RESUMO
OBJECTIVES: The diagnostic performance of cytology in esophageal squamous cell carcinoma (ESCC) is meticulously described. METHODS: Cytological and biopsy specimens were prospectively taken during esophagogastroduodenoscopy of 123 individuals in 2013 and 2014. Cytology samples were maintained in preservative fluid until processing and biopsies were formalin-fixed and paraffin-embedded. RESULTS: Based on endoscopic biopsy results, 70 cases were positive for ESCC whilst 53 were negative for cancer. In addition, brush cytology showed high sensitivity and specificity (98.57 and 96.23%, respectively) in detecting the disease, and high accuracy (97.5%) comparable to that provided by histopathology which is the accepted gold standard. CONCLUSION: Brush cytology specimens preserved in liquid medium may be a good alternative for ESCC diagnosis.
Assuntos
Biópsia/métodos , Citodiagnóstico/métodos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esôfago/patologia , Estudos Transversais , Técnicas Citológicas/métodos , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Conservantes Farmacêuticos , Estudos Prospectivos , Sensibilidade e Especificidade , Preservação de Tecido/métodosRESUMO
Gastrointestinal stromal tumors (GISTs) owe their development to the activating mutations in mast/stem cell growth factor receptor (KIT) or platelet-derived growth factor receptor A (PDGFRA) oncogenes. Both these KIT and PDGFRA oncogenes are members of the type III transmembrane receptor tyrosine kinase family that stimulates intracellular signaling pathways controlling cell proliferation, adhesion, apoptosis, survival, and differentiation. The presence and type of KIT/PDGFRA mutations help to predict the imatinib mesylate therapy, a selective tyrosine kinase inhibitor. Moreover, there is reported a small proportion of wild-type GISTs for both KIT and PDGFRA genes, and tumors more often acquire secondary mutations on KIT, that results into imatinib resistance. New patents to the GISTs imatinib resistant have recently been introduced. At present, sunitinib, is prescribed as second line therapy for patients with imatinibresistant or imatinib-intolerant GIST, and a number of other drugs, such as masitinib and valatinib, are in the pipeline. The present research focuses on GISTs diagnostic, prognostic and therapeutic biomarkers and addresses the development of novel patents for the treatment of these patients.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Desenho de Fármacos , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/terapia , Animais , Antineoplásicos/química , Biomarcadores Tumorais/genética , Tumores do Estroma Gastrointestinal/genética , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Testes Genéticos , Humanos , Terapia de Alvo Molecular , Patentes como Assunto , Valor Preditivo dos Testes , Transdução de Sinais/efeitos dos fármacosRESUMO
Esophageal cancer (EC) is among the 10 most common and fatal malignacies in the world, presenting a marked geographic variation in incidence rates between and within different countries. The TP53 tumor suppressor gene is highly mutated in esophageal tumors and its mutation pattern can offer clues to the etiopathology of the tumor. As Brazil presents one of the highest incidence areas in the West, a deeper knowledge of the molecular mechanisms related to EC development in the Brazilian population is needed. We analyzed the mutation profile of 110 esophageal squamous cell carcinomas (ESCC) of patients from Southeastern Brazil (Rio de Janeiro and São Paulo) and collected data regarding alcohol intake and tobacco smoking. We detected 41 mutations in tumor samples from 38 patients. There was no association between mutation frequency and tobacco smoking or alcohol drinking. The most frequently mutated codons were 179, 214, 220 and 248. Codons 179, 220 and 248 are hot-spots for ESCC, but codon 214 presents only 0.7% of the mutations registered in the IARC database. The mutation profile revealed a high percentage of mutations at A:T base pairs (34.1%) followed by deletions (17.1%). We concluded that the mutation profile detected in this study is different from that of patients from Southern Brazil but very similar to that previously seen in French patients, being characterized by a high frequency of mutations at A:T base pairs, which may be associated with acetaldehyde, the metabolic product of ethanol.
Assuntos
Carcinoma de Células Escamosas/genética , Genes p53 , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Brasil/epidemiologia , Neoplasias Esofágicas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , FumarRESUMO
PURPOSE: The aim of this study was to investigate whether mRNA expression of the apoptosis-associated genes, XAF1 and XIAP, in bladder cancer patients correlates with response to neoadjuvant treatment. METHODS: Gene expression was analyzed by a real-time quantitative PCR method in paired samples from 14 bladder cancer patients treated with a combination of neoadjuvant gemcitabine and cisplatin. The prognostic significance of XAF1 and XIAP mRNA expression as well as the correlation with several clinical and pathological findings were evaluated. RESULTS: The clinical response in the XAF1-high subset (n = 5) was remarkably higher compared with the XAF1-low subset (n = 9) (100% vs. 44.4%; P = 0.038). These results translated into a notably improvement of progression-free survival (PFS) in the XAF1-high subset (log-rank P = 0.012). In addition, patients in the XAF1-high subset had a 3.9-fold decreased chance of dying from the disease (hazard ratio for death (HR), 0.257; (CI 95%), 0.043-1.536, P = 0.036). When we evaluated the expression of XIAP, although an inverse correlation was found between expression and pathological response, there were no statistically significant associations with the clinical response, the length of PFS, and OS. CONCLUSIONS: This is one of the few studies to address the role of XAF1 in a clinical setting. The data presented here identify XAF1 as a novel predictive and prognostic factor in bladder cancer patients. Furthermore, our observations are in line with previous studies, which point towards XAF1 as a tumor-suppressor gene. Nonetheless, additional studies, both mechanistic and translational, are warranted and may help not only in corroborating the role of XAF1 as a prognostic marker, but also as a potential target for anticancer therapy.