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Original research
Clinical, pathological, genetics and intratumoural immune milieu of micropapillary carcinoma of the colon
  1. Vikram Deshpande1,
  2. Soo Hyun Lee2,
  3. Andrew Crabbe3,
  4. Amaya Pankaj4,
  5. Azfar Neyaz5,
  6. Yuho Ono1,
  7. Steffen Rickelt6,
  8. Swati Sonal7,
  9. Cristina R Ferrone8,
  10. David T Ting4,9,
  11. Deepa Patil10,
  12. Omer Yilmaz3,6,11,
  13. David Berger8,12,
  14. Osman Yilmaz1,11
  1. 1 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  2. 2 Department of Pathology, Boston Medical Center, Boston, Massachusetts, USA
  3. 3 Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
  4. 4 Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  5. 5 Department of Pathology, UPMC, Pittsburgh, Pennsylvania, USA
  6. 6 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  7. 7 Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
  8. 8 Depatment of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
  9. 9 Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA
  10. 10 Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  11. 11 Harvard Medical School, Boston, Massachusetts, USA
  12. 12 Massachusetts Gen Hosp, Boston, Massachusetts, USA
  1. Correspondence to Dr Osman Yilmaz, Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; osmanhy{at}gmail.com

Abstract

Aim Micropapillary carcinoma (MPC) is a recognised WHO variant of colonic carcinoma (CC), although little is known about its prognosis, immune microenvironment and molecular alterations. We investigated its clinical, pathological and immunological characteristics.

Methods We assessed 903 consecutive CCs and used the WHO definition to identify MPC. We recorded serrated and mucinous differentiation and mismatch repair (MMR) status. We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, PD-L1and BRAF V600E.

Results We classified 8.6% (N=78) of CC as MPC. Relative to non-MPC, MPC was more often high grade (p=0.03) and showed serrated morphology (p<0.01); however, we found no association with extramural venous invasion (p=0.41) and American Joint Committee on Cancer stage (p=0.95). MPCs showed lower numbers of CD8 positive lymphocytes (p<0.01), lower tumour cell B2MG expression (p=0.04) and lower tumour cell PD-L1 expression (p<0.01). There was no difference in HLA class I/II, LAG3, FOXP3, CD163 and PD-L1 positive histiocytes. There was no association with MMR status or BRAF V600E relative to non-MPC. MPC was not associated with decreased disease-specific survival (p=0.36).

Conclusion MPCs are associated with high-grade differentiation and a less active immune microenvironment than non-MPC. MPC is not associated with inferior disease-specific survival.

  • COLON
  • IMMUNOHISTOCHEMISTRY
  • Colorectal Neoplasms

Data availability statement

Data are available on reasonable request. The data that support the findings of this study are not openly available to maintain patient confidentiality, but deidentified data are available from the corresponding author on reasonable request.

https://doi.org/10.1136/jcp-2023-208895

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    Data availability statement

    Data are available on reasonable request. The data that support the findings of this study are not openly available to maintain patient confidentiality, but deidentified data are available from the corresponding author on reasonable request.

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    Footnotes

    • Handling editor Runjan Chetty.

    • X @YuhoMD

    • Contributors OY and VD performed study concept and design; AC, AP, AN, YO and SR performed development of methodology; SS, CRF, DTT, DP, OY and DLB provided acquisition of data and reveiw paper; SHL, OY and VD analyse and interpretate data; SHL, OY and VD performed writing the paper. All authors reviewed and approved the final paper. OY is the author acting as 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 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.

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