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

在疾病的早期阶段诊断胰腺癌和胆管癌仍然很困难，而且还没有既定的测试来筛查患有这些癌症的高危患者，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)。血液测试和扫描通常不够准确，无法确认癌症的存在，因此通常从狭窄的胆管内壁用刷子(刷子细胞学)获取细胞，以便在显微镜下寻找癌症。然而，刷检细胞学只能在20%-50%的病例中发现癌症，这意味着患者经常不得不接受额外的侵入性程序，导致潜在的并发症和诊断延误。显然需要更好的诊断测试。本研究的目的是测试被称为微小染色体维持蛋白(MCM2-7)的新的潜在标记物，该标记物可能有助于早期发现癌前病变和累及胆管的癌症，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，在各种早期和晚期癌症中，这些蛋白的水平都会升高，可以作为宫颈癌、食道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，结果表明，在胆汁中检测到MCM 5蛋白时，在检测胰腺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。这项测试的准确性部分取决于有多少细胞可供测试。刷状细胞学包含的细胞比胆汁多得多，我们现在有了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，几乎100%的癌症可以被检测到。因此，我们计划通过研究这一标记物来证实这些结果，这是一项大型多中心研究的一部分，研究对象包括胰腺癌和胆道癌的高危患者。

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.