Abstract
BackgroundPatients with inflammatory bowel disease (IBD) – ulcerative colitis (UC) and Crohn’s disease (CD) have an elevated risk of developing colorectal carcinoma (CRC). Major risk factor in IBD patients is the continuous chronic inflammation leading to development of dysplasia and carcinoma. Nevertheless, other types of non-conventional but suspicious mucosal changes serrated change/dysplasia, NOS and villous hypermucinous change, have also been reported in IBD patients. Preneoplastic potential of these lesions is still not well elucidated. AimsThe aim of this study was identification of IBD-associated CRCs focusing on finding related precursor lesions in the surgical specimen or in archival biopsy samples followed by a detailed morphological, immunohistochemical and molecular evaluation. For the purpose of the study the mucosal lesions were divided into conventional IBD-associated dysplasia and non-conventional lesions that were merged under a provisory term of putative preneoplastic lesions (PPL). MethodsA total of 309 consecutive IBD colectomy specimens diagnosed during a 10-year period were reviewed. Detailed morphological evaluation, immunohistochemical analysis of mismatch repair (MMR) proteins, p53 and O6-methylguanine DNA methyltransferase (MGMT) expression and molecular analysis for KRAS, NRAS and BRAF gene mutation were performed in the retrieved CRC cases as well as in the detected dysplasia and PPLs of these patients. ResultsWe identified 11 cases of morphologically heterogenous IBD-associated CRCs, occurring in 5 males and 6 females, aged 26–79 years (mean 44 years). A total of 22 mucosal lesions were revealed in 8 CRC patients comprising conventional IBD-associated dysplasia (4 lesions), PPLs as serrated change/dysplasia NOS (11 lesions), villous hypermucinous change (5 lesions), and two true serrated lesions (one sessile serrated adenoma and one traditional serrated adenoma). More than one type of lesion was found in 6 patients. Seven CRC cases harbored mutation of KRAS/NRAS and one case of BRAF. Two patients with KRAS-mutated CRC showed the same mutation in PPL in the same specimen (one serrated change NOS and one TSA with high-grade dysplasia). Similarly, one BRAF-mutated carcinoma case presented the same mutation in serrated change/dysplasia, NOS in the same specimen. Of the CRCs, two showed deficient MMR system profile, six presented with loss of MGMT expression, and six showed aberrant p53 expression. PPLs showed deficient MGMT expression (14 cases) and aberrant p53 (10 cases) as well. ConclusionIBD-associated CRCs are very heterogeneous entities. Besides conventional IBD-related dysplasia, other types of mucosal lesions may be associated with long lasting IBD and CRC e.g. villous hypermucinous change and serrated change/dysplasia, NOS. Since these lesions share certain genetic or immunohistochemical changes with the related CRC, a suspicion is raised that these lesions may also have preneoplastic potential. Awareness of these changes is necessary to prevent their missing and under-reporting, and further studies of these lesions should be carried out.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.