Institute for Pathology, Friedrich-Alexander University Erlangen-Nürnberg, Klinikum Bayreuth, D-95445 Bayreuth, Germany.
Medical Department 1, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Discov Med. 2024 Jul;36(186):1363-1369. doi: 10.24976/Discov.Med.202436186.126.
Ulcerative colitis is a well-known inflammatory bowel disease. Patients have an increased risk of developing colitis associated carcinoma (CAC). It is important for patient management to be able to distinguish between ulcerative colitis associated carcinoma and sporadic carcinoma (sCRC). However, this distinction is frequently very challenging. It is not readily possible to differentiate this histologically. However, the diagnosis is crucial for the patient's further treatment and follow-up. An attempt was therefore made to develop a diagnostic regime that would enable a reliable distinction between sCRC and CAC.
We screened 96 patients analyzing more than 850,000 methylation hotspots, to detect distinct epigenetic patterns between both types of carcinomas. Patients with sporadic carcinoma and colitis-associated carcinoma as well as patients with normal colon and patients with confirmed ulcerative colitis without neoplasia were used for the analysis. By extensively filtering the results, methylation sites relevant to distinguish between CAC and sCRC were identified.
After the results were filtered, three methylation sites relevant to distinguish between CAC and sCRC were identified. For this purpose, methylation limit values were defined, which favor the samples as CAC or sCRC up to a certain methylation value of the methylation sites. The combination of three methylation sites allows a correct assignment to CAC or sCRC in 94.5% of the cases.
The results show that these three methylation sites are promising markers in the diagnosis of CAC vs sCRC. Nevertheless, the diagnosis should always be made in conjunction with histomorphological analyses.
溃疡性结肠炎是一种众所周知的炎症性肠病。患者发生结肠炎相关癌（CAC）的风险增加。能够区分溃疡性结肠炎相关癌和散发性癌（sCRC）对于患者管理非常重要。然而，这种区分通常极具挑战性。在组织学上很难区分这两种癌症。但是，这种诊断对于患者的进一步治疗和随访至关重要。因此，我们试图开发一种诊断方案，以实现 sCRC 和 CAC 之间的可靠区分。
我们筛选了 96 名患者，分析了超过 85 万个甲基化热点，以检测两种类型的癌之间是否存在独特的表观遗传模式。分析使用了散发性癌和结肠炎相关癌患者、正常结肠患者和经证实患有溃疡性结肠炎但无肿瘤的患者。通过广泛过滤结果，确定了区分 CAC 和 sCRC 的甲基化位点。
在对结果进行过滤后，确定了三个与区分 CAC 和 sCRC 相关的甲基化位点。为此，定义了甲基化限值，这些限值有利于将样本归类为 CAC 或 sCRC，直到甲基化位点的甲基化值达到一定程度。三个甲基化位点的组合可使 94.5%的病例正确分配到 CAC 或 sCRC。
结果表明，这三个甲基化位点是诊断 CAC 与 sCRC 的有前途的标志物。然而，诊断应始终结合组织形态学分析进行。
