Table 3.
Studies on tumor budding as a histomorphological prognostic factor in adenocarcinoma of the esophagus.
| Reference | Tumor subtype | Stage | N | Treatment | Method for assessment of TuB | Low-grade/high-grade TB% | Correlation of high-grade TB with clinicopathological features (p < 0.05) | Outcome |
|---|---|---|---|---|---|---|---|---|
| Brown et al., 2010 (16) | AC/SCC | I–IV | Total: 356 69 SCC 287 AC | 241/356 Patients treated by primary resection 115/356 Patients received pre-operative CTX | Ueno et al., 2004 (22) H&E | 48.3/51.7 | T-stage, N-stage, poor tumor differentiation, circumferential resection margin involvement, higher overall TNM-stage, low inflammatory response. No separate analysis of SCC and AC was performed. | Low-grade TB: OS 31 months; high-grade TB: OS 15 months (p < 0.0001) Prognostic impact of TB is independent of histologic type (SCC, p = 0.021; AC, p = 0.0001), age, N-stage, overall stage |
| Thies et al., 2013 (17) | AC | I–IV | 86 | 86/86 Patients were treated by primary resection | Karamitopoulou et al., 2013 (25) PanCK | 60.5/39.5 | pT-stage, higher tumor grade, non-intestinal/diffuse histological subtype, higher rates of R1-resection | Survival analysis showed a trend to worse survival for high-grade TB (p = 0.15; ITB p = 0.13) |
| Nowak et al., 2013 (18) | AC | I | 42 | 42/42 Patients were treated by primary resection | Adapted Ueno et al., 2004 (22) H&E | Not specified | N-stage | High-grade TB was a strong predictor of tumor recurrence (HR = 14.21; p = 0.022) and reduced OS (HR = 3.06; p = 0.015) |
| Landau et al., 2014 (19) | AC | I esophageal AC or AC of gastro esophageal junction | 210 | 210/210 Patients were treated by primary resection | Ueno et al., 2004 (22) H&E adapted according to Ohike et al., 2010 (52) | Any TB: 44.3% focal: 16% extensive 28% no TB: 55.7% | N-stage, submucosal invasion depth, grade, angioinvasion, tumor size | 5-year OS: no TB: 79%, focal TB: 71%, extensive TB: 37% (p > 0.001) Multivariate analysis: HR for death (extensive TB): 3.3 (95% CI = 1.5–7.4, p = 0.004); independent of T- and N-stage, age, type of surgery |
| Disease recurrence at 24 months: no TB: 5%, focal TB: 19%, extensive TB: 36% | ||||||||
| Multivariate analysis: HR for recurrence (extensive TB): 3.3 (95% CI = 1.4–7.0, p = 0.005); independent of T- and N-stage |
TB, tumor budding; SCC, squamous cell carcinoma; AC, adenocarcinoma; CTX, chemotherapy; RTX, radiotherapy; H&E, hematoxylin and eosin; PanCK, pancytokeratin; V1, venous invasion; L1, lymphatic invasion; Pn1, perineural invasion; OS, overall survival.