Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello, 0424 Oslo, Norway.
Cancer Chemother Pharmacol. 2012 Feb;69(2):467-75. doi: 10.1007/s00280-011-1716-7. Epub 2011 Aug 6.
Equilibrative and concentrative nucleoside transporters (ENTs and CNTs) mediate the cellular uptake of anticancer nucleosides and sensitivity to such compounds. We studied the expression of ENTs and CNTs in ovarian carcinoma effusions.
ENT1, ENT2, ENT4 and CNT3 expression was analyzed in 66 ovarian carcinoma effusions (61 peritoneal, 5 pleural) from 64 ovarian carcinoma patients by flow cytometry. The majority of patients received platinum-based chemotherapy. Results were analyzed for association with clinicopathologic parameters and survival.
With the exception of one ENT2-negative effusion, ENT1, ENT2, ENT4 and CNT3 protein was detected on carcinoma cells in all effusions, with expression observed in 1-95% of tumor cells. Nucleoside transporter expression was comparable between peritoneal and pleural effusions and was unrelated to age, tumor grade, International Federation of Gynecology and Obstetrics (FIGO) stage, residual tumor volume after surgery, previous exposure to chemotherapy and response to chemotherapy at diagnosis (P > 0.05). No correlation was found between ENT or CNT expression and overall survival or progression-free survival, although higher ENT2 expression was associated with a trend for longer overall (45 vs. 23 months; P = 0.055) and progression-free (17 vs. 5 months; P = 0.087) survival.
Nucleoside transporters are frequently expressed in ovarian carcinoma effusions, but their expression generally appears to be unrelated to chemoresponse in this cancer in a cohort of patients treated by platinum-based chemotherapy. The role of ENT2 as a prognostic marker in this disease, as well as the role of these molecules in determining chemoresponse in patients treated by nucleoside analogs, merits further research.
平衡核苷转运体（ENTs）和协同核苷转运体（CNTs）介导抗肿瘤核苷的细胞摄取和对这些化合物的敏感性。我们研究了卵巢癌性胸腹水核苷转运体的表达。
采用流式细胞术分析 64 例卵巢癌患者的 66 份卵巢癌性胸腹水（61 份腹腔，5 份胸腔）中 ENT1、ENT2、ENT4 和 CNT3 的表达。大多数患者接受了铂类化疗。分析结果与临床病理参数和生存的关系。
除了 1 份 ENT2 阴性胸腹水外，所有胸水中的癌细胞均检测到 ENT1、ENT2、ENT4 和 CNT3 蛋白，肿瘤细胞表达率为 1%-95%。腹腔和胸腔积液中核苷转运体的表达无差异，与年龄、肿瘤分级、国际妇产科联盟（FIGO）分期、手术残留肿瘤体积、既往化疗暴露和诊断时化疗反应无关（P>0.05）。未发现 ENT 或 CNT 表达与总生存或无进展生存相关，尽管 ENT2 表达较高与总生存（45 个月比 23 个月；P=0.055）和无进展生存（17 个月比 5 个月；P=0.087）趋势相关。
核苷转运体在卵巢癌性胸水中频繁表达，但在接受铂类化疗的患者队列中，其表达通常与化疗反应无关。ENT2 作为该疾病的预后标志物的作用，以及这些分子在决定接受核苷类似物治疗的患者化疗反应中的作用，值得进一步研究。
