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Background: Lynch syndrome (LS) is the most frequent genetically pre-disposed colorectal cancer (CRC) syndrome, accounting for 2–3% of all CRC cases. In Estonia, ~1000 new cases are diagnosed each year. This retroactive and prospective study aimed to estimate the prevalence of LS and describe disease-causing variants in mismatch repair (MMR) genes in a diagnostic setting and in the Estonian general population. Methods: LS data for the diagnostic cohort were gathered from 2012 to 2022 and data for the general population were acquired from the Estonian Biobank (EstBB). Furthermore, we conducted a pilot study to estimate the improvement of LS diagnostic yield by raising the age limit to >50 years for immunohistochemistry analysis of MMR genes. Results: We estimated LS live birth prevalence between 1930 and 2003 in Estonia at 1:8638 (95% CI: 1: 9859–7588). During the study period, we gathered 181 LS individuals. We saw almost a six-fold increase in case prevalence, probably deriving from better health awareness, improved diagnostic possibilities and the implementation of MMR IHC testing in a broader age group. Conclusion: The most common genes affected in the diagnostic and EstBB cohorts were MLH1 and PMS2 genes, respectively. The LS diagnosis mean age was 44.8 years for index cases and 36.8 years (p = 0.003) for family members. In the MMR IHC pilot study, 29% had LS.

Introduction Dupuytren’s contracture (DC) is a chronic fibroproliferative disease of the hand, which is characterized by uncontrolled proliferation of atypical myofibroblasts at the cellular level. We hypothesized that specific areas of the DC tissue are sustaining the cell proliferation and studied the potential molecular determinants that might contribute to the formation of such niches. Methods We studied the expression pattern of cell proliferation marker Ki67, phosphorylated AKT (Ak mouse strain thymoma) kinase, DC-associated growth factors (connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), insulin-like growth factor 2 (IGF-2)) and extracellular matrix components (laminins, fibronectin, collagen IV) in DC tissue and normal palmar fascia using immunofluorescence microscopy and quantitative real-time polymerase chain reaction (qPCR). Results We found that proliferative cells in the DC nodules were concentrated in the immediate vicinity of small blood vessels and localized predominantly in the myofibroblast layer. Correspondingly, the DC-associated blood vessels contained increased levels of phosphorylated AKT, a hallmark of activated growth factor signaling. When studying the expression of potential activators of AKT signaling we found that the expression of bFGF was confined to the endothelium of the small blood vessels, IGF-2 was present uniformly in the DC tissue and CTGF was expressed in the DC-associated sweat gland acini. In addition, the blood vessels in DC nodules contained increased amounts of laminins 511 and 521, which have been previously shown to promote the proliferation and stem cell properties of different cell types. Conclusions Based on our findings, we propose that in the DC-associated small blood vessels the presence of growth factors in combination with favorable extracellular matrix composition provide a supportive environment for sustained proliferation of myofibroblasts and thus the blood vessels play an important role in DC pathogenesis.