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Master's Dissertation
DOI
10.11606/D.5.2017.tde-23082017-120645
Document
Author
Full name
Pâmela de Oliveira Soares
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Garcia, Maria Lucia Bueno (President)
Tibério, Iolanda de Fátima Lopes Calvo
Braga, Alfésio Luis Ferreira
Tavares, Marcos Roberto
Title in Portuguese
Expressão da glutationa S-transferase pi em pacientes com carcinoma epidermóide de cabeça e pescoço conforme os hábitos tabágico e etílico
Keywords in Portuguese
Alcoolismo
Carcinoma de células escamosas
Glutationa transferase
Hábito de fumar
Imuno-histoquímica
Neoplasias de cabeça e pescoço
Papillomaviridae
Abstract in Portuguese
O carcinoma epidermoide da cabeça e pescoço (CECP) tem alta prevalência mundial, alta morbimortalidade e impacto negativo na saúde individual e pública. Apresenta como principais fatores de risco o tabagismo, etilismo e infecção pelo Papilomavírus humano (HPV). A glutationa S-transferase pi (GSTPI) é uma enzima de detoxificação de carcinógenos com expressão aumentada em alguns tipos de câncer e parece associar-se a pior resposta terapêutica. Estudamos a expressão da GSTPI e a influência dos fatores de risco tabagismo, etilismo e HPV em amostras de tecido tumoral e margens não tumorais de portadores de CECP. Os dados foram obtidos do projeto temático Genoma do Câncer de Cabeça e Pescoço (GENCAPO). Os pacientes foram caracterizados: não tabagistas e não etilistas (NTNE) e tabagistas e etilistas (TE) e posteriormente pareados, perfazendo um total de 47 pares. O pareamento baseou-se em idade, sítio tumoral, estadiamento TNM, grau de diferenciação tumoral e variantes morfológicas. As amostras foram coradas por imuno-histoquímica para GSTPI e a presença de imunomarcação semiquantificada em escores de 0 a 3 (0: 0 a 10%; 1: de 10% a 30%; 2: de 31% a 60%: 3: para > 60%). Os dados foram analisados pelo teste de McNemar, Fisher, a sobrevida pela curva de Kaplan-Meier e teste de long rank. Houve expressão do biomarcador no tumor independente do hábito tabágico ou etílico. A expressão de GSTPI na margem do tumor foi maior no grupo TE (p=0,004). Não houve associação entre a marcação de GSTPI nas amostras de pacientes NTNE e TE em relação à positividade para HPV. Não houve óbitos no grupo NTNE com baixa imunomarcação no tumor, o que inviabilizou as análises de sobrevida neste grupo. Não houve diferença de sobrevida conforme a imunomarcação para GSTPI em margem de tumor (p=0.538). Este estudo demonstra que a marcação de GSTPI em CECP está presente no tumor independente do hábito. Na margem do tumor, os fatores de risco tabagismo e etilismo associam-se a maior presença do biomarcador, sugerindo o papel da GSTPI na tentativa de eliminação destas toxinas
Title in English
Expression of glutathione S-transferase pi in patients with squamous cell carcinoma of the head and neck as smoking habits and ethyl
Keywords in English
Alcoholism
Carcinoma squamous cell
Glutathione transferase
Head and neck neoplasms
Immunohistochemistry
Papillomaviradae
Smoking
Abstract in English
Head and neck squamous cell carcinoma (HNSCC) presents a high prevalence worldwide, high mortality and negative impact on individual and public health. Its main risk factors are tobacco, alcohol consumers and human papillomavirus infection (HPV). The pi glutathione S-transferase (GSTPI) is a carcinogen-detoxifying enzyme with increases expression in some kinds of cancer and it seems to worsen the therapy response. We studied the expression of GSTPI in tumors samples and the influence of risk factors; tobacco, alcohol and HPV. The data were obtained from Genome Head and Neck Cancer Thematic Project (GENCAPO). Patients were divided in two groups: non smokers and non drinkers (NSND) and smokers and drinkers (SD) and then selected in 47 pairs based on age, sex, tumor site, TNM staging, degree of tumor differentiation and morphological variants. Each pair was previously tested for HPV in GENCAPO project. Samples were stained by immunohistochemistry for GSTPI and analyzed by semi-quantitative method for scores from 0 to 3 according to immunostaning (0: 0 to 10%; 1: 10% to 30%; 2: 31% to 60% : 3: to > 60%). Data were analyzed using McNemar test, Fisher and for survival analysis by the Kaplan-Meier curve and long rank test. The biomarker expression in the tumor was present in both groups independently of smoking and drinking habits. The GSTPI expression in tumor margin was higher in SD group (p = 0.004). There was no association between GSTPI expression and positivity for HPV in both groups. There were no deaths in NSND group presenting low tumor GSTPI expression, which prevented the survival analysis in this group. The survival rate was similar in both groups according to GSTPI immunostaining in tumor margin (p = 0.538). This study showed that the GSTPI biomarker in HNSCC was present independently of the smoking and drinking habit or positivity to HPV. Tobacco and alcohol consumption were associated with greater biomarker expression in the tumor margin, suggesting that GSTPI may modulate the elimination of these toxins
 
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Publishing Date
2017-08-25
 
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