Clinicopathologic factors and molecular markers related to lymph node metastasis in early gastric cancer

Table 1 Baseline characteristics of patients with early gastric cancer (n = 1104)

Characteristics	Value
Age (yr)
< 60	546 (49.5)
≥ 60	558 (50.5)
mean ± SD	58.49 ± 11.63
Gender
Male	709 (64.2)
Female	395 (35.8)
Size of tumor (mm)
< 20 mm	397 (34.3)
≥ 20 mm	725 (65.7)
mean ± SD	27.8 ± 17.8
Location
Upper third	125 (11.3)
Middle third	325 (29.4)
Lower third	654 (59.2)
Macroscopic type
Elevated (I, IIa, I + IIa, IIa + IIb)	86 (7.8)
Flat (IIb)	81 (7.3)
Depressed (IIc, III, IIb + III)	815 (73.8)
Mixed	122 (11.1)
Depth of invasion
Mucosa	625 (56.6)
Submucosa
Sm 1	150 (13.6)
Sm 2	157 (14.2)
Sm 3	172 (15.6)
Ulcer
Absent	958 (86.8)
Present	146 (13.2)
Lymphovascular invasion
Absent	955 (86.5)
Present	149 (13.5)
Histological type
Well differentiated	236 (21.4)
Moderate differentiated	398 (36.1)
Poorly differentiated	243 (22.0)
Signet ring cell	227 (20.6)
Lymph-node metastasis
Negative	1000 (90.6)
Positive	104 (9.4)

Data are expressed as absolute numbers (percentage) or mean ± SD. Sm1: Upper third; Sm2: Middle third; Sm3: Lower third.

Table 2 Molecular markers of patients with early gastric cancer n (%)

Molecular markers	Value
Microsatellite instability
MSS	909 (90.1)
MSI-L	31 (3.1)
MSI-H	69 (6.8)
hMLH1
Loss	48 (6.3)
Expression	716 (93.7)
p53
Negative	651 (62.2)
Positive	396 (37.8)
EGFR overexpression
Negative	613 (88.8)
Positive	77 (11.2)
HER2 overexpression
Negative	296 (72.9)
Positive	110 (27.1)

MSS: Microsatellite stable; MSI-L: Microsatellite instability-low; MSI-H: Microsatellite instability-high; hMLH1: Human mutL homolog 1; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2.

Table 3 Univariate analysis of potential risk factors for lymph node metastasis n (%)

Factor for lymph node metastasis	Presence (n = 104)	Absence (n = 1000)	P value
Age (yr)			0.049
< 60	61 (58.7)	485 (48.5)
≥ 60	43 (41.3)	515 (51.5)
Gender			0.003
Male	53 (51.0)	656 (65.6)
Female	51 (49.0)	344 (34.4)
Size of tumor (mm)			< 0.0001
< 20 mm	9 (8.7)	370 (37.0)
≥ 20 mm	95 (91.3)	630 (63.0)
Location			0.389
Upper third	9 (8.7)	116 (11.6)
Middle third	36 (34.6)	289 (28.9)
Lower third	59 (56.7)	595 (59.5)
Macroscopic type			< 0.0001
Elevated	7 (6.7)	78 (7.8)
Flat	1 (1.0)	80 (8)
Depressed	72 (69.2)	743 (74.3)
Mixed	24 (23.1)	98 (9.8)
Depth of invasion			< 0.0001
Mucosa	24 (23.1)	601 (60.1)
Submucosa	80 (77.0)	399 (39.9)
Sm1	11 (10.6)	139 (13.9)
Sm2	34 (32.7)	123 (12.3)
Sm3	35 (33.7)	137 (13.7)
Ulceration			0.222
Absent	86 (9.0)	872 (91.0)
Present	18 (12.1)	128 (85.9)
Lymphovascular invasion			< 0.0001
Absent	44 (42.3)	911 (91.1)
Present	60 (57.7)	89 (8.9)
Histological type			< 0.0001
Well differentiated	4 (3.8)	232 (23.2)
Moderate differentiated	45 (43.3)	352 (35.2)
Poorly differentiated	36 (34.6)	208 (20.8)
Signet ring cell	19 (18.3)	208 (20.8)

Sm1: Upper third; Sm2: Middle third; Sm3: Lower third.

Table 4 Univariate analysis of predictive molecular markers for lymph node metastasis n (%)

Lymph node metastasis	Presence	Absence	P value
Microsatellite instability			0.412
MSS	89 (90.8)	820 (90.0)
MSI-L	1 (1.0)	30 (3.3)
MSI-H	8 (8.2)	61 (6.7)
hMLH1			0.703
Negative	5 (7.4)	43 (6.2)
Positive	63 (92.6)	653 (93.8)
p53			0.773
Negative	59 (60.8)	592 (62.3)
Positive	38 (39.2)	358 (37.7)
EGFR overexpression			0.001
Negative	55 (77.5)	558 (90.1)
Positive	16 (22.5)	61 (9.9)
HER2 overexpression			0.084
Negative	33 (84.6)	263 (71.7)
Positive	6 (15.4)	104 (28.3)

MSS: Microsatellite stable; MSI-L: Microsatellite instability-low; MSI-H: Microsatellite instability-high; hMLH1: Human mutL homolog 1; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2.

Table 5 Multivariate analysis of potential risk characteristics for lymph node metastasis

Characteristics	Odds ratio	95%CI	P value
Gender (female)	2.281	1.228-4.235	0.009
Lymphovascular invasion	10.950	5.418-22.134	< 0.0001
Diameter (≥ 20 mm)	3.173	1.324-7.603	0.010
EGFR	2.185	1.020-4.683	0.044

EGFR: Epidermal growth factor receptor.

Table 6 Lymph node metastasis by depth of invasion and histological type n (%)

	Lymph node metastasis
	Presence (n = 104)	Absence (n = 1000)	Total
Well differentiated
Mucosa	0 (0.0)	176 (17.6)	176 (0.0)
Submucosa	4 (3.8)	56 (5.6)	60 (6.7)
Moderate differentiated
Mucosa	3 (0.0)	165 (1.8)	168 (1.8)
Submucosa	42 (40.4)	187 (18.7)	229 (18.3)
Poorly differentiated
Mucosa	11 (10.6)	112 (11.2)	123 (8.9)
Submucosa	25 (24.0)	96 (9.6)	121 (20.7)
Signet ring cell
Mucosa	10 (9.6)	147 (14.7)	157 (6.4)
Submucosa	9 (8.7)	61 (6.1)	70 (12.9)