Department of Surgery, The University of Kentucky, Lexington.
The Markey Cancer Center, The University of Kentucky, Lexington.
JAMA Netw Open. 2021 Apr 1;4(4):e213897. doi: 10.1001/jamanetworkopen.2021.3897.
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.
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.
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).
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).
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.
肥胖与结直肠癌（CRC）风险增加和疾病进程更具侵袭性有关。肿瘤芽（TB）是 CRC 的一个重要预后因素，但它与肥胖的关系尚不清楚。
评估 TB 与肥胖和结肠癌其他预后因素的关系。
设计、地点和参与者：本队列研究对肯塔基大学医学中心 7 年内（2008 年 1 月至 2015 年 12 月）获得的结肠癌标本进行了组织学回顾；数据分析于 2020 年 2 月至 2021 年 1 月进行。标本来自 200 名 I 期至 III 期结肠癌患者；排除了 0 期、IV 期或数据不完整的患者。
TB 定义为肿瘤浸润边缘有 1 至 4 个恶性细胞，由 2 位学术病理学家独立评估。主要结局是 TB 与肥胖（定义为 BMI 为 30 或更高）的关系。次要结局包括 TB 与临床特征（即年龄、种族、性别、TNM 分期、肿瘤位置）和病理特征（即低分化肿瘤簇[PDCs]、Klintrup-Mäkinen 炎症评分、间质增生、浸润性肿瘤边界、肿瘤坏死和肿瘤-基质比）的关系。
共回顾了 200 个标本。患者的中位（四分位间距）年龄为 62（55-72）岁，102 名（51.0%）为女性，平均（SD）BMI 为 28.5（8.4）。其中 57 个标本（28.5%）来自 I 期肿瘤；74 个（37.0%）来自 II 期；69 个（34.5%）来自 III 期。其中，97 个（48.5%）为低级别（<5 个芽），36 个（18.0%）为中级别（5-9 个芽），67 个（33.5%）为高级别（≥10 个芽）TB。多变量分析调整了临床和组织学因素后，显示 TB 分级较高与肥胖（比值比[OR]，4.25；95%CI，1.95-9.26）、较高的 PDC 分级（2 级比 1 级：OR，9.14；95%CI，3.49-23.93；3 级比 1 级：OR，5.10；95%CI，2.30-11.27）、浸润性肿瘤边界增加（OR，1.03；95%CI，1.01-1.04）、盲肠位置（OR，2.55；95%CI，1.09-5.97）和较高的分期（例如，III 期比 I 期，高级别或中级别比低级别 TB：OR，2.91；95%CI，1.00-8.49）相关。此外，TB 分级较高的患者总生存较差（中级别 vs 低级别 TB：风险比，2.20；95%CI，1.11-4.35；对数秩 P<.02；高级别 vs 低级别 TB：风险比，2.67；95%CI，1.45-4.90；对数秩 P<.001）。
在这项队列研究中，发现了 TB 分级与肥胖之间的一种新的关联。这种关联可能反映了一种全身性疾病（即肥胖）局部影响结肠癌的侵袭性生长（即高 TB）。
