We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations, in 12 patients suspected of HNPCC. Three of the 12 also carried a mutation in MSH6.

The limited capacity to divide is one of the major differences between normal somatic cells and cancerous cells. This 'finite life span' of somatic cells is closely linked to loss of telomeric DNA at telomeres, the 'chromosome caps' consisting of repeated (7TAGGG) sequences., In more than 85% of advanced cancers, this telomeric attrition is compensated by telomerase, 'the immortality enzyme', implying that telomerase inhibition may restore mortality in tumor cells. This review discusses the progress in research on the structure and function of telomeres and the telomerase holoenzyme. In addition, new developments in telomere/telomerase targeting compounds such as antisense oligonucleotides and G-quadruplex stabilizing substances, but also new telomerase expression-related strategies such as telomerase promoter-driven suicide gene therapy and telomerase immunotherapy will be presented. It will be discussed how these data can be implemented in telomerase-directed therapies.

ObjectiveTo determine the efficacy of the addition of an ultrasound of the groins in routine follow up of women with vulvar squamous cell carcinoma (SCC) after a negative sentinel lymph node (SLN).DesignProspective single‐centre study.SettingA tertiary expert oncology centre for the treatment of vulvar cancer.PopulationAll women with vulvar SCC with a negative SLN, treated between 2006 and 2014.MethodsWe prospectively collected data of 139 women with vulvar SCC treated with an SLN procedure. We analysed data of 76 patients with a negative SLN. Three‐monthly follow‐up visits consisted of physical examination combined with an ultrasound of the groins by a radiologist.Main outcome measuresThe diagnostic value of ultrasound in the follow up of women with vulvar SCC with a negative SLN during the first 2 years after treatment.ResultsDuring a routine visit, two asymptomatic isolated groin recurrences were detected. Both patients were treated by inguinofemoral lymphadenectomy and adjuvant radiotherapy and are alive without evidence of disease 39 and 120 months after diagnosis. In total, 348 ultrasounds and 29 fine‐needle aspiration were performed. The sensitivity of ultrasound to detect a groin metastasis was 100% (95% CI 16–100%), and specificity was 92% (95% CI 89–95%).ConclusionsRoutine follow up including ultrasound of the groin led to early detection of asymptomatic isolated groin recurrences. Further research is necessary to determine the exact role of ultrasound in the follow up of patients with vulvar SCC with a negative SLN.Tweetable abstractRoutine follow up including ultrasound of the groin led to early detection of asymptomatic isolated groin recurrences.

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