Detection of circulating tumor cells and their correlation with tumor clinical evolution

• Grant number: 12/01273-8
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2012
• End date: May 31, 2014
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fernando Augusto Soares
• Grantee: Fernando Augusto Soares
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated researchers: Ludmilla Thomé Domingos Chinen

Abstract

The spread of cancer requires the presence of circulating tumor cells (CTCs), rare cells that are surrounded by billions of hematopoietic cells. More sensitive immunohistochemical and molecular assays have been developed for detection of CTCs. Deng et al. (2008) developed a method for displaying slides that combines the use of fluorescent antibody analysis of cell morphology observed under an optical microscope for the identification of CTCs. This method was applied to Ariol, an automated system of capture and image analysis. Through this system compared with the CellSearch System, approved by the FDA, these authors showed that Ariol was more sensitive, more accurate and better able to reproduce the results. ISET (Isolation by Size of Epithelial Tumor Cells) is a direct method of enrichment of epithelial cells by filtration. It is based on the observation that peripheral blood leukocytes are the smallest cells of the body, with a size ranging from 8 to 11 micrometers. Thus, these cells can be eliminated by filtering the blood through a polycarbonate membrane with pores calibrated (8 microns). Once isolated, CTCs can be assessed by Giemsa, hematoxylin-eosin or characterized by immunocytochemistry, FISH, TUNEL or microdissected for molecular analysis. This method can be used to evaluate the drug resistance genes. There are some studies showing a correlation between expression of genes for resistance / sensitivity to drugs and response to therapy, but rare studies show expression in CTCs and correlates with the expression in the tumor. The analysis of CTCs is not yet being used as part of routine to monitor patients eligible for relapse and / or recurrence or metastasis. Thus, it would be interesting to adopt a sensitive approach, capable of identifying CTCs. Coupled with its use in routine, analysis of CTCs initially in research, could help guide treatment, in some ways:- By the correlation between levels of CTCs and imaging, the clinician can know whether a given therapy is working or not;- Depending on the correlation found in this study, it may be possible to prevent the realization of many imaging tests, following up patients only by the levels of CTCs;- By observing the expression of markers / resistance genes in CTCs and its correlation with tumor expression and response, we can come to the conclusion that type of therapy is most effective for each patient. Also, if the expression of markers / resistance genes in CTCs correlate with tumor expression, one can see the possibility of response to a given treatment only by serological analysis, avoiding collecting and / or manipulation of tumor biopsy material. This is a prospective study, performed by collecting blood from patients with solid tumors metastatic or locally advanced (n = 230, CCR: 100 patients; pancreas: 30 patients, lung cancer: 100 patients) and will have as negative control, blood from healthy individuals and as a positive control, the same blood spiked with colon tumor cells maintained in culture. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

JOSÉ LUIZ GASPARINI-JUNIOR; MARCELLO FERRETTI FANELLI; EMNE ALI ABDALLAH; LUDMILLA THOMÉ DOMINGOS CHINEN. AVALIAÇÃO DA EXPRESSÃO DE MMP-2 E TGFß-RI EM CÉLULAS TUMORAIS CIRCULANTES DE PACIENTES COM CÂNCER DE PÂNCREAS E SUA CORRELAÇÃO COM EVOLUÇÃO CLÍNICA. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA-BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY, v. 32, n. 2, 2019-04-29. (12/01273-8)

DOMINGOS CHINEN, LUDMILLA T.; LOPES MELLO, CELSO A.; ABDALLAH, EMNE ALI; OCEA, LUCIANA M. M.; BUIM, MARCILEI E.; BREVE, NATALIA M.; GASPARINI JUNIOR, JOSE LUIZ; FANELLI, MARCELLO F.; PATERLINI-BRECHOT, PATRIZIA. Isolation, detection, and immunomorphological characterization of circulating tumor cells (CTCs) from patients with different types of sarcoma using isolation by size of tumor cells: a window on sarcoma-cell invasion. ONCOTARGETS AND THERAPY, v. 7, p. 1609-1617, 2014. (12/01273-8)

SOUZA E SILVA, VIRGILIO; DOMINGOS CHINEN, LUDMILLA THOME; ABDALLAH, EMNE A.; DAMASCENA, ALINE; PALUDO, JOCIANA; CHOJNIAK, RUBENS; ABBADE DETTINO, ALDO LOURENCO; LOPES DE MELLO, CELSO ABDON; ALVES, VANESSA S.; FANELLI, MARCELLO F.. Early detection of poor outcome in patients with metastatic colorectal cancer: tumor kinetics evaluated by circulating tumor cells. ONCOTARGETS AND THERAPY, v. 9, p. 7503-7513, 2016. (13/21730-7, 12/01273-8)

GASPARINI-JUNIOR, JOSE LUIZ; FANELLI, MARCELLO FERRETTI; ABDALLAH, EMNE ALI; DOMINGOS CHINEN, LUDMILLA THOME. EVALUATING MMP-2 AND TGF beta-RI EXPRESSION IN CIRCULATING TUMOR CELLS OF PANCREATIC CANCER PATIENTS AND THEIR CORRELATION WITH CLINICAL EVOLUTION. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA-BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY, v. 32, n. 2, 2019. (12/01273-8)

SOUZA E SILVA, VIRGILIO; ABDALLAH, EMNE ALI; CARVALHO DE BRITO, ANGELO BORSARELLI; BRAUN, ALEXCIA CAMILA; TARIKI, MILENA SHIZUE; LOPES DE MELLO, CELSO ABDON; CALSAVARA, VINICIUS FERNANDO; RIECHELMANN, RACHEL; DOMINGOS CHINEN, LUDMILLA THOME. Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer. DIAGNOSTICS, v. 11, n. 3, MAR 2021. (12/01273-8)