We examined the influence of MLH1 c.293G>A, MSH2 c.211 1 9C>G, MSH3 c.3133G>A and EXO1 c.1765G>A polymorphisms, involved in DNA mismatch repair (MMR), on head and neck (HN) squamous cell carcinoma (SCC) risk and prognosis. Aiming to identify genotypes, DNA from 450 HNSCC patients and 450 controls was analyzed by PCR-RFLP or real time PCR. MSH2 GG plus MSH3 GG (31.7% vs. 18.7%, p 5 0.003) genotypes were higher in laryngeal SCC (LSCC) patients than in controls. Carriers of the respective combined genotype were under a 3.69 (95% CI: 1.54-8.81)-fold increased risk of LSCC. Interactions of tobacco and tobacco plus all the above-mentioned polymorphisms on HNSCC and LSCC risk were also evident in study (p 5 0.001). At 60 months of follow-up, relapse-free survival (RFS) was shorter in patients with EXO1 GG genotype (54.8% vs. 61.1%, p 5 0.03) and overall survival (OS) was shorter in patients with MSH3 GG genotype (42.8% vs. 52.5%, p 5 0.02) compared to those with other genotypes, respectively. After multivariate Cox analysis, patients with EXO1 GG and MSH3 GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03-2.20, p 5 0.03) and OS (HR: 1.59, 95% CI: 1.19-2.13, P 5 0.002) than those with the remaining genotypes, respectively. Our data present, for the first time, evidence that inherited MLH1 c.-93G>A, MSH2 c.211 1 9C>G, MSH3 c.3133G>A, and EXO1 c.1765G>A abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes.Exposure to tobacco smoke is considered the most important etiological factor in the development of head and neck (HN) squamous cell carcinoma (SCC). 1 Carcinogens present in tobacco, such as benzo(a)pyrene, could bind to DNA from epithelial cells of the upper aerodigestive tract, forming covalent DNA adducts and inducing replication errors, which can be associated with HNSCC origin. 2,3 However, not all smokers develop HNSCC suggesting that individual genetic background may also participate in the tumor etiology. 4 DNA mismatch repair (MMR) pathway contributes to maintain genetic stability. 5 MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 3 (MSH3) and exonuclease 1 (EXO1) proteins play important roles in this process, recognizing DNA damage induced by carcinogens from tobacco, and enabling its excision. 6,7 The ability to promote DNA repair of damaged cells is variable in humans, since several DNA repair proteins, such as MLH1, MSH2, MSH3 and EXO1, are encoded by polymorphic genes. 8,9 Variant alleles of MLH1 c.293G>A, 10 MSH2 c.211 1 9C>G 11 and EXO1 c.1765G>A 12 single nucleotide polymorphisms (SNPs) reduce the expression of encoded proteins when compared with the respective wild-type alleles, and have decrease in DNA repair as consequence. The role of MSH3 c.3133G>A in protein activity is not totally clarified. 13-15 GG genotype of MLH1 c.293G>A and variant allele A of EXO1 c.1765G>A SNP were associated with increased risk of oral SCC only in India 16 and Taiwan, 17 respectively. To the best of our knowledge, the roles of the ...

Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.

Neoadjuvant HT is a safe and feasible option, but it cannot be considered equivalent to CT. If neoadjuvant HT is performed, AIs are preferable over tamoxifen due to higher response rates.

Aneurismas de artéria femoral são raros, porém são o segundo tipo mais freqüente de aneurismas periféricos, sendo o aneurisma de artéria poplítea o mais comum. Normalmente, são de etiologia aterosclerótica. As complicações deste aneurisma são representadas por embolia, trombose e, mais raramente, a rotura. O objetivo deste trabalho é relatar um caso de um paciente com 59 anos, masculino, com queixa de dor súbita em membro inferior esquerdo associado à frialdade, palidez e ausência de pulsos. O ecocolordoppler evidenciou a presença de aneurisma trombosado da artéria femoral comum. O paciente foi submetido, com sucesso, à ressecção do aneurisma, com reconstrução do leito arterial.

Objective. This report is aimed at describing a rare clinical condition of advanced esophageal cancer with subcutaneous metastasis. Case Report. The present case refers to a patient diagnosed with stage IV esophageal squamous cell carcinoma which started with dysphonia and cervical nodules. Soon after that, the patient developed dysphagia and subcutaneous lesions on the right flank. Later in time, we documented a disease progression, with worsening of subcutaneous implants, lymph node, bone, and pulmonary metastases in addition to malignant hypercalcemia. Conclusion. This illustrates a rare presentation of an advanced esophageal neoplasm. Subcutaneous metastasis from internal malignancies is unusual, corresponding to less than 10% of cases. Its occurrence in patients with esophageal cancer is even less common with very few cases reported in literature.

Background Abnormalities in the intrinsic apoptosis pathway, associated with single nucleotide variants (SNVs) in caspase (CASP) genes, alter head and neck squamous cell carcinoma (HNSCC) proliferation and progression. This prospective study aimed to evaluate whether CASP9 c.‐1339A>G and CASP3 c.‐1191A>G SNVs influence the outcome of patients with HNSCC. Two hundred sixty‐two HNSCC patients were enrolled in the study. Methods DNA and RNA of peripheral blood samples were analyzed using real‐time polymerase chain reaction (PCR) for genotyping and quantitative PCR method for gene expression, respectively. Differences in CASP3 expressions were analyzed using the Mann‐Whitney test. Event‐free survival (EFS) and overall survival (OS) were calculated using the Kaplan‐Meier curves, log‐rank test, and Cox analyses. Results CASP3 c.‐1191AG or GG genotype was associated with higher CASP3 expression when compared with AA genotype (0.50 arbitrary units (AUs) ± 0.29 standard deviation (SD) vs 0.28 AUs ± 0.12 SD; P = .02). Patients with CASP9 c.‐1339GG genotype had 1.54 more chance of presenting disease progression or relapse than patients with CASP9 c.‐1339AA or AG genotype. Patients with CASP9 c.‐1339GG and CASP3 c.‐1191GG combined genotype had 2.64 more chance of presenting progression or relapse of the disease and 2.84 more chance of evolving to death than those with the remaining combined genotypes. Conclusions Our findings provide, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related to CASP9 c.‐1339A>G and CASP3 c.‐1191A>G SNVs, act as predictors of HNSCC patients' survival.

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