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Original research
Quantitative p53 immunostaining aids in the detection of prevalent dysplasia
  1. Azfar Neyaz1,
  2. Steffen Rickelt2,
  3. Omer H Yilmaz1,
  4. Paige H Parrack3,
  5. Chenyue Lu4,
  6. Osman Yilmaz5,
  7. Elizabeth Y Wu6,
  8. Won-Tak Choi7,
  9. Manish Gala8,
  10. David T Ting4,
  11. Robert D Odze3,
  12. Deepa T Patil3,
  13. Vikram Deshpande5
  1. 1Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  3. 3Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  4. 4Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA
  5. 5Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  6. 6Pathology, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
  7. 7Pathology, University of California, San Francisco, California, USA
  8. 8Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Vikram Deshpande, Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; vikramdirdeshpande{at}gmail.com

Abstract

Aims The lack of accepted scoring criteria has precluded the use of p53 in routine practice. We evaluate the utility of automated quantitative p53 analysis in risk stratifying Barrett’s oesophagus (BE) patients using non-dysplastic BE (NDBE) biopsies in a multicentric cohort of BE progressor (P) and non-progressor (NP) patients.

Methods NDBE biopsies prior to the diagnosis of advanced neoplasia from 75 BE-P, and index and last surveillance biopsies from 148 BE-NP were stained for p53, and scored digitally as 1+, 2+ and 3+. A secondary cohort of 30 BE-P was evaluated.

Results Compared with BE-NP, BE-P was predominantly men (p=0.001), ≥55 years of age (p=0.008), with longer BE segments (71% vs 33%; p<0.001). The mean number of 3+p53 positive cells and 3+ positive glands were significantly more in BE-P versus BE-NP NDBE biopsies (175 vs 9.7, p<0.001; 9.8 vs 0.1; p<0.001, respectively). At a cut-off of ≥10 p53 (3+) positive cells, the sensitivity and specificity of the assay to identify BE-P were 39% and 93%. On multivariate analysis, scoring p53 in NDBE biopsies, age, gender and length of BE were significantly associated with neoplastic progression. 54% of patients classified as prevalent dysplasia showed an abnormal p53 immunohistochemical stain. These findings were validated in the secondary cohort.

Conclusions Automated p53 analysis in NDBE biopsies serves as a promising tool for assessing BE neoplastic progression and risk stratification. Our study highlights the practical applicability of p53 assay to routine surveillance practice and its ability to detect prevalent dysplasia.

  • Barrett Esophagus
  • Gastrointestinal Neoplasms
  • IMMUNOHISTOCHEMISTRY

Data availability statement

Data are available on reasonable request. Data, analytical methods and study materials will be made available to other researchers on request.

http://dx.doi.org/10.1136/jcp-2022-208721

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    Data availability statement

    Data are available on reasonable request. Data, analytical methods and study materials will be made available to other researchers on request.

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    Footnotes

    • DTP and VD contributed equally.

    • Contributors AN: conceptualisation, sample collection, data curation, data analysis, methodology, original draft writing, review and editing, SR: conceptualisation, data curation, methodology, OY: resources, review and editing, PP: data curation, CL: data analysis, methodology, automated image analysis software support, OY: sample and data collection, EYW: sample and data collection, W-TC: sample and data collection, MG: conceptualisation, data curation, original draft writing, DTT: conceptualisation, data curation, data analysis, methodology, resources, original draft writing, RO: supervision, conceptualisation, data curation, data analysis, methodology, original draft writing, DP: supervision, conceptualisation, data curation, data analysis, original draft writing, review and editing, VD: supervision, conceptualisation, data curation, data analysis, original draft writing, review and editing. All authors: final approval of the manuscript. DP and VD are joint last authors, Guarantor of the manuscript: VD.

    • 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 None declared.

    • 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.