Luiz Sérgio Raposo

Salivary and serum proteomics in head and neck carcinomas: Before and after surgery and radiotherapy

Several body fluids have been evaluated as new sources for cancer biomarker discovery. In this context, salivary and serum proteomics seem promising diagnostic and predictive tools for head and neck diseases. In the present study, we performed a proteomic analysis of saliva and serum from patients presenting head and neck squamous cell carcinoma (HNSCC) and compared the results before and after therapy. In saliva of cancer patients, we observed an altered protein profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both proteins may contribute to control tumor growth and, therefore, represent targets for new analysis. We also detected serotransferrin and a modified transthyretin form with altered levels in serum from patients. Comparing preoperative and postreatment samples, the results showed that the protein profile after treatment reverted to a pattern closer to those observed for controls. These results add information on the role of secreted proteins in the cancer process and emphasize the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.

Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) gene and risk of Head and Neck Squamous Cell Carcinoma

UNLABELLED Methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism may be a risk factor for head and neck squamous cell carcinoma due to changes in folate levels that can induce disorders in the methylation pathway, which results in carcinogenesis. AIM To evaluate MTHFR C677T polymorphism in patients with head and neck squamous cell carcinoma and in individuals with no history of cancer, and to assess the association of this disease with clinical histopathological parameters. SERIES AND METHODS: A retrospective study that assessed gender, age, tobacco, alcohol consumption and clinical histopathological parameters in 200 patients (100 with disease and 100 with no history of cancer). PCR-RFLP molecular analysis was carried out and the chi-square test and multiple logistic regression were applied for the statistical analysis. RESULTS There was no association between MTHFR C677T polymorphism and head and neck cancer (p = 0.50). Significant differences between the study and control groups were observed at age over 50 years, tobacco use, and male gender (p <0.001). There was no association of disease with clinical-histopathological parameters. CONCLUSION No association between the MTHFR C677T polymorphism and head and neck squamous cell carcinoma was possible in this study.

5-Methyltetrahydrofolate-homocysteine methyltransferase gene polymorphism (MTR) and risk of head and neck cancer

The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC). The frequency of MTR A2756G (rs1805087) polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis) was used for comparisons between groups and multiple logistic regression (multivariate analysis) was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05), AG genotype (P = 0.019) and G allele (P = 0.028) may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008). The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.

Head and neck carcinogenesis: Impact of MTHFD1 G1958A polymorphism

OBJECTIVE To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to find the association of the polymorphism with the risk factors and clinical and histopathological characteristics. METHODS Retrospective study investigating MTHFD1 G1958A polymorphism in 694 subjects (240 patients in the Case Group and 454 in the Control Group) by Restriction Fragment Length Polymorphism (RFLP) Analysis. Multiple logistic regression and chi-square tests were used in the statistical analysis. RESULTS Multivariable analysis showed that smoking and age over 42 years were disease predictors (p < 0.05). MTHFD1 1958GA or AA genotypes were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more often found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03). CONCLUSION The presence of MTHFD1 G1948A polymorphism associated with smoking and alcoholism raises the head and neck cancer risk.

Carcinogênese de cabeça e pescoço: impacto do polimorfismo MTHFD1 G1958A

OBJECTIVE: To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to find the association of the polymorphism with the risk factors and clinical and histopathological characteristics. METHODS: Retrospective study investigating MTHFD1 G1958A polymorphism in 694 subjects (240 patients in the Case Group and 454 in the Control Group) by Restriction Fragment Length Polymorphism (RFLP) Analysis. Multiple logistic regression and chi-square tests were used in the statistical analysis. RESULTS: Multivariable analysis showed that smoking and age over 42 years were disease predictors (p < 0.05). MTHFD1 1958GA or AA genotypes were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more often found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03). CONCLUSION: The presence of MTHFD1 G1948A polymorphism associated with smoking and alcoholism raises the head and neck cancer risk.

Multiple symmetrical lipomatosis (Madelung's disease) Lipomatose simétrica múltipla (doença de Madelung)

A male patient, 47 years old, white, without comorbidi-ties, alcoholic for 20 years, presented to this unit with a complaint of bulging in the bilateral supraclavicular region, painless, which had been progressively growing for the past five years.At physical examination, he showed good overall status, with bilateral supraclavicular mass of soft consistency, pain -less, measuring 10 × 6 cm to the left and 12 × 8 cm to the right (Fig. 1A). The computed tomography (CT) confirmed the presence of a symmetrical supraclavicular mass, whose density was compatible with fat (Fig. 1C). The mass was sur-gically removed, and the anatomopathological analysis of the specimen evidenced the presence of lipomatosis (Figs. 1D, 1E, 1F). To date, the patient has progressed well with-out recurrence, and outpatient follow-up has been main-tained (Fig. 1B).

Multiple symmetrical lipomatosis (Madelung’s disease)✰✰Please cite this article as: Ikumi-Shibasaki I, Ikuo-Shibasaki H, Nakamoto TS, Baccan FS, Raposo LS. Multiple symmetrical lipomatosis (Madelung's disease). Braz J Otorhinolaryngol. 2014;80:90–1.

A male patient, 47 years old, white, without comorbidi-ties, alcoholic for 20 years, presented to this unit with a complaint of bulging in the bilateral supraclavicular region, painless, which had been progressively growing for the past five years.At physical examination, he showed good overall status, with bilateral supraclavicular mass of soft consistency, pain -less, measuring 10 × 6 cm to the left and 12 × 8 cm to the right (Fig. 1A). The computed tomography (CT) confirmed the presence of a symmetrical supraclavicular mass, whose density was compatible with fat (Fig. 1C). The mass was sur-gically removed, and the anatomopathological analysis of the specimen evidenced the presence of lipomatosis (Figs. 1D, 1E, 1F). To date, the patient has progressed well with-out recurrence, and outpatient follow-up has been main-tained (Fig. 1B).

Lipomatose simétrica múltipla (doença de Madelung)

A male patient, 47 years old, white, without comorbidi-ties, alcoholic for 20 years, presented to this unit with a complaint of bulging in the bilateral supraclavicular region, painless, which had been progressively growing for the past five years.At physical examination, he showed good overall status, with bilateral supraclavicular mass of soft consistency, pain -less, measuring 10 × 6 cm to the left and 12 × 8 cm to the right (Fig. 1A). The computed tomography (CT) confirmed the presence of a symmetrical supraclavicular mass, whose density was compatible with fat (Fig. 1C). The mass was sur-gically removed, and the anatomopathological analysis of the specimen evidenced the presence of lipomatosis (Figs. 1D, 1E, 1F). To date, the patient has progressed well with-out recurrence, and outpatient follow-up has been main-tained (Fig. 1B).