The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, 500 03, Hradec Králové, Czech Republic.
2nd Department of Internal Medicine-Gastroenterology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, 500 03, Hradec Králové, Czech Republic.
Virchows Arch. 2020 Feb;476(2):231-241. doi: 10.1007/s00428-019-02627-4. Epub 2019 Aug 2.
Chronically inflamed mucosa in inflammatory bowel disease (IBD) is associated with an increased risk of cancer. Besides IBD-associated dysplasia, there are non-conventional mucosal changes that may act as potential precursors. The aim of the study was to retrospectively review samples from IBD patients focusing on detection of such lesions with evaluation of their immunohistochemical and molecular properties. Surgical specimens and/or endoscopical biopsy samples of IBD patients examined during a 10-year period were reviewed. Detected mucosal lesions were divided into three groups-group 1 (non-conventional or putative precursor lesions - PPLs) with serrated or villous hypermucinous morphology, group 2 (true serrated polyps fulfilling valid criteria), and group 3 (IBD-associated neoplasia). Lesions from all groups were analyzed with antibodies against MLH1, p53, and MGMT and by molecular testing of KRAS, NRAS, and BRAF mutation. Samples from 309 IBD patients were reviewed. A total of 88 mucosal lesions were found in 51 patients. Most common were lesions from group 1 with superficial serrated epithelial change seen in 41 samples (46.6%) and villous hypermucinous change in 6 (6.8%). Group 2 consisted of 15 true serrated polyps. Six conventional IBD-dysplasia cases and 11 carcinomas were seen in group 3. Six lesions from group 1 were associated with invasive carcinoma whereas two shared the same mutation in KRAS or BRAF. Lesions from group 1 were characterized by loss of MGMT expression in 44.6%, aberrant p53 expression, and by mutations in KRAS gene in 42.9% of cases. This study proves the existence of mucosal changes other than conventional IBD-dysplasia and extends the knowledge about their immunohistochemical and molecular properties and relation to carcinoma further supporting their potential role in IBD-related carcinogenesis.
慢性炎症性肠病（IBD）的黏膜与癌症风险增加有关。除了与 IBD 相关的异型增生外，还有非传统的黏膜变化可能作为潜在的前体。本研究的目的是回顾性分析 IBD 患者的样本，重点检测这些病变，并评估其免疫组织化学和分子特性。回顾了在 10 年期间检查的 IBD 患者的手术标本和/或内镜活检样本。将检测到的黏膜病变分为三组：第 1 组（非传统或假定的前体病变-PPLs）具有锯齿状或绒毛状高粘液性形态，第 2 组（符合有效标准的真正锯齿状息肉），第 3 组（IBD 相关肿瘤）。所有组别的病变均用针对 MLH1、p53 和 MGMT 的抗体进行分析，并通过 KRAS、NRAS 和 BRAF 突变的分子检测进行分析。对 309 例 IBD 患者的样本进行了回顾。在 51 名患者中发现了 88 处黏膜病变。最常见的是第 1 组病变，其中 41 例（46.6%）可见浅表锯齿状上皮改变，6 例（6.8%）可见绒毛状高粘液性改变。第 2 组包括 15 例真正的锯齿状息肉。第 3 组有 6 例传统的 IBD 异型增生病例和 11 例癌。第 1 组的 6 个病变与浸润性癌有关，而 2 个病变在 KRAS 或 BRAF 中具有相同的突变。第 1 组病变的特点是 44.6%存在 MGMT 表达缺失、异常的 p53 表达和 KRAS 基因的突变。本研究证明了除了传统的 IBD 异型增生之外，还存在其他黏膜变化，并进一步扩展了对其免疫组织化学和分子特性以及与癌的关系的认识，进一步支持了它们在 IBD 相关癌变中的潜在作用。
