Significance of mucin-suspended tumor bud-like structures in colorectal cancer

Ville K. Äijälä; Päivi Sirniö; Hanna Elomaa; Henna Karjalainen; Meeri Kastinen; Vilja V. Tapiainen; Maarit Ahtiainen; Olli Helminen; Erkki Ville Wirta; Jukka Rintala; Sanna Meriläinen; Juha Saarnio; Tero Rautio; Toni T. Seppälä; Jan Böhm; Jukka Pekka Mecklin; Anne Tuomisto; Markus J. Mäkinen; Juha P. Väyrynen

doi:10.1016/j.humpath.2025.105772

Significance of mucin-suspended tumor bud-like structures in colorectal cancer

Ville K. Äijälä, Päivi Sirniö, Hanna Elomaa, Henna Karjalainen, Meeri Kastinen, Vilja V. Tapiainen, Maarit Ahtiainen, Olli Helminen, Erkki Ville Wirta, Jukka Rintala, Sanna Meriläinen, Juha Saarnio, Tero Rautio, Toni T. Seppälä, Jan Böhm, Jukka Pekka Mecklin, Anne Tuomisto, Markus J. Mäkinen, Juha P. Väyrynen

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Abstract

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 mm²) 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_trend = 0.0007; Cohort 2: HR 1.35, 95 % CI 0.98–1.85, p_trend = 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_trend = 0.006; Cohort 2: HR 1.39, 95 % CI 1.02–1.89, p_trend = 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.

Original language	English
Article number	105772
Journal	HUMAN PATHOLOGY
Volume	158
DOIs	https://doi.org/10.1016/j.humpath.2025.105772
Publication status	Published - Apr 2025
Publication type	A1 Journal article-refereed

Keywords

Colorectal cancer
Mucin
Prognosis
Tumor budding

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Pathology and Forensic Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.humpath.2025.105772Licence: CC BY

1-s2.0-S0046817725000590-mainFinal published version, 3.76 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202505085042Licence: CC BY

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Äijälä, V. K., Sirniö, P., Elomaa, H., Karjalainen, H., Kastinen, M., Tapiainen, V. V., Ahtiainen, M., Helminen, O., Wirta, E. V., Rintala, J., Meriläinen, S., Saarnio, J., Rautio, T., Seppälä, T. T., Böhm, J., Mecklin, J. P., Tuomisto, A., Mäkinen, M. J., & Väyrynen, J. P. (2025). Significance of mucin-suspended tumor bud-like structures in colorectal cancer. HUMAN PATHOLOGY, 158, Article 105772. https://doi.org/10.1016/j.humpath.2025.105772

@article{a76c3983597946a997e9fc0aba94ccca,

title = "Significance of mucin-suspended tumor bud-like structures in colorectal cancer",

abstract = "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 mm2) 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, ptrend = 0.0007; Cohort 2: HR 1.35, 95 \% CI 0.98–1.85, ptrend = 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, ptrend = 0.006; Cohort 2: HR 1.39, 95 \% CI 1.02–1.89, ptrend = 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.",

keywords = "Colorectal cancer, Mucin, Prognosis, Tumor budding",

author = "{\"A}ij{\"a}l{\"a}, \{Ville K.\} and P{\"a}ivi Sirni{\"o} and Hanna Elomaa and Henna Karjalainen and Meeri Kastinen and Tapiainen, \{Vilja V.\} and Maarit Ahtiainen and Olli Helminen and Wirta, \{Erkki Ville\} and Jukka Rintala and Sanna Meril{\"a}inen and Juha Saarnio and Tero Rautio and Sepp{\"a}l{\"a}, \{Toni T.\} and Jan B{\"o}hm and Mecklin, \{Jukka Pekka\} and Anne Tuomisto and M{\"a}kinen, \{Markus J.\} and V{\"a}yrynen, \{Juha P.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = apr,

doi = "10.1016/j.humpath.2025.105772",

language = "English",

volume = "158",

journal = "HUMAN PATHOLOGY",

issn = "0046-8177",

publisher = "Elsevier",

}

Äijälä, VK, Sirniö, P, Elomaa, H, Karjalainen, H, Kastinen, M, Tapiainen, VV, Ahtiainen, M, Helminen, O, Wirta, EV, Rintala, J, Meriläinen, S, Saarnio, J, Rautio, T, Seppälä, TT, Böhm, J, Mecklin, JP, Tuomisto, A, Mäkinen, MJ & Väyrynen, JP 2025, 'Significance of mucin-suspended tumor bud-like structures in colorectal cancer', HUMAN PATHOLOGY, vol. 158, 105772. https://doi.org/10.1016/j.humpath.2025.105772

TY - JOUR

T1 - Significance of mucin-suspended tumor bud-like structures in colorectal cancer

AU - Äijälä, Ville K.

AU - Sirniö, Päivi

AU - Elomaa, Hanna

AU - Karjalainen, Henna

AU - Kastinen, Meeri

AU - Tapiainen, Vilja V.

AU - Ahtiainen, Maarit

AU - Helminen, Olli

AU - Wirta, Erkki Ville

AU - Rintala, Jukka

AU - Meriläinen, Sanna

AU - Saarnio, Juha

AU - Rautio, Tero

AU - Seppälä, Toni T.

AU - Böhm, Jan

AU - Mecklin, Jukka Pekka

AU - Tuomisto, Anne

AU - Mäkinen, Markus J.

AU - Väyrynen, Juha P.

PY - 2025/4

Y1 - 2025/4

N2 - 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 mm2) 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, ptrend = 0.0007; Cohort 2: HR 1.35, 95 % CI 0.98–1.85, ptrend = 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, ptrend = 0.006; Cohort 2: HR 1.39, 95 % CI 1.02–1.89, ptrend = 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.

AB - 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 mm2) 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, ptrend = 0.0007; Cohort 2: HR 1.35, 95 % CI 0.98–1.85, ptrend = 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, ptrend = 0.006; Cohort 2: HR 1.39, 95 % CI 1.02–1.89, ptrend = 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.

KW - Colorectal cancer

KW - Mucin

KW - Prognosis

KW - Tumor budding

U2 - 10.1016/j.humpath.2025.105772

DO - 10.1016/j.humpath.2025.105772

M3 - Article

AN - SCOPUS:105002556282

SN - 0046-8177

VL - 158

JO - HUMAN PATHOLOGY

JF - HUMAN PATHOLOGY

M1 - 105772

ER -

Significance of mucin-suspended tumor bud-like structures in colorectal cancer

Abstract

Keywords

Publication forum classification

ASJC Scopus subject areas

UN SDGs

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