Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance proteins in cytological specimens

胰腺癌和胆管癌在疾病早期的诊断仍然很困难，并且没有既定的测试来筛选患有这些癌症的高风险患者，例如慢性胰腺炎（风险增加20倍）和原发性硬化性胆管炎（风险增加160倍）。血液检查和扫描通常不足以准确地确认癌症的存在，因此细胞通常是从狭窄的胆管内壁用刷子（刷细胞学）在显微镜下寻找癌症。然而，刷检细胞学仅在20-50%的病例中检测到癌症，这意味着患者通常必须接受额外的侵入性手术，导致潜在的并发症和诊断延迟。显然需要更好的诊断测试。 这项研究的目的是测试一种新的潜在标记物，即微小染色体维持蛋白（mcm 2-7），它可以提高癌前病变和胆管癌的早期检测，从而提高胰腺癌和胆管癌患者的寿命和生活质量。这些蛋白质是DNA复制所必需的，而DNA复制是所有癌细胞繁殖和生长所必需的。我们已经证明，与良性组织相比，这些蛋白质的水平在各种早期和晚期癌症中增加，并且可以用作宫颈癌，食管癌和膀胱癌的准确诊断测试。 我们最近完成了一项对102名患者的研究，该研究表明，在胆汁中检测到的Mcm 5蛋白在检测胰腺癌和胆道癌方面比刷检细胞学好三倍以上，高达80%的癌症被正确诊断。这种测试的准确性部分取决于有多少细胞可供测试。刷状细胞学包含比胆汁更多的细胞，我们现在有令人兴奋的早期结果表明，当在刷状细胞学标本中检测到Mcm 5时，可以检测到接近100%的癌症。因此，我们计划通过研究这种标记物来证实这些结果，作为一项大型多中心研究的一部分，包括胰腺癌和胆管癌高危患者。

The diagnosis of pancreatic and bile duct cancer at an early stage of disease remains difficult and there are no established tests to screen patients at high-risk of developing these cancers such as those with chronic pancreatitis (20x increased risk) and primary sclerosing cholangitis (160x increased risk). Blood tests and scans are not usually accurate enough to confirm the presence of cancer so cells are usually obtained from the lining of a narrowed bile duct with a brush (brush cytology) to look for cancer under the microscope. Brush cytology however only detects cancer in 20-50% of cases which means that patients often have to undergo additional invasive procedures, leading to potential complications and delays in diagnosis. Better diagnostic tests are clearly needed. The aim of this study is to test new potential markers called minichromosome maintenance proteins (mcm 2-7) which may improve the early detection of precancerous changes and cancers involving the bile duct, and thus enhance the longevity and quality of life of patients living with pancreatic and bile duct cancer. These proteins are necessary for DNA replication which is essential for all cancer cells to multiply and grow. We have shown that the levels of these proteins are increased in a wide variety of early and advanced cancers in comparison to benign tissues, and can be used as accurate diagnostic tests for cervical, oesophageal and bladder cancer. We have recently completed a study of 102 patients which showed that Mcm 5 protein when detected in bile is more than three times better than brush cytology at detecting pancreatic and biliary tract cancer, with up to 80% of cancers correctly diagnosed. The accuracy if this test depends in part on how many cells there are available to test. Brush cytology contains many more cells than bile and we now have exciting early results indicating that when Mcm 5 is detected in brush cytology specimens, close to 100% of cancers may be detected. We therefore plan to confirm these results by studying this marker as part of a large multicentre study, including patients at high risk of developing pancreatic and bile duct cancer.