Dados do Resumo

Título

Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma

Introdução

Cancer is a disease where late diagnosis is often linked to poor prognosis, and early detection and effective management remain significant clinical challenges. Circulating tumor cells (CTCs) have emerged as a potential tool to improve the understanding and treatment of this disease. A recently discovered phenomenon in CTCs is cell fusion, which occurs when two or more cells merge, resulting in a single hybrid cell that exhibits characteristics of both progenitor cells. Although cell fusion is still poorly understood, it has been observed in in vitro and in vivo studies and may have significant implications for cancer progression and treatment.

Objetivo

The present study aims to analyze circulating tumor cells and hybrid cells in blood samples from patients with high-grade serous ovarian cancer. Specifically, we seek to correlate the presence of these cells and the expression of markers associated with cell fusion with the clinical outcomes of patients, such as recurrence-free survival (RFS).

Métodos

Blood samples (6 mL) were collected from 14 patients with high-grade serous ovarian cancer at A.C. Camargo Cancer Center in São Paulo, Brazil (protocol code 2623/18C). CTCs and hybrid cells were isolated and identified using the ISET (Isolation by Size of Epithelial Tumor Cells) technique. Markers such as MC1-R, EpCAM, and CD45 were used to assess their potential correlation with the cell fusion phenomenon. CEN8 expression was evaluated by CISH (Chromogenic In Situ Hybridization) analysis. Samples were collected at three time points: baseline, after one month of treatment with olaparib (first follow-up), and after three months (second follow-up). A total of 38 samples were analyzed.

Resultados

All 14 patients included in the study presented at least one CTC at baseline and first follow-up. The expression of MC1-R, EpCAM, and CD45 was observed in hybrid cells at least at one of the collection time points. Membrane staining with CD45 was detected in CTCs from another cohort evaluated by the CellSearch® system. The presence of circulating tumor microemboli (CTM) at the first follow-up was associated with a shorter recurrence-free survival (RFS) (5.2 vs. 12.2 months; p = 0.005). MC1-R expression in CTM at the first and second follow-ups was also associated with shorter RFS (p = 0.005). CEN8 expression in CTCs was related to shorter RFS as well (p = 0.035).

Conclusões

This study identified a high prevalence of CTCs and hybrid cells in ovarian cancer patients, suggesting that these cell subtypes may be useful in predicting prognosis and assessing treatment response. The expression of MC1-R and EpCAM in hybrid cells provides new perspectives as potential markers for this phenomenon in ovarian cancer.

Financiador do resumo

Donation from Faber-Castell (Brazil).
FAPESP, CNPq

Palavras Chave

circulating tumor cells; cell fusion; Ovarian cancer