Background Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS.Methods In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

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The introduction of genomic studies has enabled assessment of the clonality of synchronous tumours involving the ovary and other sites in the female genital tract in a definitive way. This has led to the abandonment of conventional approaches to primary site assignment, and the recognition that most such synchronous neoplasms are clonally related single tumours with metastatic spread, rather than independent primary tumours. These discoveries have implications for diagnostic practice, analogous to the gradual change over the last few decades in our approach to mucinous neoplasms of the ovary metastatic from the gastrointestinal tract. In this review, we first examine the routes of metastasis to the ovary, and then discuss the diagnostic and clinical implications of concurrent ovarian carcinomas arising in combination with endometrial, endocervical and tubal carcinomas. It is proposed that cases of primary low‐grade endometrioid endometrial carcinoma with a secondary unilateral ovarian tumour, both with indolent characteristics, may be classified as ‘FIGO stage IIIA‐simulating independent primary tumours’, with a comment that conservative management would be appropriate. It should be recognised that human papillomavirus‐associated endocervical adenocarcinomas may result in synchronous or metachronous ovarian metastases that appear to be unrelated to the primary tumour, and that these may be managed conservatively in the absence of other sites of disease. In cases of tubo‐ovarian high‐grade serous carcinoma, tubal intraepithelial or contralateral adnexal involvement should count as a pelvic disease site for staging purposes.

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Subclassification of endometrial carcinoma (EC) based on morphologic features alone has been shown to have suboptimal reproducibility, both in regard to biopsy versus hysterectomy findings, as well as interobserver agreement. This restricts the role of morphologic classification of EC as a tool for risk prediction and therefore treatment planning. A diagnostic algorithm based on The Cancer Genome Atlas (TCGA) classification of EC holds promise for improving accuracy in risk prediction. This classifies EC into 4 groups: those harbouring mutations in the exonuclease domain of DNA polymerase epsilon, POLE (POLEmut), those showing a mismatch repair defect, those showing mutations in TP53 (p53abn) and a heterogenous group showing none of these 3 abnormalities (currently termed no specific molecular profile). These groups can be accurately and reproducibly diagnosed on biopsy samples using a limited panel of tests, namely immunohistochemistry for mismatch repair proteins and p53, and testing for POLE exonuclease domain pathogenic variants. In this article we briefly review the biology, testing and interpretation of POLE and mismatch repair defects in EC.

Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and is largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neoadjuvant chemotherapy, with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy.

OR DECADES, the supply of qualified special educators has been critically low. In 1983, the shortage of special educators was highlighted in A Nation at Risk. It is still with us 25 years later and shows no signs of disappearing, and in the coming decades it could well worsen. Although the production of teachers in special education increased during the 1990s, the most recently available data indicate that just .86 teachers were prepared for each available position in special education, while more than twice as many teachers were produced for each available position in elementary educa-A Field at Risk: THE TEACHER SHORTAGE IN SPECIAL EDUCATION A shortage of special education teachers existed in 1983, and the problem persists today. The authors emphasize that there is a pressing need not only to recruit and retain qualified special education teachers but also to diversify the special education teaching force.