Prognostic significance of tumor budding, desmoplastic reaction, and lymphocytic infiltration in patients with gastric adenocarcinoma

Table 1 Tumor budding, desmoplastic reaction and tumor-infiltrating lymphocytes in relation to clinicopathological parameters in the whole group

Parameters	n	PTB1 (%)	PTB2 (%)	PTB3 (%)	ITB1 (%)	ITB2 (%)	ITB3 (%)	DR1 (%)	DR2 (%)	DR3 (%)	TILs (%)	TILs (%)
Age, yr
< 62.14 ± 12.00	64	11 (42.3)	25 (59.5)	28 (45.2)	15 (48.4)	14 (56.0)	35 (47.3)	29 (50.0)	20 (52.6)	15 (44.1)	34 (50.0)	30 (48.4)
≥ 62.14 ± 12.00	66	15 (57.7)	17 (40.5)	34 (54.8)	16 (51.6)	11 (44.0)	39 (52.7)	29 (50.0)	18 (47.4)	19 (55.9)	34 (50.0)	32 (51.6)
Gender
Male	77	16 (61.5)	26 (61.9)	35 (56.5)	18 (58.1)	19 (76.0)	40 (54.1)	43 (74.1)	23 (60.5)	11 (32.4)a	36 (52.9)	41 (66.1)
Female	53	10 (38.5)	16 (38.1)	27 (43.5)	13 (41.9)	6 (24.0)	34 (45.9)	15 (25.9)	15 (39.5)	23 (67.6)	32 (47.1)	21 (33.9)
Diameter
< 1.86 ± 1.02	84	16 (61.5)	29 (69.0)	39 (62.9)	16 (51.6)	19 (76.0)	49 (66.2)	34 (58.6)	28 (73.7)	22 (64.7)	47 (69.1)	37 (59.7)
≥ 1.86 ± 1.02	46	10 (38.5)	13 (31.0)	23 (37.1)	15 (48.4)	6 (24.0)	25 (33.8)	24 (41.4)	10 (26.3)	12 (35.3)	21 (30.9)	25 (40.3)
Invasion
T1	7	5 (19.2)	2 (4.8)	0b	4 (12.9)	1 (4.0)	2 (2.7)	3 (5.2)	3 (7.9)	1 (2.9)	4 (5.9)	3 (4.8)
T2	39	4 (15.4)	15 (35.7)	20 (32.3)	12 (38.7)	8 (32.0)	19 (25.7)	22 (37.9)	9 (23.7)	8 (23.5)	18 (26.5)	21 (33.9)
T3	52	11 (42.3)	15 (35.7)	26 (41.9)	10 (32.3)	6 (24.0)	36 (48.6)	25 (43.1)	16 (42.1)	11 (32.4)	27 (39.7)	25 (40.3)
T4	32	6 (23.1)	10 (23.8)	16 (25.8)	5 (16.1)	10 (40.0)	17 (23.0)	8 (13.8)	10 (26.3)	14 (41.2)	19 (27.9)	13 (21.0)
LNM
Absent	82	23 (88.5)	29 (69.0)	30 (48.4)a	29 (93.5)	16 (64.0)	37 (50.0)a	43 (74.1)	23 (60.5)	16 (47.1)c	38 (55.9)	44 (71.0)
Present	48	3 (11.5)	13 (31.0)	32 (51.6)	2 (6.5)	9 (36.0)	37 (50.0)	15 (25.9)	15 (39.5)	18 (52.9)	30 (44.1)	18 (29.0)
Metastasis
Absent	106	26 (100.0)	31 (73.8)	49 (79.0)c	21 (67.7)	23 (92.0)	62 (83.8)	49 (84.5)	33 (86.8)	24 (70.6)	55 (80.9)	51 (82.3)
Present	24	-	11 (26.2)	13 (21.0)	10 (32.3)	2 (8.0)	12 (16.2)	9 (15.5)	5 (13.2)	10 (29.4)	13 (19.1)	11 (17.7)
Stage
I	21	11 (42.3)	9 (21.4)	1 (1.6)a	10 (32.3)	6 (24.0)	5 (6.8)a	13 (22.4)	6 (15.8)	2 (5.9)	13 (19.1)	8 (12.9)
II	38	6 (23.1)	12 (28.6)	20 (32.3)	8 (25.8)	4 (16.0)	26 (35.1)	20 (34.5)	11 (28.9)	7 (20.6)	18 (26.5)	20 (32.3)
III	48	8 (30.8)	11 (26.2)	29 (46.8)	3 (9.7)	14 (56.0)	31 (41.9)	16 (27.6)	15 (39.5)	17 (50.0)	24 (35.3)	24 (38.7)
IV	23	1 (3.8)	10 (23.8)	12 (19.4)	10 (32.3)	1 (4.0)	12 (16.2)	9 (15.5)	6 (15.8)	8 (23.5)	13 (19.1)	10 (16.1)
Subtype
Intestinal	100	24 (92.4)	39 (92.9)	37 (59.7)a	30 (96.8)	21 (84.0)	49 (66.2)b	47 (81.0)	28 (73.7)	25 (73.5)	52 (76.5)	48 (77.4)
Diffuse	19	1 (3.8)	3 (7.1)	15 (24.2)	1 (3.2)	2 (8.0)	16 (21.6)	8 (13.8)	4 (10.5)	7 (20.6)	10 (17.7)	9 (14.5)
Mixed	11	1 (3.8)	0	10 (16.1)	0	2 (8.0)	9 (12.2)	3 (5.2)	6 (15.8)	2 (5.9)	6 (8.8)	5 (8.1)
LVI
Absent	89	14 (53.8)	28 (66.7)	47 (75.8)	16 (51.6)	19 (76.0)	54 (73.0)	39 (67.2)	24 (63.2)	26 (76.5)	45 (66.2)	44 (71.0)
Present	41	12 (46.2)	14 (33.3)	15 (24.2)	15 (48.4)	6 (24.0)	20 (27.0)	19 (32.8)	14 (36.8)	8 (23.5)	23 (33.8)	18 (29.0)
PNI
Absent	94	16 (61.5)	28 (66.7)	50 (80.6)	18 (58.1)	19 (76.0)	57 (77.0)	43 (74.1)	25 (65.8)	26 (76.5)	52 (76.5)	42 (67.7)
Present	36	10 (38.5)	14 (33.3)	12 (19.4)	13 (49.0)	6 (24.0)	11 (23.0)	15 (25.9)	13 (34.2)	8 (23.5)	16 (23.5)	20 (32.3)
Survival
Deceased	100	9 (34.6)	29 (69.0)	62 (100.0)a	8 (25.8)	20 (80.0)	72 (97.3)a	40 (69.0)	29 (76.3)	31 (91.2)	56 (82.4)	44 (71.0)
Alive	30	17 (65.4)	13 (31.0)	0	23 (74.2)	5 (20.0)	2 (2.7)	18 (31.0)	9 (23.7)	3 (8.8)	12 (17.6)	18 (29.0)
PTB
PTB1	26	-	-	-	17 (54.8)	3 (12.0)	6 (8.1)a	15 (25.9)	8 (21.1)	3 (8.8)d	10 (14.7)	16 (25.8)b
PTB2	42	-	-	-	14 (45.2)	18 (72.0)	10 (13.5)	24 (41.4)	12 (31.6)	6 (17.7)	17 (25.0)	25 (40.3)
PTB3	62	-	-	-	0	4 (16.0)	58 (78.4)	19 (32.8)	18 (47.4)	25 (73.5)	41 (60.3)	21 (33.9)
ITB
ITB1	31	-	-	-	-	-	-	21 (36.2)	8 (21.1)	2 (5.9)d	9 (13.2)	22 (35.5)d
ITB2	25	-	-	-	-	-	-	13 (22.4)	6 (15.8)	6 (17.6)	13 (19.2)	12 (19.4)
ITB3	74	-	-	-	-	-	-	24 (41.4)	24 (63.2)	26 (76.5)	46 (67.6)	28 (45.1)
DR
DR1	58	-	-	-	-	-	-	-	-	-	22 (32.4)	36 (58.0)b
DR2	38	-	-	-	-	-	-	-	-	-	24 (35.2)	14 (22.6)
DR3	34	-	-	-	-	-	-	-	-	-	22 (32.4)	12 (19.4)

^aP < 0.001.

^bP < 0.01.

^cP < 0.05.

^dP < 0.01.

N: Number of cases; PTB: Peritumoral budding; ITB: Intra-tumoral budding; DR: Desmoplastic reaction; TILs: Tumor-infiltrating lymphocytes; LVI: Lymphovascular invasion; PNI: Perineural invasion; LNM: Lymph node metastasis.

Table 2 Clinicopathological parameters associated with survival in all cases and patients with intestinal tumors (Log-rank test)

Parameters	All cases		Intestinal tumors
	mean ± SE (95%CI)	Median ± SE (95%CI)	mean ± SE (95%CI)	Median ± SE (95%CI)
Age
< 62.14 ± 12.00	48.2 ± 4.5 (39.4-56.9)	37.0 ± 1.1 (34.8-39.1)	53 ± 5.9 (41.4-64.5)	36.0 ± 1.2 (33.4-38.5)
≥ 62.14 ± 12.00	50.8 ± 4.8 (41.3-60.3)	39.0 ± 9.5 (20.1-57.8)	55.7 ± 5.7 (44.4-66.9)	60.0 ± 16.2 (28.2-91.7)
Gender
Male	50.1 ± 4.7 (41.3-59.0)	36.0 ± 2.6 (30.8-41.1)	54.7 ± 5.5 (43.7-65.6)	38.0 ± 3.3 (31.5-44.5)
Female	44.9 ± 5.2 (39.1-58.7)	38.0 ± 1.6 (34.9-41.0)	54.5 ± 6.3 (42-67.1)	38.0 ± 9.6 (19.1-56.8)
Diameter
< 1.86 ± 1.02	47.3 ± 3.7 (40.0-54.6)	38.0 ± 1.8 (3.4-41.5)	50.2 ± 4.5 (41.3-59.1)	38.0 ± 2.7 (32.6-43.3)
≥ 1.86 ± 1.02	52.3 ± 6.3 (39.8-64.7)	36.0 ± 4.6 (26.8-45.1)	61.4 ± 8.2 (45.2-77.6)	38.0 ± 13.4 (11.6-64.3)
Invasion
T1	65.1 ± 7.1 (51.2-79.1)	78.0 ± 22.1 (34.5-121.4)	65.1 ± 7.1 (51.1-79.1)	78.0 ± 22.1 (34.5-121.4)
T2	54.5 ± 6.6 (41.5-67.5)	38.0 ± 2.6 (32.9-43.0)	63.5 ± 8.6 (46.6-80.4)	52.0 ± 14.4 (23.7-80.2)
T3	44.8 ± 4.8 (35.4-54.3)	36.0 ± 4.3 (27.5-44.5)	46.4 ± 5.7 (35-57.7)	35.0 ± 5.5 (241.0-45.8)
T4	44.0 ± 5.4 (32.3-53.6)	30.0 ± 2.8 (24.4- 35.5)	48.7 ± 7.0 (35-62.5)	36.0 ± 3.1 (29.7-42.2)
LNM
Absent	51.6 ± 4.8 (52.1-71.0)	46.0 ± 5.5 (35.1-56.8)a	66.1 ± 5.5 (55.3-77.1)	62.0 ± 13.2 (35.8-88.1)a
Present	30.6 ± 3.0 (24.6-36.6)	24.0 ± 2.2 (19.5-28.4)	32.1 ± 4.5 (23.3-40.8)	24.0 ± 7.7 (8.7-39.2)
Metastasis
Absent	48.3 ± 3.2 (41.9-54.8)	38.0 ± 1.5 (34.9-41.0)	53.4 ± 4.1 (45.2-61.6)	39.0 ± 4.8 (29.4-48.5)
Present	51.7 ± 9.7 (32.6-70.7)	24.0 ± 8.3 (7.6-40.3)	55.1 ± 10.8 (33.8-76.5)	36.0 ± 12.0 (12.4-59.5)
Stage
I	69.1 ± 6.9 (55.5-82.7)	72.0 ± 11.1 (50.3-93.6)b	71.5 ± 6.8 (58.1-85.1)	72.0 ± 10.9 (50.5-93.4)c
II	45.1 ± 5.3 (34.7-55.5)	37.0 ± 2.2 (32.6-41.3)	52.3 ± 7.2 (38.1-66.5)	39.0 ± 2.5 (34.0-43.9)
III	38.6 ± 3.9 (30.8-46.4)	33.0 ± 3.4 (26.2-39.7)	40.0 ± 5.8 (28.5-51.4)	29.0 ± 4.9 (19.2-38.7)
IV	31.3 ± 10.8 (37.1-59.5)	30.0 ± 12.3 (11.8-60.1)	38.3 ± 10.8 (27.1-48.7)	30.0 ± 12.3 (29.8-42.1)
Subtype
Intestinal	55.1 ± 4.4 (46.6-63.7)	38.0 ± 2.7 (32.9-42.1)d	-	-
Not intestinal	32.5 ± 2.2 (18.8-36.7)	30.0 ± 1.2 (6.2-17.7)	-	-
Grade
Low	-	-	61.9 ± 5.7 (50.6-73.2)	52.0 ± 11.6 (29.1-74.8)
Moderate	-	-	49.9 ± 10.6 (29.0-70.8)	32.0 ± 4.7 (22.7-41.2)
High	-	-	43.2 ± 6.8 (29.9-56.5)	29.0 ± 12.3 (4.7-53.2)
LVI
Absent	54.3 ± 5.8 (43.0-65.7)	41.0 ± 2.2 (36.5-45.4)	59.0 ± 6.9 (45.4-72.7)	41.0 ± 7.0 (27.0-54.9)
Present	46.6 ± 4.0 (38.6-54.6)	36.0 ± 3.4 (29.1-42.8)	51.4 ± 5.1 (41.2-61.5)	36.0 ± 2.9 (30.2-41.7)
PNI
Absent	55.2 ± 6.5 (42.5-67.9)	38.0 ± 3.9 (30.2-45.7)	60.4 ± 7.7 (45.3-75.5)	38.0 ± 9.8 (18.6-57.3)
Present	46.9 ± 3.8 (39.4-54.4)	36.0 ± 2.2 (31.6-40.3)	51.7 ± 4.8 (42.3-61.2)	38.0 ± 2.5 (33-42.9)
PTB
PTB1	88.3 ± 5.2 (78.0-98.6)	73.5 ± 12.7 (71.6-92.5)a	92.4 ± 4.7 (83.3-101.9)	88.2 ± 7.6 (56.9-91.6)a
PTB2	61.8 ± 6.4 (48.6-73.6)	38.0 ± 2.8 (33.5-42.5)	63.0 ± 6.5 (50.2-75.8)	41.0 ± 3.1 (34.8-47.1)
PTB3	26.7 ± 2.4 (21.9-31.5)	22.0 ± 1.5 (19.1-24.9)	22.7 ± 3.6 (15.6-29.8)	16.0 ± 2.1 (33.8-42.1)
ITB
ITB1	101.1 ± 6.7 (87.8-114.4)	91.2 ± 5.2 (81.4-112.5)a	103.8 ± 6.4 (91.1-116.4)	63.0 ± 8.3 (88.7-97.4)a
ITB2	47.7 ± 4.6 (38.6-56.7)	41.0 ± 4.2 (32.8-49.2)	50.1 ± 5.2 (39.9-60.2)	42.0 ± 6.3 (29.0-52.9)
ITB3	29.9 ± 2.4 (25.3-34.6)	26.0 ± 1.9 (22.2-29.8)	28.5 ± 3.4 (21.8-35.2)	22.0 ± 4.0 (13.9-30.0)
DR
DR1	60.4 ± 5.4 (49.8-70.9)	41.0 ± 7.9 (25.4-56.6)d	67.2 ± 6.2 (55.1-79.3)	72.0 ± 18.1 (36.4-107.5)a
DR2	48.0 ± 6.6 (35.1-61.0)	36.0 ± 4.5 (27.3-44.8)	53.5 ± 8.4. (36.9-70.1)	38.0 ± 9.1 (20.0-55.9)
DR3	27.0 ± 4.1 (18.8-35.2)	18.0 ± 3.6 (10.8-25.1)	31.8 ± 5.3 (21.3-42.2)	24.0 ± 6.7 (10.9-37.0)
TILs
TILs	53.8 ± 4.3 (45.3-62.4)	39.0 ± 4.8 (29.4-48.5)	59.6 ± 5.2 (49.3-70.0)	53.0 ± 14.7 (24.0-81.9)
TILs	43.9 ± 4.6 (34.9-52.9)	35.0 ± 4.5 (26.2-43.7)	47.8 ± 5.7 (36.5-59.1)	35.0 ± 5.1 (24.9-45.0)

^aP < 0.001.

^bP < 0.01.

^cP < 0.05.

^dP < 0.01.

SE: Standard error; CI: Confidence interval; LNM: Lymph node metastasis; LVI: Lymphovascular invasion; PNI: Perineural invasion: PTB: Peritumoral budding; ITB: Intratumoral budding; DR: Desmoplastic reaction; TILs: Tumor-infiltrating lymphocytes.

Table 3 Multivariate analysis including parameters associated with prognosis in the Log-rank test in the entire group and tumors of the intestinal subtype

Parameters	All group			P value	Intestinal tumors			P value
	HR	Lower (95%CI)	Upper (95%CI)		HR	Lower (95%CI)	Upper (95%CI)
ITB	2.06	1.40	3.01	< 0.001	3.32	2.34	4.72	< 0.001
PTB	1.83	1.29	2.59	< 0.001	2.01	1.32	3.05	< 0.001
LNM	1.53	1.00	2.33	0.04	1.09	0.59	2.04	0.760
Stage	1.06	0.81	1.40	0.63	1.12	0.80	1.58	0.480
Subtype	0.76	0.50	1.17	0.22	-	-	-	-
DR	1.11	0.87	1.42	0.39	1.17	0.86	1.60	0.290

HR: Hazard ratio; CI: Confidence interval; LNM: Lymph node metastasis; PTB: Peritumoral budding; ITB: Intratumoral budding; DR: Desmoplastic reaction; TILs: Tumor infiltrating lymphocytes.

Table 4 Tumor budding, desmoplastic reaction, and tumor-infiltrating lymphocytes in relation to clinicopathological parameters in the intestinal group

Parameters	n	PTB1 (%)	PTB2 (%)	PTB3 (%)	ITB1 (%)	ITB2 (%)	ITB3 (%)	DR1 (%)	DR2 (%)	DR3 (%)	TILs (%)	TILs (%)
Age, yr		24	39	37	30	21	49	47	28	25	52	48
< 62.14 ± 12.00	47	10 (41.7)	24 (61.5)	13 (35.1)	14 (46.7)	11 (52.4)	22 (44.9)	21 (44.7)	15 (53.6)	11 (44.0)	25 (48.1)	22 (45.8)
≥ 62.14 ± 12.00	53	14 (58.3)	15 (38.5)	24 (63.9)	16 (53.3)	10 (47.6)	27 (55.1)	26 (55.3)	13 (46.4)	14 (56.0)	27 (51.9)	26 (54.2)
Gender
Male	60	15 (62.5)	24 (61.5)	21 (56.8)	18 (60.0)	15 (71.4)	27 (55.1)	34 (72.3)	16 (57.1)	10 (40.0)a	27 (51.9)	33 (68.8)
Female	40	9 (37.5)	15 (38.5)	16 (43.2)	12 (40.0)	6 (28.6)	22 (44.9)	13 (27.7)	12 (42.9)	15 (60.0)	25 (48.1)	15 (31.3)
Diameter
< 1.86 ± 1.02	67	16 (66.7)	26 (66.7)	25 (67.6)	15 (50.0)	16 (76.2)	36 (73.5)	28 (59.6)	22 (78.6)	17 (68.0)	38 (73.1)	29 (60.4)
≥ 1.86 ± 1.02	33	8 (33.3)	13 (33.3)	12 (32.4)	15 (50.0)	5 (23.8)	13 (26.5)	19 (40.4)	6 (21.4)	8 (32.0)	14 (26.9)	19 (39.6)
Invasion
T1	7	5 (20.8)	2 (5.1)	0	4 (13.3)	1 (4.8)	2 (4.1)	3 (6.4)	3 (10.7)	1 (4.0)	4 (7.7)	3 (6.3)
T2	28	4 (16.7)	15 (38.5)	9 (24.3)	12 (40.0)	7 (33.3)	9 (18.4)	14 (29.8)	9 (32.1)	5 (20.0)	12 (23.1)	16 (33.3)
T3	42	10 (41.7)	13 (33.3)	19 (51.4)	9 (30.0)	6 (28.6)	27 (55.1)	23 (48.9)	12 (42.9)	7 (28.0)	23 (44.2)	19 (39.6)
T4	23	5 (20.8)	9 (23.1)	9 (24.3)	5 (16.7)	7 (33.3)	11 (22.4)	7 (14.9)	4 (14.3)	12 (48.0)	13 (25.0)	10 (20.8)
LNM
Absent	69	22 (91.7)	29 (74.4)	18 (48.6)b	29 (96.7)	14 (66.7)	26 (53.1)b	39 (83.0)	19 (67.9)	11 (44.0)c	32 (61.5)	37 (77.1)
Present	31	2 (8.3)	10 (25.6)	19 (51.4)	1 (3.3)	7 (33.3)	23 (46.9)	8 (17.0)	9 (32.1)	14 (56.0)	20 (38.5)	11 (22.9)
Metastasis
Absent	79	24 (100.0)	29 (74.4)	26 (70.3)d	21 (70.0)	20 (95.2)	38 (77.6)	39 (83.0)	23 (82.1)	17 (68.0)	40 (76.9)	39 (81.3)
Present	21	0	10 (25.6)	11 (29.7)	9 (30.0)	1 (4.8)	11 (22.4)	8 (17.0)	5 (17.9)	8 (32.0)	12 (23.1)	9 (18.7)
Stage
I	20	11 (45.8)	9 (23.2)	0	10 (33.3)	5 (23.8)	5 (10.2)c	12 (25.5)	6 (21.4)	2 (8.0)	12 (23.1)	8 (16.7)
II	26	6 (25.0)	10 (25.6)	10 (27.0)	7 (23.3)	4 (19.0)	15 (30.6)	15 (31.9)	9 (32.1)	2 (8.0)	12 (23.1)	14 (29.3)
III	32	6 (25.0)	10 (25.6)	16 (43.2)	3 (10.0)	11 (52.4)	18 (36.7)	12 (25.5)	7 (25.0)	13 (52.0)	15 (28.8)	17 (35.2)
IV	22	1 (4.2)	10 (25.6)	11 (29.7)	10 (33.4)	1 (4.8)	11 (22.4)	8 (17.0)	6 (21.4)	8 (32.0)	13 (25.0)	9 (18.8)
Grade
Low	54	19 (79.2)	21 (53.8)	14 (37.8)a	22 (73.3)	12 (57.1)	20 (40.8)a	28 (59.6)	16 (57.1)	10 (40.0)	29 (55.8)	25 (52.1)
Moderate	29	2 (8.3)	13 (33.4)	14 (37.8)	3 (10.0)	6 (28.6)	20 (40.8	11 (23.4)	10 (35.7)	8 (32.0)	15 (28.8)	14 (29.2)
High	17	3 (12.5)	5 (12.8)	9 (24.3)	5 (16.7)	3 (14.3)	9 (18.4)	8 (17.0)	2 (7.2)	7 (28.0)	8 (15.4)	9 (18.7)
LVI
Absent	67	13 (54.2)	26 (66.7)	28 (75.7)	15 (50.0)	15 (71.4)	37 (75.5)	34 (72.3)	14 (50.0)	19 (76.0)	32 (61.5)	35 (72.9)
Present	33	11 (45.8)	13 (33.3)	9 (24.3)	15 (50.0)	6 (28.6)	12 (24.5)	13 (27.7)	14 (50.0)	6 (24.0)	20 (38.5)	13 (27.1)
PNI
Absent	71	14 (58.3)	26 (66.7)	31 (83.8)	18 (60.0)	15 (71.4)	38 (77.6)	34 (72.3)	16 (57.1)	21 (84.0)	37 (71.2)	34 (70.8)
Present	29	10 (41.7)	13 (33.3)	6 (16.2)	12 (40.0)	6 (28.6)	11 (22.4)	13 (27.7)	12 (42.9)	4 (16.0)	15 (28.8)	14 (29.2)
Survival
Deceased	71	7 (29.2)	27 (69.2)	37 (100.0)b	7 (23.3)	16 (76.2)	48 (98.0)b	29 (61.7)	20 (71.4)	22 (88.0)	41 (78.8)	30 (62.5)
Alive	29	17 (70.8)	12 (30.8)	0	23 (76.7)	5 (23.8)	1 (2.0)	18 (38.3)	8 (28.6)	3 (12.0)	11 (21.2)	18 (37.5)
PTB
PTB1	24	-	-	-	17 (56.7)	3 (14.3)	4 (8.2)b	14 (29.8)	8 (28.6)	2 (8.0)c	10 (19.2)	14 (29.2)d
PTB2	39	-	-	-	13 (43.3)	18 (85.7)	8 (16.3)	23 (48.9)	11 (39.3)	5 (20.0)	16 (30.8)	23 (47.9)
PTB3	37	-	-	-	0	0	37 (75.5)	10 (21.3)	9 (32.1)	18 (72.0)	26 (50.0)	11 (22.9)
ITB
ITB1	30	-	-	-	-	-	-	21 (44.7)	8 (28.6)	1 (4.0)c	9 (17.3)	21 (43.8)c
ITB2	21	-	-	-	-	-	-	12 (25.5)	3 (10.7)	6 (24.0)	9 (17.3)	12 (25.0)
ITB3	49	-	-	-	-	-	-	14 (29.8)	17 (60.7)	18 (72.0)	34 (65.4)	15 (31.2)
DR
DR1	47	-	-	-	-	-	-	-	-	-	17 (32.7)	30 (62.5)d
DR2	28	-	-	-	-	-	-	-	-	-	17 (32.7)	11 (22.9)
DR3	25	-	-	-	-	-	-	-	-	-	18 (34.6)	7 (14.6)

^aP < 0.05.

^bP < 0.001.

^cP < 0.008.

^dP < 0.01.

N: Number of cases; PTB: Peritumoral budding; ITB: Intratumoral budding; DR: Desmoplastic reaction; TILs: Tumor-infiltrating lymphocytes; LNM: Lymph node metastasis.