Keane Margaret G, Huggett Matthew T, Chapman Michael H, Johnson Gavin J, Webster George J, Thorburn Douglas, Mackay James, Pereira Stephen P
Institute for Liver and Digestive Health, University College London, Royal Free Campus, Pond St, London NW3 2PF, UK.
Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BG, UK.
Br J Cancer. 2017 Jan;116(3):349-355. doi: 10.1038/bjc.2016.447. Epub 2017 Jan 12.
Biliary brush cytology is the standard method of evaluating biliary strictures, but is insensitive at detecting malignancy. In pancreaticobiliary cancer minichromosome maintenance replication proteins (MCM 2-7) are dysregulated in the biliary epithelium and MCM5 levels are elevated in bile samples. This study aimed to validate an immunocolorimetric ELISA assay for MCM5 as a pancreaticobiliary cancer biomarker in biliary brush samples.
Biliary brush specimens were collected prospectively at ERCP from patients with a biliary stricture. Collected samples were frozen at -80 °C. The supernatant was washed and lysed cells incubated with HRP-labelled anti-MCM5 mouse monoclonal antibody. Test positivity was determined by optical density absorbance. Patients underwent biliary brush cytology or additional investigations as per clinical routine.
Ninety-seven patients were included in the study; 50 had malignant strictures. Median age was 65 years (range 21-94) and 51 were male. Compared with final diagnosis the MCM5 assay had a sensitivity for malignancy of 65.4% compared with 25.0% for cytology. In the 72 patients with paired MCM5 assay and biliary brush cytology, MCM5 demonstrated an improved sensitivity (55.6% vs 25.0%; P=0.0002) for the detection of malignancy.
Minichromosome maintenance replication protein5 is a more sensitive indicator of pancreaticobiliary malignancy than standard biliary brush cytology.
胆管刷检细胞学是评估胆管狭窄的标准方法，但在检测恶性肿瘤方面不敏感。在胰胆管癌中，微小染色体维持复制蛋白（MCM 2 - 7）在胆管上皮中表达失调，且胆汁样本中MCM5水平升高。本研究旨在验证一种用于检测胆管刷检样本中MCM5的免疫比色ELISA检测法，将其作为胰胆管癌的生物标志物。
前瞻性收集接受内镜逆行胰胆管造影（ERCP）检查的胆管狭窄患者的胆管刷检标本。收集的样本在-80°C下冷冻。洗涤上清液，将裂解的细胞与辣根过氧化物酶（HRP）标记的抗MCM5小鼠单克隆抗体孵育。通过光密度吸光度确定检测阳性。患者按照临床常规接受胆管刷检细胞学检查或其他进一步检查。
97例患者纳入本研究；50例有恶性狭窄。中位年龄为65岁（范围21 - 94岁），51例为男性。与最终诊断相比，MCM5检测法对恶性肿瘤的敏感性为65.4%，而细胞学检查为25.0%。在72例同时进行MCM5检测和胆管刷检细胞学检查的患者中，MCM5在检测恶性肿瘤方面显示出更高的敏感性（55.6%对25.0%；P = 0.0002）。
微小染色体维持复制蛋白5是比标准胆管刷检细胞学更敏感的胰胆管恶性肿瘤指标。
