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Original research
LGR5 as a diagnostic marker for dysplasia in serrated polyps
  1. Osman Yilmaz1,
  2. Kshtij Arora2,
  3. Soo Hyun Lee3,
  4. Sahar Hosseini4,
  5. Feidi Chen4,
  6. Nandan Padmanabha5,
  7. George Eng4,
  8. Kanchan Kantekure4,
  9. Omer Yilmaz6,
  10. Vikram Deshpande4
  1. 1Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  2. 2Massachusetts General Hospital, Wuincy, Massachusetts, USA
  3. 3Boston Medical Center, Boston, Massachusetts, USA
  4. 4Harvard Medical School, Boston, Massachusetts, USA
  5. 5Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  6. 6Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Vikram Deshpande; vikramdirdeshpande{at}gmail.com

Abstract

Aims WNT signalling pathway dysregulation is often a critical early component in colorectal neoplasia, particularly the chromosomal instability pathway. Using two WNT reporters, LGR5 and AXIN2, we sought to assess whether these polyps demonstrate predictable expression patterns and if these patterns show diagnostic value.

Methods We evaluated 23 adenomas (TA), 23 sessile serrated lesions (SSLs), 14 SSL with dysplasia and 38 traditional serrated adenomas (TSA). Chromogenic in situ hybridisation stains (ISH) for LGR5 and AXIN2 were performed. Reactivity was defined as strong, intermediate or weak. Upper third crypt reactivity was defined as full-thickness staining. Accentuation within ectopic crypts (ECF) was recorded.

Results TAs (91%) showed strong reactivity and full-thickness staining with LGR5. TSAs showed full-thickness and weak to intermediate LGR5 reactivity (79%) and ECF with LGR5 accentuation was exclusively seen in TSA. SSL showed weak LGR5 reactivity confined to the basal crypt region (100%). SSL with dysplasia also showed weak or intermediate (100%) LGR5 reactivity, but the reactivity pattern was full thickness (88%). AXIN2 expression parallels LGR5 expression (Pearson coefficient=0.63) regarding signal intensity for the examined polyp groups.

Conclusions Qualitative and quantitative differences in AXIN2 and LGR5 expression assist in the diagnosis of SSL with dysplasia.

  • COLON
  • Colorectal Neoplasms
  • In Situ Hybridisation

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/jcp-2024-209856

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors Osman Yilmaz and VD contributed to conception, design, data collection, analysis, writing and final approval of the manuscript. KA, FC, NP, Omer Yilmaz, KK and SH contributed to data collection. GE and SHL contributed to analysis. VD and Osman Yilmaz are guarantors of the article and responsible for its overall content.

    • Funding VD previously received research support from Affymetrix, California, USA and currently receive research support from Advanced Cell Diagnostics/Bio-Techne.

    • Competing interests This work was funded by Affymetrix (VD) and Advanced Cell Diagnostics/ Bio-Techne (VD) and internal funds. One of the co-authors (VD) is an editor of this journal.

    • 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.