RESUMO
Circulating tumor cells are important markers of tumor progression and can reflect tumor behavior in metastatic colorectal cancer (mCRC). Identification of proteins that confer resistance to treatment is an important step to predict response and better selection of treatment for patients. Multidrug resistance-associated protein 1 (MRP1) and Multidrug resistance-associated protein 4 (MRP4) play a role in irinotecan-resistance, and Excision Repair Cross-Complementation group 1 (ERCC1) expression can confer resistance to platinum compounds. Here, we included 34 patients with mCRC and most of them received FOLFIRI or FOLFOX chemotherapy (91.1%). CTCs were isolated by ISET(®) Technology and identified in 30 patients (88.2%), with a median of 2.0 CTCs/mL (0-31.0). We analyzed the immunocytochemical expression of MRP1, MRP4 and ERCC1 only in patients who had previously detectable CTCs, accordingly to treatment received (n = 19, 15 and 13 patients, respectively). Among patients treated with irinotecan-based chemotherapy, 4 out of 19 cases with MRP1 positive CTCs showed a worse progression free survival (PFS) in comparison to those with MRP1 negative CTCs (2.1 months vs. 9.1 months; p = 0.003). None of the other proteins studied in CTCs had significant association with PFS. We analyzed also histological sections of primary tumors and metastases by immunohistochemistry, and found no association with clinicopathological characteristics or with PFS. Our results show MRP1 as a potential biomarker of resistance to treatment with irinotecan when found in CTCs from mCRC patients. This is a small proof-of-principle study and these early findings need to be validated in a larger cohort of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Gradação de Tumores , Metástase Neoplásica , Projetos Piloto , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: Thyroid nodules are the most common surgical disease of the thyroid. Fine-needle aspiration biopsy (FNAB) is the most commonly employed tool for establishing a diagnosis. However, 15% to 25% of FNAB reports yield inconclusive results. Immunostaining of cytological smears from FNAB with galectin-3 has been proposed as a tool for differentiating between benign and malignant nodules. We performed a systematic review to evaluate the utility of galectin-3. METHODS: Prospective studies of nodules with FNAB reports of "follicular neoplasm" and with a definitive diagnosis confirmed by histopathology were selected. Calculations of individual sensitivity, specificity, and positive and negative likelihood ratios were made. RESULTS: The articles selected were those with the best methodological quality. CONCLUSION: Galectin-3 could be a good tool to guide therapeutic decision in patients with thyroid nodules and FNAB results of follicular neoplasm, but available information has methodological flaws that precludes a definitive answer about galectin-3 utility in the clinical setting.