Significance of mucin-suspended tumor bud-like structures in colorectal cancer
Tumor budding (TB) is an independent predictor of adverse prognosis in colorectal cancer (CRC), defined as clusters of fewer than 5 tumor cells at the invasive margin of cancer. According to the international consensus criteria (ITBCC), TB should be evaluated from the non-mucinous regions. However, some tumors also contain tumor bud-like structures within extracellular mucin pools, and the prognostic impact of these structures remains unclear. To assess this, we defined a modified tumor budding variable (TB-Muc), representing the highest number of tumor buds/bud-like structures observed in a hotspot (0.785 mm<sup>2</sup>) at the invasive margin, including extracellular mucin regions. We analyzed the prognostic significance of TB (ITBCC criteria) and TB-Muc in two CRC cohorts (N = 1876). TB-ITBCC was associated with advanced stage and lymphovascular invasion (p < 0.001) but also with shorter cancer-specific survival independent of other prognostic factors (Cohort 1: HR for high vs. low 1.99, 95 % CI 1.32-3.01, p<sub>trend</sub> = 0.0007; Cohort 2: HR 1.35, 95 % CI 0.98-1.85, p<sub>trend</sub> = 0.037). TB-Muc had a comparable independent association with shorter cancer-specific survival (Cohort 1: HR for high vs. low 1.77, 95 % CI 1.18-2.65, p<sub>trend</sub> = 0.006; Cohort 2: HR 1.39, 95 % CI 1.02-1.89, p<sub>trend</sub> = 0.019). Our results indicate that tumor bud-like structures in mucin do not provide additional prognostic value and should not be included in TB evaluation.
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)
- 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)
- Päivi Sirniö (ORCID: https://orcid.org/0000-0002-3988-3782)
- Jukka‐Pekka Mecklin (ORCID: https://orcid.org/0000-0003-4895-2249)
- 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)
- Vilja V. Tapiainen (ORCID: https://orcid.org/0009-0003-6306-6525)
Institutions
- Oulu University Hospital (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
- Human Pathology
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1016/j.humpath.2025.105772
- Citations
- 2
- Primary Topic
- Colorectal Cancer Treatments and Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- Suomen Lääketieteen Säätiö
- Academy of Finland
- Jane ja Aatos Erkon Säätiö
- Sigrid Juséliuksen Säätiö
- Orionin Tutkimussäätiö
- Syöpäsäätiö
- Biocenter, University of Oulu