA which encodes the alpha-N-acetylgalactosaminidase hydrolyzing Fs was not differentially expressed. Bisulfite- and COBRA-analysis of the CpG island methylation status in the GBGT1 promoter region demonstrated high or intermediate levels of GBGT1 DNA methylation in all ovarian cancer cell lines (except for OVCAR3) but marginal levels of DNA methylation in the two HOSE cell lines. The extent of DNA methylation inversely correlated with GBGT1 mRNA and protein expression. Bioinformatic analysis of GBGT1 in The Cancer Genome Atlas ovarian cancer dataset demonstrated that this inverse correlation was also found in primary ovarian cancer tissue samples confirming our cell line-based findings. Restoration of GBGT1 mRNA and protein expression in low GBGT1-expressing A2780 cells was achieved by 5-aza-2'-deoxycytidine treatment and these treated cells exhibited increased helix pomatia agglutinin-staining, reflecting the elevated presence of Fs disaccharide on these cells. CONCLUSIONS: GBGT1 expression is epigenetically silenced through promoter hypermethylation in ovarian cancer. Our findings not only suggest an involvement of DNA methylation in the synthesis of Fs antigen but may also explain earlier studies showing differential GBGT1 expression in various human tissue samples and disease stages.

Quality of life after complete lymphadenectomy for vulvar cancer: do women prefer sentinel lymph node biopsy?

OBJECTIVES: Leg lymphoedema occurs in up to 60% of women after a complete inguinal-femoral lymphadenectomy for vulvar cancer. To avoid lymphoedema, sentinel lymph node biopsy has become the preferred method of staging. However, false-negative results may influence survival, making the sentinel node procedure unacceptable to many fully informed women. The aims of this study were to measure the quality of life (QoL) in women after a complete lymphadenectomy for vulvar cancer and to quantify the risk to survival these women would be prepared to take with sentinel node biopsy. MATERIALS AND METHODS: Sixty women who had a complete lymphadenectomy for early-stage vulvar cancer participated in structured interviews. The severity of lymphoedema symptoms was recorded. The QoL-adjusted survival was measured using the Utility-Based Questionnaire-Cancer, a cancer-specific validated QoL instrument. The women stated their preference for sentinel node biopsy or complete lymphadenectomy. A "standard-gamble" preference table was used to quantify the degree of risk to survival they would take to avoid lymphoedema. RESULTS: Seventy-three percent of women reported lymphoedema after complete lymphadenectomy. Women with lymphoedema or leg pain had significantly worse scores for QoL in terms of social activity as well as physical and sexual function. Overall, 80% of women would choose complete lymphadenectomy rather than sentinel node biopsy if the risk of missing a positive lymph node was higher than 1 in 100, but if the risk of missing a positive lymph node was lower than 1 in 100, almost one third of the women would prefer sentinel node biopsy. CONCLUSIONS: Although women treated for early-stage vulvar cancer report reduced QoL after complete lymphadenectomy, most would choose complete lymphadenectomy over sentinel node biopsy. However, there is an individual level of risk that each woman can define with regard to her preference for the sentinel node procedure. Women with early-stage vulvar cancer should be offered an informed choice between complete lymphadenectomy or sentinel node biopsy.

Effects of access to and treatment in specialist facilities on survival from epithelial ovarian cancer in Australian women: a data linkage study.

OBJECTIVE: The aim of this study was to determine whether the distance of residence from a Gynecological Oncology Service (GOS) was associated with a better survival from ovarian cancer. METHODS: We linked cancer registry records to hospital records for 3749 women with ovarian cancer diagnosed between 2000 and 2008 in New South Wales, Australia. Access to a GOS was measured in kilometers from a woman's geocoded address to the geocoded address of the closest public GOS hospital. Flexible parametric survival, Cox proportional hazards, and logistic regression models were fitted to examine whether better access to a GOS was associated with a better survival and whether extensive surgery was received for ovarian cancer after adjustment for patient, tumor, and treatment factors. RESULTS: Hazard of death from ovarian cancer was greater in women who were treated in a public general hospital than in women treated in a GOS hospital (hazards ratio, 0.77; 95% confidence interval [CI], 0.64-0.95), and greater in those who did not have extensive surgery than in those who did (hazards ratio, 0.47; 95% CI, 0.38-0.58). The further women with ovarian cancer lived from a public GOS hospital, the more likely they were to be treated in a public general hospital. Women were 19 times more likely (odds ratio, 19.40; 95% CI, 13.92-27.04) to be treated only in a general hospital when they lived 187 km or more from a public GOS hospital than women who lived within 5 km of one. CONCLUSIONS: Distance of residence from GOS hospitals in Australia is an important determinant of access to GOS hospitals. Treatment in a public or private GOS hospital and having surgery were the strongest predictors of survival from epithelial ovarian cancer. Research is required into the barriers to referral of patients with ovarian cancer for care in GOS hospitals; low population density limits options for supply of GOS in rural areas.

Sexuality and body image following treatment for early-stage vulvar cancer: a qualitative study.

AIM: To describe women's experiences of sexuality and body image following treatment for early-stage vulvar cancer. BACKGROUND: There is limited information available on sexual function following treatment for early-stage vulvar cancer. A review of the literature has shown a lack of qualitative investigation into this topic. This study was undertaken to address this deficiency and to add to the existing body of knowledge describing the psychosexual outcomes for these women. DESIGN: Qualitative interview study. METHODS: A qualitative approach based on interpretive phenomenology was used to interview a purposive sample of 10 women (mean age 58 years) who had previously been treated for an early-stage vulvar cancer. Interviews were conducted from June-October 2009. Data were generated from verbatim transcription of the semi-structured in-depth interviews. Thematic analysis of these data revealed themes that were common to the women's experiences of sexuality and body image. FINDINGS: Four themes were identified that described the structure of the experience. Only two of these themes, sexuality and body image, will be discussed in this paper. CONCLUSIONS: Findings from this study indicated that the majority of women experienced little to no long-term disruption to sexuality and body image following conservative treatment for early-stage vulvar cancer. Intimacy and relationship status were more closely linked to women's sexual satisfaction than physical arousal. Factors contributing to women experiencing negative emotions were radical vulvar excision, multiple vulvar procedures and/or the development of lymphoedema.

Data set for reporting of endometrial carcinomas: recommendations from the International Collaboration on Cancer Reporting (ICCR) between United Kingdom, United States, Canada, and Australasia.

The International Collaboration on Cancer Reporting is a quadripartite alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, and the Canadian Partnership Against Cancer. The International Collaboration on Cancer Reporting was formed with a view to reducing the global burden of cancer data set development and reduplication of the effort by different international institutions that commission, publish, and maintain standardized cancer-reporting data sets. The resultant standardization of cancer reporting would be expected to benefit not only those countries directly involved in the collaboration, but also others not in a position to develop their own data sets. The main objective of the International Collaboration on Cancer Reporting is to develop an evidence-based-reporting data set for each cancer site, and to this end, a project to develop data sets for prostate, endometrium, and lung cancers and malignant melanoma was piloted by the quadripartite group. This review describes the process of development of the endometrial cancer data set.

Groin Surveillance by Serial Ultrasonography Rather Than Sentinel Node Biopsy or Inguinofemoral Lymphadenectomy for Patients with Vulvar Cancer: A Pilot Study.

A pilot study was conducted to determine whether 3-monthly groin ultrasonography could eliminate groin dissection after a negative bilateral groin ultrasound in three groups of patients: (i) Those with a unifocal stage 1B squamous cell carcinoma of up to 20 mm in diameter. (ii) Those with an ipsilateral squamous cell carcinoma of any size which extended to within 1 cm either side of the midline. These patients underwent ipsilateral inguinofemoral lymphadenectomy and ultrasonic surveillance of the contralateral groin. (iii) Patients with multifocal invasive lesions with the largest individual focus 20 mm or less in diameter. Three additional patients were added because they either refused groin dissection or were considered unfit for surgery. All ultrasonically positive nodes were confirmed histologically. Thirty-two patients were entered, and no patients were lost to follow-up. Forty-three groins were followed. With a median follow-up of 37 months, three positive nodes (9.4%) were detected. One patient died of her recurrence (3.1%), and 39 groins (90.7%) were preserved. The overall sensitivity of ultrasonic surveillance was 100% (95% CI: 44-100%), with a specificity of 97% (95% CI: 83-99%) and a negative predictive value of 100% (95% CI: 88-100%). This pilot justifies a larger study on serial ultrasonography in lieu of groin dissection in selected patients with vulvar cancer.

Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer.

OBJECTIVE: Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer. METHODS: The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR. RESULTS: The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10-11.07), p=0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated. CONCLUSIONS: This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.