Tumor budding in gastric cancer

Table 1 Previous studies on tumor budding in gastric cancer

Ref.	Country	Period	Cases	Lauren	Specimen	Staging	Assessment (%)	TB higher in	Outcomes (Multivariate analysis)
Gulluoglu et al[33], 2015	Turkey	1993-2013	126	I+D	Surgical resected	pT1a-1b	PTB, 400 ×; Positive/HPF (31)	LNM	LNM; pT1a: OR = 38.6 (1.91-781.70); pT1b: OR = 8.87 (2.79-22.16)
Che et al[68], 2017	China	2007-2010	296	I+D	Surgical resected	I-IV	PTB, 400 ×; ≥ 5 buds, on average 10 HFP (49)	T stage, N stage, metastasis, TNM stage, differentiation	OS: 1.568 (1.044-2.354)
Olsen et al[16], 2017	United States	1999-2013	52	I	Surgical resected	NA	Total-TB, 200 ×; ≥ 1 bud, median of 10 HFP (63)	Poor differentiation, LVI, PNI, T stage, N stage	Recurrence: P = 0.08; LNM: P = 0.51
Kemi et al[61], 2019	Finland	1983-2016	583	I+D	Surgical resected	I-IV	PTB, ITBCC; Bd1/2 (44.9), Bd3 (55.1)	Year of surgery, age, sex, T stage, Lauren class, grade; R	OS; Total: HR = 1.40 (1.12-1.76); I: HR = 1.39 (1.03-0.87); D: HR = 1.54 (1.01-1.2.34)
Du et al[34], 2019	China	2010-2016	621	I+D	Surgical resected	pT1b	PTB, 200 ×; ≥ 1 bud/HPF (67)	NA	LNM; Total: OR = 3.3 (1.9-5.9); Well/moderately differentiated: OR = 3.3 (1.9-5.9)
Heckl et al[69], 2019	Germany	1997-2009	426	I+D	Surgical resected	I-IV	PTB, ITBCC; Bd0 (24.9), Bd1/2 (22.8), Bd3 (52.3)	NA	NS
Dao et al[18], 2020	Vietnam	2012-2015	109	I+D	Surgical resected	I-III	PTB, ITBCC; Bd1/2 (54.1), Bd3 (45.9)	Histopathological type, Differentiated grade, Lauren class, LVI, PNI, N stage	OS, HR = 20.899, P < 0.001; DFS, HR = 12.7, P < 0.001
Ulase et al[13], 2020	Germany	1997-2009	456	I+D	Surgical resected	I-IV	PTB, ITBCC; Bd0 (25.2), Bd1/2 (22.8), Bd3 (52.0)	Sex, Lauren class, differentiated grade, T stage, N stage, metastasis, TNM stage, LNR, LVI, PNI, R, HER-2, MSI, MET	OS, Total, I, D: NS. TSS, Total, I: NS; D: NA
Zhang et al[25], 2020	China	2001-2003	147	I+D	Surgical resected	I-III	PTB, 200 ×; ≥ 6 buds, median of 5 HFP (46.3)	Tumor size, N stage, TNM stage, Lauren class, TILs	10-yr OS, HR = 7.16 (3.35-15.29)
Qi et al[57], 2020	China	2000-2008	153	I	Surgical resected	I-III	PTB and ITB, 400 ×; PTB: ≥ 8 buds, median of 5 HFP (48.4); ≥ 13 buds, median of 5 HFP (43.8)	PTB: Age, sex, location, N stage; ITB: Tumor size, N stage, TNM stage, grade	OS, PTB: HR = 1.92 (2.24-10.63); ITB: HR = 2.79 (2.24-10.63)
Cao et al[17], 2021	China	2009-2015	137	I+D	ESD and Surgical resected	pT1	PTB, NA; Positive (58.4)	Age, HP infection, N stage, recurrence, death	Recurrence, HR = 4.95, P = 0.01; Death, HR = 2.33, P = 0.043
Sun et al[21], 2021	China	2004-2007	122	I+D	Surgical resected	I-IV	PTB, 200 ×; > 5 buds, median of 10 HFP (57)	Lauren class, differentiation, LNM, metastasis, TNM stage	NA
Yim et al[32], 2021	Korea	2010-2021	289	I+D	Surgical resected	pT1	TB-YN: Present (57.1); TB-ITBCC: Bd2/3 (40.1); total-TB, ≥ 5 buds (419); SRCC excluded: mTB-YN: Present (48.8); mTB-ITBCC: Bd2/3 (29.1); total-mTB, ≥ 5 buds (29.8)	LNM	LNM, TB-YN: HR = 24.36 (3.15-188.17); TB-ITBCC: HR = 15.91 (5.41-46.80); Total-TB: HR = 25.50 (6.97-93.25); mTB-YN: HR = 21.07 (4.75-93.37); mTB-ITBCC: HR = 35.10 (12.11-101.76); Total-mTB: HR = 52.69 (15.69-179.97)
Kucuk[70], 2021	Turkey	2015-2020	43	I+D	Surgical resected	pT2-4	PTB, ITBCC; Bd1 (30.2), Bd2 (25.6), Bd3 (44.2)	Grade; T stage; N stage, differentiation	NA
Pun et al[15], 2022	Canada	2000-2018	76	I	Surgical resected	IA-IV	PTB, ITBCC; Bd1 (21), Bd2 (21), Bd3 (58)	T stage, LNM, TNM stage, LVI, PNI, death, recurrence	OS: HR = 3.93 (0.34-45.44)
Jesinghaus et al[43], 2022	Germany	2001-2013	167	I	Surgical resected	ypI-IV	PTB, ITBCC; Bd1 (29), Bd2 (25), Bd3 (46)	T stage, N stage, metastasis, TNM stage, R	OS: Bd2: HR = 2.60 (1.14-5.95); Bd3: HR = 4.74 (2.25-10.03)
Szalai et al[14], 2022	Hungary	2008-2018	290	I+D	Surgical resected	IA-IV	PTB, ITBCC; Bd0 (1), Bd1 (6.6), Bd2 (13.8), Bd3 (78.6)	Lauren class, R; PNI; LVI; T stage, TNM stage, differentiation, LNM	OS, Total: HR = 1.65 (1.11-2.45); I: HR = 1.99 (1.23-3.22). DFS, Total, I: NS

D: Diffuse; DFS: Disease-free survival; ESD: Endoscopic submucosal dissection; HPF: High power field; HR: Hazard ratio; I: Intestinal; ITB: Intratumoral budding; ITBCC: International Tumor Budding Consensus Conference; LNM: Lymph node metastasis; LNR: Lymph node ratio; LVI: Lymphovascular invasion; MSI: Microsatellite instability; NA: Not available; NS: No significance; OR: Odds ratio; OS: Overall survival; PNI: Perineural invasion; PTB: Peritumoral budding; R: Resection status; SRCC: Signet ring cancer cell; TB: Tumor budding; TILs: Tumor infiltrate lymphocytes; TSS: Tumor-specific survival.