The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

• Published in: The oncologist (Dayton, Ohio) Vol. 24; no. 9; pp. e854 - e863
• Main Authors: Abdallah, Emne A., Braun, Alexcia C., Flores, Bianca C.T.C.P., Senda, Laís, Urvanegia, Ana Cláudia, Calsavara, Vinicius, Fonseca de Jesus, Victor Hugo, Almeida, Maria Fernanda Arruda, Begnami, Maria Dirlei, Coimbra, Felipe J.F., da Costa, Wilson Luiz, Nunes, Diana Noronha, Dias‐Neto, Emmanuel, Chinen, Ludmilla T. Domingos
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2019
• Subjects: Circulating tumor cells; Circulating tumor microemboli; Gastric adenocarcinoma; Gastrointestinal Cancer; HER2; Plakoglobin; Circulating tumor microemboli; Gastric adenocarcinoma; Plakoglobin; Circulating tumor cells; HER2
• ISSN: 1083-7159; 1549-490X; 1549-490X
• DOI: 10.1634/theoncologist.2018-0741

Background Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data. Materials and Methods CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples). Results A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2‐negative primary tumors but HER2‐positive CTCs. A significant CTC count drop in follow‐up was seen for CTC‐HER2‐positive cases (4.45 to 1.0 CTCs per mL) compared with CTC‐HER2‐negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC‐plakoglobin‐positive cases (2.9 to 1.25 CTCs per mL). Conclusion CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC. Implications for Practice The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment. 摘要 背景。胃腺癌 (GAC) 是全球第三大致命恶性肿瘤，主要原因是疾病诊断较晚、化疗疗效较低以及对肿瘤生物学的整体认识不足。因此，我们需要用于预后及治疗反应预测工具。循环肿瘤细胞 (CTC) 和循环肿瘤微栓 (CTM) 的量化及其生物标志物的表达具有潜在的临床意义。我们的目的是评估 CTC 和 CTM 及其 HER2 和 plakoglobin在非转移性 GAC 患者中的表达，并将该发现与临床病理数据相关联。 材料和方法。使用上皮肿瘤细胞大小分离法进行 CTC 富集，并用免疫细胞化学和电子显微镜进行分析。制作了两个集合:一个在诊断时(新辅助化疗前 55 个样本)，一个在手术后和辅助性化疗前(33 个样本)。 结果。在基线观察到 CTC 检出率高 (90%)。我们评估了 45/55 个活检样本和 42/55 个 CTC 样本中的 HER2 的表达情况，其中有 36 名受试者表达重叠。除了在原发性肿瘤和成对 CTC 中观察到 HER2 表达的良好一致性 36 例(69.4%; κ = 0.272)，CTC 中 HER2 的分析显示与原发性肿瘤(11%)相比具有更高的阳性(43%)；3/5 名疾病进展的患者具有 HER2 阴性原发性肿瘤但为 HER2 阳性 CTC。与 CTC‐HER2 阴性病例(每毫升 2.6 至 1.0 个 CTC)相比，CTC‐HER2 阳性病例(每毫升 4.45 至 1.0 个 CTC)的跟进中 CTC 计数显着下降。在 CTC ‐ plakoglobin阳性病例(每毫升 2.9 至 1.25 个 CTC)中观察到相同情况。 结论。CTC 分析，包括其水平、plakoglobin和 HER2 表达，似乎是理解 GAC 生物学及预后的一种极具前途的工具。 实践意义:在新辅助治疗之前和之后对来自胃腺癌患者的血液中的循环肿瘤细胞水平进行分析有助于更好地理解疾病行为以及更可能对治疗产生反应的患者。 Gastric adenocarcinoma is the third deadliest malignant neoplasm worldwide. This article describes the results of an evaluation of HER2 expression in circulating tumor cells and plakoglobin in circulating tumor microemboli from nonmetastatic gastric adenocarcinoma patients.