DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil.

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.

Changes in the expression of matrix extracellular genes and TGFB family members in rotator cuff tears.

Lack of synthesis of extracellular matrix compounds may contribute to degeneration of the tendons. Thus, we aimed to evaluate the expression of extracellular matrix and TGFB family members in ruptured and non-ruptured tendons of the rotator cuff, as well as the effect of clinical factors on gene expression in tendon samples, and the relationship between histological findings and altered gene expression. Injured and non-injured supraspinatus tendon samples and subscapular non-injured tendon samples were collected from 38 patients with rotator cuff tears. Non-injured supraspinatus tendons were obtained from eight controls. Specimens were used for histological evaluation, quantification of collagen fibers, and mRNA and protein expression analyses. Increased COL1A1, COL1A2, COL3A1, COL5A1, FN1, TNC, and TGFBR1 mRNA expression was observed in the tear samples (p < 0.05). Duration of symptoms was correlated with the levels of collagen type I/III fibers (p = 0.032; ρ = 0.0447) and FN1 immunostaining (p = 0.031; ρ = 0.417). Smoking was associated with increased frequency of microcysts, myxoid degeneration, and COL5A1, FN1, TNC, and TGFB1 mRNA expression (p < 0.05). FN1 immunostaining was correlated with the number of years of smoking (p = 0.048; ρ = 0.384). Lower levels of collagen type I/III fibers were detected in samples with fissures (0 = 0.046). High frequency of microcysts was associated with increased COL5A1, FN1, and TNC expression (p < 0.05, for all comparisons). Neovascularization was associated with reduced FN1 (p = 0.035) and TGFBR1 expression (p = 0.034). Our findings show differential expression of matrix extracellular genes and TGFB family members in the degeneration process involved in rotator cuff tears. These molecular alterations are influenced by clinical factors. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2542-2553, 2018.