First Department of Surgery, Jagiellonian University Medical College, 40 Kopernika Street, Kraków, 31-501, Poland.
Department of Clinical Immunology, Jagiellonian University Medical College, 265 Wielicka Street, 30-663, Kraków, Poland.
Gastric Cancer. 2019 Mar;22(2):264-272. doi: 10.1007/s10120-018-0858-2. Epub 2018 Jul 28.
The phenotypic heterogeneity of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in bone marrow is an important constraint for clinical decision making. Here, we investigated the implications of two different subpopulations of these cells in gastric cancer (GC).
GC patients (n = 228) who underwent elective gastric resections were prospectively examined for CTC/DTC. The cells obtained from peripheral blood and bone marrow aspirates were sorted by flow cytometry and CD45 cells expressing cytokeratins (8, 18, and 19) and CD44 were identified by immunofluorescent double staining.
Ninety-three (41%) patients had cytokeratin-positive tumor cells in either blood or bone marrow, while cells expressing CD44 were found in 22 (10%) cases. CKCD44 cells were significantly more common among patients with distant metastases (50 vs 19%, P = 0.001), while no such correlations were demonstrated for CKCD44 cells. Detection of CKCD44 cells, but not CKCD44, was associated with significantly shortened survival. Moreover, the Cox proportional hazards model identified CKCD44 cells as a negative prognostic factor with an odds ratio of 2.38 (95% CI 1.28-4.41, P = 0.006).
CD44 phenotype of cytokeratin-positive cells in blood and bone marrow is an independent prognostic factor in patients with gastric cancer.
外周血循环肿瘤细胞(CTC)和骨髓播散肿瘤细胞(DTC)的表型异质性是临床决策的重要限制因素。在这里,我们研究了这些细胞的两种不同亚群在胃癌(GC)中的意义。
前瞻性检查了 228 例接受择期胃切除术的 GC 患者的 CTC/DTC。通过流式细胞术对来自外周血和骨髓抽吸物的细胞进行分选,并通过免疫荧光双重染色鉴定表达细胞角蛋白(8、18 和 19)和 CD44 的 CD45 细胞。
93 例(41%)患者的血液或骨髓中存在细胞角蛋白阳性肿瘤细胞,而 22 例(10%)患者中存在表达 CD44 的细胞。CKCD44 细胞在远处转移患者中更为常见(50%比 19%,P=0.001),而 CKCD44 细胞则没有相关性。检测 CKCD44 细胞而非 CKCD44 细胞与生存时间明显缩短相关。此外,Cox 比例风险模型将 CKCD44 细胞鉴定为具有负预后的因素,优势比为 2.38(95%CI 1.28-4.41,P=0.006)。
血液和骨髓中细胞角蛋白阳性细胞的 CD44 表型是胃癌患者的独立预后因素。