Comprehensive characterization of micropapillary colorectal adenocarcinoma
Micropapillary colorectal adenocarcinoma is a morphologic subtype of colorectal cancer (CRC) with insufficiently characterized prognostic significance and biological features. We analyzed the histopathological, immunological, and prognostic features of micropapillary adenocarcinoma in two independent CRC cohorts (N = 1,876). We found that micropapillary adenocarcinomas accounted for 4.9% and 6.4% of CRCs in the two cohorts. A micropapillary growth pattern was associated with advanced stage and lymphovascular invasion (p < 0.001), but also with shorter overall survival independent of these factors and other prognostic parameters (Cohort 1: hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.08-2.87; Cohort 2: HR 1.47, 95% CI 1.08-2.00). Multiplex immunohistochemistry and machine learning-assisted image analysis showed that the micropapillary growth pattern was associated with decreased CD3<sup>+</sup> T-cell and CD14<sup>+</sup>HLA-DR<sup>+</sup> monocytic cell densities. Molecular features of micropapillary adenocarcinoma were studied using bioinformatic analyses in The Cancer Genome Atlas (TCGA) cohort (N = 629) and validated with optical genome mapping and immunohistochemistry. These analyses revealed that micropapillary adenocarcinomas frequently present with chromosome region 8q24 copy number gain, TP53 mutation, and overexpression of UPK2, MUC16, and epithelial-mesenchymal transition involved genes, such as L1CAM. These results indicate that micropapillary colorectal adenocarcinoma is an aggressive morphologic subtype of CRC characterized by shorter overall survival, decreased antitumorigenic immune response, and unique molecular features. Our findings support the classification of micropapillary adenocarcinoma as a distinct, high-risk subtype of CRC, which should be systematically evaluated in patient care. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Authors
- Maarit Ahtiainen (ORCID: https://orcid.org/0000-0002-3263-2307)
- Hanna Elomaa (ORCID: https://orcid.org/0000-0002-5378-7703)
- Ville K. Äijälä (ORCID: https://orcid.org/0009-0005-7664-8027)
- Juha Saarnio (ORCID: https://orcid.org/0000-0002-8443-3625)
- Olli Helminen (ORCID: https://orcid.org/0000-0001-9544-6475)
- Tero Rautio (ORCID: https://orcid.org/0000-0003-4441-9412)
- Jan Böhm (ORCID: https://orcid.org/0000-0001-9664-588X)
- Erkki‐Ville Wirta (ORCID: https://orcid.org/0000-0002-2255-6136)
- Toni T. Seppälä (ORCID: https://orcid.org/0000-0002-4940-3498)
- Katri Pylkäs (ORCID: https://orcid.org/0000-0002-2449-0521)
- Petri Pölönen (ORCID: https://orcid.org/0000-0001-6128-9985)
- Meeri Kastinen (ORCID: https://orcid.org/0009-0007-0954-5612)
- Sanna Meriläinen (ORCID: https://orcid.org/0000-0002-0789-9042)
- Markus J. Mäkinen (ORCID: https://orcid.org/0000-0002-9200-4118)
- Sara A. Väyrynen (ORCID: https://orcid.org/0000-0003-1768-0471)
- Päivi Sirniö (ORCID: https://orcid.org/0000-0002-3988-3782)
- Vesa‐Matti Pohjanen (ORCID: https://orcid.org/0000-0002-4129-4346)
- Jukka‐Pekka Mecklin (ORCID: https://orcid.org/0000-0003-4895-2249)
- Jouni Härkönen (ORCID: https://orcid.org/0000-0002-1201-4288)
- Henna Karjalainen (ORCID: https://orcid.org/0009-0008-4694-6703)
- Jukka M. J. Rintala (ORCID: https://orcid.org/0000-0003-1865-8444)
- Juha P. Väyrynen (ORCID: https://orcid.org/0000-0002-8683-2996)
- Anne Tuomisto (ORCID: https://orcid.org/0000-0002-9949-1887)
- Tuomo Mantere (ORCID: https://orcid.org/0000-0003-3284-4403)
- Vilja V. Tapiainen (ORCID: https://orcid.org/0009-0003-6306-6525)
- Onni Sirkiä (ORCID: https://orcid.org/0009-0003-8142-7144)
Institutions
- St. Jude Children's Research Hospital (US)
- University of Helsinki (FI)
- University of Eastern Finland (FI)
- Oulu University Hospital (FI)
- Helsinki University Hospital (FI)
- NordLab (FI)
- Tampere University Hospital (FI)
- Tampere University (FI)
- Central Finland Health Care District (FI)
- University of Jyväskylä (FI)
- University of Oulu (FI)
Publication Details
- Journal
- The Journal of Pathology
- Published
- 2025-02-07
- DOI
- https://doi.org/10.1002/path.6392
- Citations
- 8
- Primary Topic
- Colorectal Cancer Screening and Detection
- Type
- article
- Field-Weighted Citation Impact
- 8.36
Funders
- Suomen Lääketieteen Säätiö
- Sigrid Juséliuksen Säätiö
- Syöpäsäätiö