Thymidylate synthase expression in circulating tumor cells: A new tool to predict 5‐fluorouracil resistance in metastatic colorectal cancer patients |
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Authors: | Emne Ali Abdallah Marcello Ferretti Fanelli Marcilei Eliza Cavicchioli Buim Marcelo Calil Machado Netto José Luiz Gasparini Junior Virgílio Souza e Silva Aldo Lourenço Abbade Dettino Natalia Breve Mingues Juliana Valim Romero Luciana Menezes Mendonça Ocea Bruna Maria Malagoli Rocha Vanessa Silva Alves Daniel Vilarim Araújo Ludmilla Thomé Domingos Chinen |
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Institution: | 1. International Research Center, A. C. Camargo Cancer Center, S?o Paulo, Brazil;2. Department of Clinical Oncology, A. C. Camargo Cancer Center, S?o Paulo, Brazil;3. Department of Health, Universidade Nove De Julho, S?o Paulo, Brazil |
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Abstract: | Thymidylate synthase (TYMS) is an important enzyme for 5‐fluorouracil (5‐FU) metabolism in metastatic colorectal cancer (mCRC) patients. The search for this enzyme in circulating tumor cells (CTCs) can be a powerful tool to follow‐up cancer patients. mCRC patients were enrolled before the beginning of 5‐FU‐based chemotherapy. The blood was filtered on Isolation by Size of Epithelial Tumor Cells (ISET), and the analysis of TYMS expression in CTCs was made by immunocytochemistry. Additionally, we verified TYMS staining in primary tumors and metastases from the same patients. There were included 54 mCRC patients and 47 of them received 5‐FU‐based chemotherapy. The median CTCs number was 2 per mL. We were not able to analyze immunocytochemistry in 13 samples (9 patients with absence of CTCs and 4 samples due to technical reasons). Therefore, TYMS expression on CTCs was analyzed in 34 samples and was found positive in 9 (26.5%). Six of these patients had tumor progression after treatment with 5‐FU. We found an association between CTC TYMS staining and disease progression (DP), although without statistical significance (P = 0.07). TYMS staining in primary tumors and metastases tissues did not have any correlation with disease progression (P = 0.67 and P = 0.42 respectively). Patients who had CTC count above the median (2 CTCs/mL) showed more TYMS expression (P = 0.02) correlating with worse prognosis. Our results searching for TYMS staining in CTCs, primary tumors and metastases suggest that the analysis of TYMS can be useful tool as a 5‐FU resistance predictor biomarker if analyzed in CTCs from mCRC patients. |
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Keywords: | thymidylate synthase chemotherapy resistance metastatic colorectal cancer circulating tumor cells isolation by size of epithelial tumor cells |
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