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BACKGROUND: 5-Fluorouracil (5-FU) is essential in treating gastrointestinal cancers, but some patients show severe toxicity. The toxicity is exposure-related, which is linked to the enzyme dihydropyrimidine dehydrogenase (DPD) decoded by the DPYD gene. This study aimed to evaluate the possible toxicity related to 5-FU plasma levels, DPYD genotyping, and DPD phenotyping. METHODS: Forty-seven gastrointestinal cancer patients receiving 5-FU were included in this study. 5-FU plasma levels and DPD phenotyping were analyzed by UPLC-MS/MS. DPYD genotyping was also assessed. The Common Terminology Criteria for Adverse Events (CTCAE) was used to classify the toxicity. RESULTS: For hematological toxicity, 27.65% showed neutropenia, 78.72% anemia, and 29.78% thrombocytopenia. The area under the curve (AUC) of 5-FU calculated from the plasma was evaluated for three treatment cycles, and we observed that at the initial cycle, 48.93% were underexposed and 10.63% were overexposed, with a total of 59.56% of patients outside the therapeutic range. In the DPYD genotyping, 97.87% of patients had a wild-type genotype, and 2.12% had c.1236G>A mutation (E412E, rs56038477). A total of 82.97% of patients showed a phenotype compatible with normal DPD activity. CONCLUSION: These findings suggest that the evaluation of DPYD genotyping and DPD phenotyping in the Brazilian population still requires further study. Moreover, the analysis of the plasma AUC of 5-FU could contribute to clinical routine, being a very useful tool, especially for identifying patients outside the therapeutic range and thus guiding more individualized doses, or even in the intervention of possible toxicities related to overexposure.
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BACKGROUND: Worldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis. OBJECTIVE: To investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location. METHODS: A cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y), as a primary antibody (Biocare Medical, USA). Standardized gastric adenocarcinoma's HER2 expression criteria has been used in the analysis of samples. RESULTS: There were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003). Regarding the anatomical site, HER2 was positive in only one (16.6%) of the six proximal cases and six (14.28%) of the 42 distal cases (P=0.88). CONCLUSION: HER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Lauren's intestinal subtype.
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Adenocarcinoma/metabolismo , Receptor ErbB-2/análise , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patologia , Idoso , Estudos Transversais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
Background Worldwide, gastric cancer is the fourth cancer in incidence and the second most common cause of cancer death. Gastric cancer is asymptomatic in the early stages and very often diagnosed at advanced stages, determining a dismal prognosis. Expression of the HER2 gene has been identified in about 20% of gastric cancer cases, and its hyper-expression is associated with poor prognosis. Objective To investigate HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship to the histological type and anatomic location. Methods A cross-sectional retrospective study analyzed the immunohistochemical expression of HER2 in a sample of 48 specimens of gastric cancer. Immunohistochemical analysis were performed using avidin-biotin-peroxidase method with C-erb B2 (clone EP1045Y), as a primary antibody (Biocare Medical, USA). Standardized gastric adenocarcinoma‘s HER2 expression criteria has been used in the analysis of samples. Results There were seven cases with reactivity for HER2. Five were of intestinal-type while two cases were of mixed-type in which the expression occurred in the intestinal component. It was identified a significant association of HER2 expression in the intestinal subtype of gastric adenocarcinoma (P=0.003). Regarding the anatomical site, HER2 was positive in only one (16.6%) of the six proximal cases and six (14.28%) of the 42 distal cases (P=0.88). Conclusion HER2 immunoexpression was identified in 14.6% of the samples, and the expression was significantly associated to Lauren’s intestinal subtype. .
Contexto O câncer gástrico ocupa o quarto lugar em incidência no mundo e é a segunda causa de óbito por neoplasia maligna. Por ser assintomático nas fases iniciais, na maioria das vezes, é diagnosticado em fases avançadas. A expressão do gene HER2 tem sido identificada em cerca de 20% dos casos de câncer gástrico e, sua hiper-expressão está associada a um pior prognóstico nestes pacientes. Objetivo Investigar a expressão imunoistoquímica do HER2 em espécimes de adenocarcinoma gástrico e sua relação com a classificação histológica e localização anatômica. Métodos Estudo transversal, retrospectivo, no qual foi analisada a expressão imunoistoquímica para o HER2, em uma amostra de 48 espécimes de câncer gástrico, através da técnica de imunoistoquímica, pelo método avidina-biotina-peroxidase utilizando anticorpo primário C-erb B2, clone EP1045Y (Biocare Medical, USA). Resultados Foram encontrados sete casos reativos para o HER2; destes, cinco eram casos de adenocarcinoma do tipo intestinal e dois eram casos do tipo misto, porém, nestes, a expressão ocorreu no componente intestinal, o que determinou uma associação significante da expressão de HER2 com o componente intestinal do adenocarcinoma gástrico (P=0,003). Em relação ao local anatômico, HER2 foi reativo em apenas um (16,6%) de seis casos proximais e seis (14,28%) dos 42 casos distais (P=0,88). Conclusão A expressão de HER2 ocorreu em 14,6% da amostra, associada significativamente ao subtipo intestinal de Lauren. .
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/metabolismo , /análise , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patologia , Estudos Transversais , Imuno-Histoquímica , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
AIM: To investigate the association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in southern Brazil. METHODS: We studied 189 esophageal samples from 125 patients from three different groups: (1) 102 biopsies from 51 patients with ESCC, with one sample from the tumor and another from normal esophageal mucosa distant from the tumor; (2) 50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma (HNSCC); and (3) 37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients, not exposed to smoking or alcohol consumption. Nested-polymerase chain reaction (PCR) with the MY09/11 and GP5/6 L1 primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks. All PCR reactions were performed with a positive control (cervicovaginal samples), with a negative control (Human Genomic DNA) and with a blank reaction containing all reagents except DNA. We took extreme care to prevent DNA contamination in sample collection, processing, and testing. RESULTS: The histological biopsies confirmed the diagnosis of ESCC in 52 samples (51 from ESCC group and 1 from the HNSCC group) and classified as well differentiated (12/52, 23.1%), moderately differentiated (27/52, 51.9%) or poorly differentiated (7/52, 13.5%). One hundred twenty-eight esophageal biopsies were considered normal (51 from the ESCC group, 42 from the HNSCC group and 35 from dyspeptic patients). Nine had esophagitis (7 from the HNSCC and 2 from dyspeptic patients). Of a total of 189 samples, only 6 samples had insufficient material for PCR analysis: 1 from mucosa distant from the tumor in a patient with ESCC, 3 from patients with HNSCC and 2 from patients without cancer. In 183 samples (96.8%) GAPDH, G3PDH and/or ß-globin were amplified, thus indicating the adequacy of the DNA in those samples. HPV DNA was negative in all the 183 samples tested: 52 with ESCC, 9 with esophagitis and 122 with normal esophageal mucosa. CONCLUSION: There was no evidence of HPV infection in different ESCC from southern Brazil.
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Carcinoma de Células Escamosas/virologia , DNA Viral/análise , Neoplasias Esofágicas/virologia , Testes de DNA para Papilomavírus Humano , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Brasil/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Fatores de Risco , Adulto JovemRESUMO
INTRODUÇÃO: Embora decrescendo nos países do chamado primeiro mundo, o adenocarcinoma gástrico mantém-se como terceiro tumor mais frequente no sexo masculino mundialmente. Sua mortalidade é muito elevada, fruto do diagnóstico tardio em lesões muito avançadas, o que frequentemente torna paliativo seu tratamento, motivos pelos quais se justificam estudos no sentido de melhorar estes resultados. MÉTODO: Revisão da literatura através do portal de periódicos da CAPES indicados por busca no sites da Bireme e PubMed. Além disso, foram consultados os sumários do 8º Congresso Internacional de Câncer Gástrico em 2009. Foi apresentada uma sugestão de algoritmo de atendimento destes pacientes. CONCLUSÕES: O surgimento de novas drogas anticancer, mais efetivas, está propiciando novas alternativas para a ressecção gástrica como tratamento paliativo. Novos protocolos estão surgindo mostrando boas perspectivas para melhorar os resultados desta doença.
INTRODUCTION: Although decreasing in the well developed countries, gastric adenocarcinoma still represents the third most common cancer in males worldwide. Its mortality is very high because of the lateness of its diagnosis over advanced lesions, which turns palliative its treatment in the majority of the cases. METHOD: Literature review using CAPES, PubMed and Bireme sites as well as the abstracts of the 8 º International Gastric Cancer Congress which was held in Krakow in 2009. CONCLUSIONS: The release of new anticancer drugs against gastric cancer is providing a revival of gastrectomy as an effective palliative treatment of advanced gastric cancer. New protocols are being published, showing better results in the treatment of this disease.