Clinical, pathological genetics and intratumoral immune milieu of serrated adenocarcinoma of the colon

Histopathology. 2022 Sep;81(3):380-388. doi: 10.1111/his.14719. Epub 2022 Jul 20.


Background: Serrated adenocarcinoma (SAC), a recognised WHO variant of colonic adenocarcinoma, is the purported end-product of serrated neoplasia. However, the diagnosis of SAC is infrequently rendered, and little is known about its prognosis, immune microenvironment and molecular alterations.

Materials and methods: We assessed 903 consecutive colon carcinomas and recognised tumours with ≥ 5% (n = 77) serrated and ≥ 50% serrated patterns (n = 13). We assessed precursor polyps and synchronous polyps. We recorded demographic/clinical parameters, histological features and mismatch repair (MMR) status. We performed immunohistochemistry and quantification on tissue microarray for HLA class I/II proteins, B2MG, CD8, CD163, LAG3, FoxP3, PD-L1 and BRAF V600E.

Results: We identified ≥ 5% epithelial serration prevalence in 8.5% of cases and ≥ 50% epithelial serration prevalence in 1.4% of cases. Precursor lesions were present in 21.4% of cases; these were mostly tubular adenomas with two traditional serrated adenomas identified. SAC with ≥ 5% serrations exhibited lower numbers of CD8-positive lymphocytes (P = 0.002) and lower B2MG expression (P = 0.048), although neither value was significant at ≥ 50% serration threshold. There was no difference in HLA class I/II, or PD-L1 expression on tumour cells and no difference in PD-L1, LAG3, FoxP3 and CD163 expression on immune cells. There was no association with MMR status, or BRAFV600E relative to conventional adenocarcinoma. There was improved disease-specific survival on univariate (but not multivariate) analysis between carcinomas with serrated pattern and non-mucinous conventional colonic carcinomas at ≥ 5% epithelial serrations (P = 0.04).

Conclusion: SAC category shows a limited impact on survival, and this phenotype may harbour a unique immunological milieu.

Keywords: colon cancer; immune milieu; serrated adeoncarcinoma.

MeSH terms

  • Adenocarcinoma* / pathology
  • Adenoma* / pathology
  • B7-H1 Antigen / genetics
  • Biomarkers, Tumor / analysis
  • Carcinoma*
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / pathology
  • Colonic Polyps* / pathology
  • Colorectal Neoplasms* / pathology
  • Forkhead Transcription Factors
  • Humans
  • Proto-Oncogene Proteins B-raf / genetics
  • Tumor Microenvironment


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Forkhead Transcription Factors
  • Proto-Oncogene Proteins B-raf

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