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Abstract
Importance: Obesity is associated with increased risk of colorectal cancer (CRC) and a more aggressive disease course. Tumor budding (TB) is an important prognostic factor for CRC, but its association with obesity is unknown.
Objective: To evaluate the association of TB with obesity and other prognostic factors in colon cancer.
Design, Setting, and Participants: This cohort study involved a histological review of colon cancer specimens obtained during 7 years (January 2008 to December 2015) at the University of Kentucky Medical Center; data analysis was conducted from February 2020 to January 2021. Specimens came from 200 patients with stage I to III colon cancer; patients with stage 0, stage IV, or incomplete data were excluded.
Main Outcomes and Measures: TB was defined as 1 to 4 malignant cells at the invasive edge of the tumor, independently assessed by 2 academic pathologists. The primary outcome was the association of TB with obesity (defined as body mass index [BMI] of 30 or greater). Secondary outcomes include the association of TB with clinical features (ie, age, race, sex, TNM stage, tumor location) and pathological features (ie, poorly differentiated tumor clusters [PDCs], Klintrup-Mäkinen inflammatory score, desmoplasia, infiltrative tumor border, tumor necrosis, and tumor-to-stroma ratio).
Results: A total of 200 specimens were reviewed. The median (interquartile range) age of patients was 62 (55-72) years, 102 (51.0%) were women, and the mean (SD) BMI was 28.5 (8.4). A total of 57 specimens (28.5%) were from stage I tumors; 74 (37.0%), stage II; and 69 (34.5%), stage III. Of these, 97 (48.5%) had low-grade (< 5 > buds), 36 (18.0%) had intermediate-grade (5-9 buds), and 67 (33.5%) had high-grade (≥ 10 buds) TB. Multivariable analysis adjusting for clinical and histological factors demonstrated that higher TB grade was associated with obesity (odds ratio [OR], 4.25; 95% CI, 1.95-9.26), higher PDC grade (grade 2 vs 1: OR, 9.14; 95% CI, 3.49-23.93; grade 3 vs 1: OR, 5.10; 95% CI, 2.30-11.27), increased infiltrative tumor border (OR, 1.03; 95% CI, 1.01-1.04), cecal location (OR, 2.55; 95% CI, 1.09-5.97), and higher stage (eg, stage III vs stage I for high-grade or intermediate-grade vs low-grade TB: OR, 2.91; 95% CI, 1.00-8.49). Additionally, patients with a higher TB grade had worse overall survival (intermediate vs low TB: hazard ratio, 2.20; 95% CI, 1.11-4.35; log-rank P = .02; high vs low TB: hazard ratio, 2.67; 95% CI, 1.45-4.90; log-rank P < .001).
Conclusions and Relevance: In this cohort study, a novel association between high TB grade and obesity was found. The association could reflect a systemic condition (ie, obesity) locally influencing aggressive growth (ie, high TB) in colon cancer.
Document Type
Article
Publication Date
4-1-2021
Digital Object Identifier (DOI)
https://doi.org/10.1001/jamanetworkopen.2021.3897
Funding Information
This works was supported by grant NCI P30 CA177558 from the Markey Cancer Center.
Repository Citation
Gan, Tong; Schaberg, Kurt B.; He, Daheng; Mansour, Akila; Kapoor, Harit; Wang, Chi; Evers, B. Mark; and Bocklage, Therese J., "Association between Obesity and Histological Tumor Budding in Patients with Nonmetastatic Colon Cancer" (2021). Surgery Faculty Publications. 46.
https://uknowledge.uky.edu/surgery_facpub/46
Supplementary methods
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Notes/Citation Information
Published in JAMA Network Open, v. 4, issue 4, e213897.
© 2021 Gan T et al.
This is an open access article distributed under the terms of the CC-BY License.