Mismatch repair system in colorectal cancer. Frequency, cancer phenotype, and follow-up.

INTRODUCTION AND AIMS: A frequent task in the study of colorectal carcinomas (CRC) is to identify tumors harboring deficient DNA mismatch repair systems (dMMR), which are associated with microsatellite instability. Given that there is scant information on those tumors in Mexican patients, our aim was to describe their frequency, clinical and pathologic characteristics, and results, which are necessary for future trials. MATERIALS AND METHODS: A consecutive series of CRC patients, treated and followed at a tertiary care center was performed. The clinical and pathologic variables and the risk of hereditary or familial cancer syndrome were retrieved. The original slides and hMLH1, hPMS2, hMSH2, hMSH6 immunohistochemistry were evaluated. Tumors with an absence of at least one protein were considered dMMR. Differences were contrasted, utilizing non-parametric tests. RESULTS: One hundred and forty-four patients were included, with a median age of 65 years. A total of 134/93% patients presented with sporadic CRC, 8/5.6% had a family history of CRC, and 2/1.4% met the diagnostic criteria for hereditary non-polyposis colon cancer, according to the Amsterdam and Bethesda criteria. dMMR tumors were found in 39 patients, distributed among the three groups. They were locally advanced (p<0.001), right-sided, had the mucinous phenotype, and harbored a Crohn's-like lymphoid reaction (all three features, p<0.04). Adjuvant or palliative chemotherapy was administered to 57 (39.6%), concomitant chemoradiotherapy to 24 (16.7%), but 63 (43.8%) patients received no additional treatment to surgery. Five-year follow-up was completed in 131 of the patients and the outcomes alive-with-disease or died-of-disease were more frequently observed in the proficient (pMMR) lesions. CONCLUSIONS: In the present pre-FOLFOX case series, outcomes were better in dMMR CRC than in proficient lesions.

Active haematological manifestations of systemic lupus erythematosus lupus are associated with a high rate of in-hospital mortality.

The aim of this study was to estimate the impact of the haematological manifestations of systemic lupus erythematosus (SLE) on mortality in hospitalized patients. For that purpose a case-control study of hospitalized patients in a medical referral centre from January 2009 to December 2014 was performed. For analysis, patients hospitalized for any haematological activity of SLE ( n = 103) were compared with patients hospitalized for other manifestations of SLE activity or complications of treatment ( n = 206). Taking as a variable outcome hospital death, an analysis of potential associated factors was performed. The most common haematological manifestation was thrombocytopenia (63.1%), followed by haemolytic anaemia (30%) and neutropenia (25.2%). In the group of haematological manifestations, 17 (16.5%) deaths were observed compared to 10 (4.8%) deaths in the control group ( P < 0.001). The causes of death were similar in both groups. In the analysis of the variables, it was found that only haematological manifestations were associated with intra-hospital death (odds ratio 3.87, 95% confidence interval 1.8-88, P < 0.001). Our study suggests that apparently any manifestation of haematological activity of SLE is associated with poor prognosis and contributes to increased hospital mortality.

The ACTN3 R577X polymorphism is associated with inflammatory myopathies in a Mexican population.

BACKGROUND: The ACTN3 gene encodes the fast muscle protein α-actinin-3. The ACTN3 R577X polymorphism is a premature stop codon and results in absence of α-actinin-3 in 577XX homozygotes. The aim of this study was to determine the ACTN3 genotype in idiopathic inflammatory myopathies (IIMs). METHODS: We performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis and recruitment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was analysed. RESULTS: A total of 36% of healthy subjects had the ACTN3 577XX polymorphism (α-actinin-3 deficiency), 18% had the 577RR (homozygous wild type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41% and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to increase the risk of developing IIM, and DM in particular, although this was not related to severity of expression of the phenotype. CONCLUSIONS: The ACTN3 577X allele appeared to increase the risk of developing IIM; 70% of IIM patients were deficient in α-actinin-3. By contrast, ACTN3 577XX patients seemed to have less severe disease as reflected in lower muscle enzyme levels.