ABSTRACTS Abstracts of the 4th meeting of the European Hereditary Tumour Group, Barcelona, Spain, October 17–19th, 2019 Ó Springer Nature B.V. 2020 Characterisation of clinical and pathological features associated with isolated PMS2 loss in Lynch Syndrome associated colorectal cancer Aine Stakelum, E ´ anna Ryan, Peter Molony, Robert Geraghty, Sean Martin, Ann Hanly, Ronan O’Connell, Rory Kennelly, Kieran Sheahan, Des Winter Centre for Colorectal Disease, St Vincent’s Hospital, Dublin 4, Ireland Objectives Lynch syndrome is the commonest hereditary colorectal cancer syn- drome and results from a germline mutation in one of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. Universal screening of all incident CRCs for DNA mismatch repair deficiency (dMMR) is now recommended to identify patients with LS and guide surveillance and treatment options. This study aimed to characterise the clinical and pathological characteristics of a cohort of patients with isolated PMS2 loss. Methods Immunohistochemistry for dMMR was performed on all incident CRCs between 2006 and 2018. Data including patient demographics, clinical details, and histological tumour parameters, was extracted from original pathology reports with any missing information being repopulated by review of the original slides. Results 3095 colorectal cancers were resected over the 12-year study period and 328 of these displayed mismatch repair deficiency on immuno- histochemical staining. Of these, 16 patients (56% male) showed isolated PMS2 loss. Of those patients who accepted genetic testing, 88.9% had a germline mutation in the PMS2 gene. The majority (75%) presented with stage 2 disease with no patients having meta- static disease at diagnosis. Tumours showed a predilection for the right colon (69%) and exhibited a localised inflammatory response with more than half demonstrating a high Klintrup–Makinen score. Patients with isolated PMS2 loss had a favourable prognosis with no recurrences and a 5-year disease-free survival rate of 83%. Conclusions Isolated PMS2 loss is a rare presentation of Lynch Syndrome and is associated with favourable survival outcomes. Risk Reduction depends on the Level of Compliance with Surveillance for Colorectal Cancer in Lynch syndrome Lars Joachim Lindberg 1 , Maria Rasmussen 1 , Klaus Kaa Andersen 2 , Mef Nilbert 2,1,3 , Christina Therkildsen 1 1 Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark. 2 The Danish Cancer Society Research Centre, Copenhagen, Denmark. 3 Department of Oncology and Pathology, Lund University, Lund, Sweden Objectives Lynch syndrome confers an increased risk of colorectal cancer, which motivates colonoscopic surveillance programs to reduce morbidity and mortality. The effect from these surveillance programs depends on individual risk factors and levels of compliance, which vary during life and complicate risk modelling. We determined how different levels of compliance relates to individual factors and influences risk of colorectal cancer in the Danish Lynch syndrome cohort. Methods In a nationwide, prospective observational register study covering 1223 individuals, we estimated the risk of colorectal cancer and assessed clinicopathological data in relation to compliance. We developed a time-based model classifying time at-risk as fully, par- tially and non-compliant with recommended biennial colonoscopies and estimated the cumulative life-time risk and hazard rate ratios of first and metachronous colorectal cancer. Results During the study period, 99 first and 48 metachronous colorectal cancers developed. Compliance was associated with female gender, previous history of cancer and age \ 75 years. The risk of colorectal cancer was proportionally related to the level of compliance with cumulative incidences at age 75 of 38% (95% CI 27–50%) for full compliance, 48% (95% CI 29–67%) for partial compliance, and 72% (95% CI 61–83%) for non-compliance. Full compliance gave a 4-fold risk reduction (HR = 0.28), while partial compliance resulted in a 2-fold risk reduction (HR = 0.47) compared to non-compliance. Conclusions The colorectal cancer risk reduction gained from colonoscopic surveillance in Lynch syndrome is related to the level of compliance, which calls for motivational initiatives to optimize benefit. 123 Familial Cancer https://doi.org/10.1007/s10689-019-00150-8