Liver metastasis is the only independent prognostic factor in AFP-producing gastric cancer

Table 1 Association between clinicopathological characteristics and α-fetoprotein expression n (%)

Characteristic	n	Gastric cancer		P value1
		AFP-producing	AFP-non producing
Total	1299	23	1276
Sex				0.9974
Male	875	16 (70)	859 (67)
Female	424	7 (30)	417 (33)
Age (yr)				0.5835
Mean	64.5 (range: 27-94)
< 65	610	9 (39)	601 (47)
≥ 65	689	14 (61)	675 (53)
Location				0.8753
Upper	292	4 (17)	288 (23)
Middle	591	10 (44)	581 (45)
Lower	416	9 (39)	407 (32)
Macroscopic type				< 0.0001
Type 0-I/II/III	690	2 (9)	688 (54)
Type 1/2/3/4	609	21 (91)	588 (46)
Histopathological grading				0.8155
Differentiated	596	10 (43)	586 (46)
Undifferentiated	703	13 (57)	690 (54)
Tumor size (mm)				0.0073
< 40	614	4 (17)	610 (48)
≥ 40	685	19 (83)	666 (52)
Venous invasion				< 0.0001
Negative	937	5 (22)	932 (73)
Positive	362	18 (78)	344 (27)
Lymphatic invasion				0.0071
Negative	726	6 (26)	720 (56)
Positive	573	17 (74)	556 (44)
TNM classification
pT categories				0.036
T1	664	4 (17)	660 (52)
T2	122	3 (13)	119 (9)
T3	217	7 (31)	210 (16)
T4	296	9 (39)	287 (23)
pN categories				0.0007
N0	821	9 (39)	812 (63)
N1	140	9 (39)	131 (10)
N2	137	3 (13)	134 (11)
N3	201	2 (9)	199 (16)
pStage
I	769	3 (13)	766 (60)	0.0002
II	137	3 (13)	134 (11)
III	195	9 (39)	186 (14)
IV	198	8 (35)	190 (15)
Absent	955	12 (52)	943 (74)	0.0192
Present	344	11 (48)	333 (26)
Liver metastasis				< 0.0001
Absent	1245	13 (57)	1232 (97)
Present	54	10 (43)	44 (3)

Significantly different values are highlighted using boldface type.

¹P values are from χ² or Fisher’s exact test and were significant at < 0.05. AFP: α-fetoprotein; TNM: Tumor, nodes, metastasis.

Table 2 Univariate and multivariate survival analyses in 1299 gastric cancer patients

Factor	Univariate1	Multivariate2
	P value	HR	95%CI	P value
Sex
Male vs female	0.3121
Age (yr)
65 ≤vs < 65	0.0033
Location
U vs ML	0.0027
Macroscopic type
Type 1/2/3/4 vs Type 0-I/II/III	< 0.0001	3.760	2.012-7.013	< 0.0001
Tumor size (mm)
40 ≤vs < 40	< 0.0001	2.128	1.259-3.597	0.0048
Histological type
Undifferentiated vs Differentiated	0.014
pT categories
T2/3/4 vs T1	< 0.0001
Venous invasion
Positive vs Negative	< 0.0001	1.721	1.247-2.375	0.0010
Lymphatic invasion
Positive vs Negative	< 0.0001	2.793	1.656-4.717	0.0001
pN categories
Positive vs Negative	< 0.0001	2.513	1.614-3.951	< 0.0001
AFP
producing vs non producing	0.0018
Liver metastasis
Positive vs Negative	< 0.0001	3.152	2.116-4.558	< 0.0001

¹The Kaplan-Meier method, and significance was determined by the log-rank test;

²Multivariate survival analysis was performed using Cox’s proportional hazard model. AFP: α-fetoprotein.

Table 3 Comparison of recurrence patterns between patients with and without α-fetoprotein -producing gastric cancer n (%)

Site	GC patients with recurrence
	AFP-producing GC (n = 11)	AFP-non producing GC (n = 256)
Peritoneum	1 (9.1)	113 (44.1)
Liver	10 (90.9)	44 (17.2)
Lung	1 (9.1)	3 (1.2)
Bone	0 (0.0)	13 (5.1)
Lymph nodes	0 (0.0)	48 (18.8)
Others	0 (0.0)	46 (18.0)

The incidence of recurrence was 47.8% in the α-fetoprotein (AFP)-producing group and 20.0% in the AFP-non producing group. The most likely recurrence pattern was liver metastasis and peritoneal metastasis in the AFP-producing group and AFP-non producing group, respectively. GC: Gastric cancer.

Table 4 Univariate and multivariate survival analyses in α-fetoprotein-producing gastric cancer patients

Factor	Univariate1	Multivariate2
	P value	HR	95%CI	P value
Sex
Male vs female	0.3574
Age (yr)
65 ≤vs < 65	0.0917
Location
U vs ML	0.4311
Macroscopic type
Type 1/2/3/4 vs Type 0-I/II/III	0.3422
Tumor size (mm)
40 ≤vs < 40	0.3539
Histological type
Undifferentiated vs Differentiated	0.0503
pT categories
T2/3/4 vs T1	0.1428
Venous invasion
Positive vs negative	0.6696
Lymphatic invasion
Positive vs negative	0.6188
pN categories
Positive vs negative	0.9855
Liver metastasis
Positive vs negative	0.0006	17.587	2.112-147.12	0.0081

¹The Kaplan-Meier method, and significance was determined by the log-rank test;

²Multivariate survival analysis was performed using Cox’s proportional hazard model.

Table 5 Comparison of clinicopathological factors between α-fetoprotein-producing gastric cancer patients with and without liver metastasis n (%)

Factor	n	Liver metastasis		P value1
		Absence	Presence
Total	23	13	10
Sex				0.1203
Male	14	10 (77)	4 (40)
Female	19	13 (23)	6 (60)
Age (yr)				0.4173
< 65	9	4 (31)	5 (50)
≥ 65	14	9 (69)	5 (50)
Location				0.1717
Upper	4	0 (0)	4 (40)
Middle	10	7 (54)	3 (30)
Lower	9	6 (46)	3 (30)
Macroscopic type				0.4862
Type 0-I/II/III	2	2 (15)	0 (0)
Type 1/2/3/4	21	11 (85)	10 (100)
Histopathological grading				0.2215
Differentiated	10	4 (31)	6 (60)
Undifferentiated	13	9 (69)	4 (40)
Tumor size (mm)				0.6036
< 40	4	3 (23)	1 (10)
≥ 40	19	10 (77)	9 (90)
Venous invasion				1.0000
Negative	5	3 (23)	2 (20)
Positive	18	10 (77)	8 (80)
Lymphatic invasion				0.0886
Negative	7	6 (46)	1 (10)
Positive	16	7 (54)	9 (90)
TNM classification
pT categories				0.7007
T1	4	3 (23)	1 (10)
T2	3	2 (15)	1 (10)
T3	7	5 (39)	2 (20)
T4	9	3 (23)	6 (60)
pN categories				0.9049
N0	9	5 (39)	4 (40)
N1	9	4 (31)	5 (50)
N2	3	2 (15)	1 (10)
N3	2	2 (15)	0 (0)
pStage				0.6736
I	3	3 (23)	0 (0)
II	3	2 (15)	1 (10)
III	9	5 (39)	4 (40)
IV	8	3 (23)	5 (50)

Significantly different values are highlighted using boldface type.

¹P values are from χ² or Fisher’s exact test and were significant at < 0.05. No significantly different prognostic factor was observed between patients with or without liver metastasis in α-fetoprotein-producing gastric cancer. TNM: Tumor, nodes, metastasis.