Abstract

Abstract Background: Whereas the pathological aspects of Gastric Adenocarcinomas (GAC) are well defined, there is still an important lack of biomarkers predictive of its occurrence, aggressiveness and response to neoadjuvant treatment. Nowadays, it is known that isolated or clustered Circulating Tumor Cells (respectively CTCs or CTMs, for Microemboli) can be found in the blood of patients many months before tumor detection. In this sense, the identification of CTCs/CTMs in GAC patients has a potential value as biomarkers for tumor growth and invasiveness. Objective: to study the predictive value of CTCs and CTMs from GAC patients, evaluating their presence and correlation with HER2-status and clinical-pathological characteristics. Methods: Blood was prospectively collected from 72 GAC patients (62.5% men) recruited at the Department of Abdominal Surgery of the A.C.Camargo Cancer Center, São Paulo, Brazil, from March 2016 to March 2017, after the signature of informed consent forms previously approved by the institutional review board. Blood was first collected before the first neoadjuvant cycle (at diagnosis) and also before adjuvant treatment (diagnosis of metastasis). The samples were processed and filtered in ISET (Rarecells, France) allowing the isolation and quantification of CTCs and CTMs, and immunocytochemistry (ICC) with anti-HER2. Results: The most common tumor status were T1b (15/20.8%) and N1 (14/19.4%) and diffuse tumors (Lauren's) was the most common subtype (37/51.4%); 55 patients had non-metastatic disease (76.4%) at moment of inclusion. CTCs were found in 61/72 patients (84.7%) with a median of 2.5 CTCs/mL (0-39.6 CTCs/mL). We found more CTC/mL in non-metastatic disease (2.8 CTCs/mL versus 0.9 CTCs/mL, p<0.001). CTMs were found in 28 patients (38.9%) and we also found more CTCs/mL CTM-positive cases (p<0.001). Among non-metastatic disease, 23/55 patients had CTM (41.8%) and in the metastatic scenario, 5/16 patients had CTM (31.3%). Besides finding no differences in the amount of CTCs between histological subtypes (intestinal versus diffuse), we observed more CTMs on diffuse GAC subtype compared to intestinal (69.6% x 30.4%). HER-2 status was evaluated in CTCs and primary tumor derived from 40 patients, with a level of concordance of 67.5%. Conclusions: CTCs were more prevalent in patients with initial disease, reinforcing their possible role in the growth of the primary tumor maybe in a self-seeding mechanism. Also, the good HER2-correlation found between primary tumors and CTCs suggest the use of the later as surrogates of the primary tumor for determining targeted therapies with anti-HER2 antibodies. Citation Format: Emne Ali Abdallah, Alexcia Camila Braun, Bianca Troncarelli Flores, Lais Lie Senda, Maria Dirlei Ferreira de Souza Begnami, Felipe José Coimbra, Emmanuel Dias-Neto, Diana Nunes, Wilson Luiz Costa Junior, Ludmilla T. Chinen. Circulating tumor cells and circulating tumor microemboli in the context of gastric adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1569.

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