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Molecular profiling of visible polypoid and invisible conventional intestinal-type low-grade dysplasia in patients with idiopathic inflammatory bowel disease
  1. Alexander Christakis1,
  2. Jonathan Nowak1,
  3. Matthew J Hamilton2,
  4. John R Goldblum3,
  5. Paige Parrack1,
  6. Neal I Lindeman1,
  7. Robert Odze1,
  8. Deepa T Patil1
  1. 1Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
  2. 2Department of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA
  3. 3Department of Pathology, Cleveland Clinic, Cleveland, OH, USA
  1. Correspondence to Dr Deepa T Patil, Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA; Deepa.patil{at}uhhospitals.org

  • Present affiliation The present affiliation of Neal I Lindeman is: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA

  • Present affiliation The present affiliation of Robert Odze is: Department of Pathology and Lab Medicine, Tufts University School of Medicine, Boston, MA, USA

  • Present affiliation The present affiliation of Deepa T Patil is: Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

Abstract

Aims Little is known about the molecular features of visible polyps with low-grade intestinal-type dysplasia in patients with inflammatory bowel disease (IBD). To better understand their origins and biological potential, we sought to genomically profile these lesions and compare them with invisible low-grade dysplasia and sporadic adenomas from non-IBD patients.

Methods 22 polyps within areas of colitis, 13 polyps outside areas of colitis, 10 foci of invisible dysplasia from patients with IBD and 6 sporadic tubular adenomas from non-IBD patients were analysed using the OncoPanel assay.

Results Polyps arising in areas of colitis showed a greater spectrum of mutations, including APC, KRAS, FBXW7, TP53, ARID1A and TCF7L2. Polyps outside colitis and non-IBD sporadic adenomas showed a limited mutational profile, with APC and CTNNB1 mutations. Invisible dysplasia was characterised by TP53, CTNNB1 and KRAS alterations. Compared with dysplastic polyps, none of the invisible dysplastic foci showed APC alterations (73%—within colitis; p=0.0001, 92%—outside colitis; p<0.0001, 83%—sporadic adenomas; p=0.001). TP53 mutations were significantly higher in invisible dysplasia (50%) compared with polyps within colitis (9%; p=0.02) and outside colitis (8%; p=0.03).

Conclusions Molecular alterations in visible low-grade dysplastic polyps with conventional intestinal-type dysplasia from patients with IBD and sporadic adenomas from non-IBD patients overlap significantly. APC alterations appear to play a major role in the development of visible low-grade dysplastic lesions in patients with IBD, regardless of background colitis. As with IBD-associated colorectal cancers, TP53 mutations are an early event in the development of invisible, low-grade conventional intestinal-type dysplasia in patients with IBD.

  • COLITIS
  • COLON
  • Gastrointestinal Neoplasms

Data availability statement

Please email all requests for academic use of raw and processed data to the corresponding author. Restrictions apply to the availability of the in-house and external data, which were used with institutional permission for the current study, and are thus not publicly available. All requests will be promptly evaluated based on institutional and departmental policies to determine whether the data requested is subject to intellectual property or patient privacy obligations. Data can only be shared for non-commercial academic purposes and will require a data user agreement.

https://doi.org/10.1136/jcp-2024-209601

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    Data availability statement

    Please email all requests for academic use of raw and processed data to the corresponding author. Restrictions apply to the availability of the in-house and external data, which were used with institutional permission for the current study, and are thus not publicly available. All requests will be promptly evaluated based on institutional and departmental policies to determine whether the data requested is subject to intellectual property or patient privacy obligations. Data can only be shared for non-commercial academic purposes and will require a data user agreement.

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    Footnotes

    • Handling editor Vikram Deshpande.

    • Contributors AC, RO and DTP designed the study. AC, JN, MJH, PP, JRG and DTP collected the data. AC, JN, NIL, RO and DTP analysed the data. AC, JN and DTP drafted the manuscript. JN, MJH, PP, JRG, NIL, RO and DTP revised the manuscript. DTP is responsible for the overall content as the guarantor.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests One of the coauthors is an associate editor (DTP). None of the authors have any competing financial interests in relation to the work described.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.