Clinicopathologic and molecular features associated with patient age in gastric cancer

doi:10.3748/wjg.v21.i22.6905

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Gastroenterol. Jun 14, 2015; 21(22): 6905-6913
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6905

Table 1 Baseline characteristics of the study population n (%)

Characteristic	Age ≤45 yr (n = 202)	Age > 45 yr (n = 1456)	P value
Gender			< 0.001
Male	111 (55.0)	1023 (70.3)
Female	91 (45.0)	433 (29.7)
Reason for medical checkup			< 0.001
Screening	70 (34.7)	724 (49.7)
Symptoms¹	115 (56.9)	613 (42.1)
Bleeding/anemia	13 (6.4)	105 (7.2)
Weight loss	4 (2.0)	14 (1.0)
Comorbidity			< 0.001
No	188 (93.1)	1200 (82.4)
Yes	14 (6.9)	256 (17.6)
Size, cm	4.0 ± 0.3	3.7 ± 0.1	0.083
CEA	1.8 ± 0.2	4.5 ± 1.1	0.631
CA 19-9	38.3 ± 13.0	30.7 ± 6.5	0.090
Synchronous gastric cancer			0.226
No	193 (95.5)	1414 (97.1)
Yes	9 (4.5)	42 (2.9)
Location			< 0.001
Proximal	20 (9.9)	132 (9.1)
Middle	88 (43.6)	433 (29.7)
Distal	59 (29.2)	753 (51.7)
Diffuse	35 (17.3)	138 (9.5)
EGC type	116 (57.4)	889 (61.1)	0.084
I	1 (0.5)	50 (3.4)
II	113 (55.9)	820 (56.3)
III	2 (1.0)	19 (1.3)
AGC type (Borrmann)	86 (42.6)	567 (38.9)	< 0.001
I	0 (0)	22 (1.5)
II	6 (3.0)	118 (8.1)
III	47 (23.3)	334 (22.9)
IV	31 (15.3)	71 (4.9)

¹Symptoms included abdominal discomfort, abdominal pain, soreness, indigestion, anorexia, nausea, or vomiting. AGC: Advanced gastric cancer; CA 19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; EGC: Early gastric cancer.

Table 2 Pathology and stage of gastric cancer n (%)

Variable	Age ≤45 yr(n = 202)	Age > 45 yr (n = 1456)	P value
Pathology (Lauren)			< 0.001
Intestinal	39 (19.3)	870 (59.8)
Diffuse	157 (77.7)	526 (36.1)
Mixed	6 (3.0)	60 (4.1)
Depth of invasion			0.001
T1	117 (57.9)	876 (60.2)
T2	10 (5.0)	143 (9.8)
T3	15 (7.4)	186 (12.8)
T4	33 (16.3)	146 (10.0)
Lymph node metastasis			0.052
N0	122 (60.4)	962 (66.1)
N1	8 (4.0)	127 (8.7)
N2	15 (7.4)	74 (5.1)
N3	25 (12.4)	155 (10.6)
Distant metastasis			< 0.001
M0	153 (75.7)	1267 (87.0)
M1	49 (24.3)	189 (13.0)
Stage			< 0.001
I	122 (60.4)	954 (65.5)
II	10 (5.0)	149 (10.2)
III	21 (10.4)	166 (11.4)
IV	49 (24.3)	187 (12.8)
Lymphatic invasion			0.612
No	121 (59.9)	902 (62.0)
Yes	50 (24.8)	408 (28.0)
Venous invasion			0.024
No	149 (73.8)	1207 (82.9)
Yes	22 (10.9)	102 (7.0)
Perineural invasion			0.043
No	125 (61.9)	1042 (71.6)
Yes	46 (22.8)	264 (18.1)
Baseline adenoma			< 0.001
No	165 (81.7)	1101 (75.6)
Yes	4 (2.0)	195 (13.4)

Table 3 Treatment of gastric cancer n (%)

Variable	Age ≤45 yr(n = 202)	Age > 45 yr (n = 1456)	P value
Endoscopic resection	9 (4.5)	192 (13.2)	0.516
EMR	6 (3.0)	104 (7.1)
ESD	3 (1.5)	88 (6.0)
Operation	172 (85.1)	1160 (79.7)	0.018
Curative resection	157 (77.7)	1108 (76.1)
Palliative resection	15 (7.4)	52 (3.6)
LN dissection			0.017
Not performed	9 (4.5)	24 (1.6)
N1	62 (30.7)	404 (27.7)
N2	95 (47.0)	714 (49.0)
N3	6 (3.0)	18 (1.2)
Radiation			0.101
No	197 (97.5)	1440 (98.9)
Yes	5 (2.5)	16 (1.1)
Chemotherapy			< 0.001
No	132 (65.3)	1194 (82.1)
Yes	70 (34.7)	261 (17.9)

EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; LN: Lymph node.

Table 4 Mortality and recurrence of gastric cancer n (%)

Variable	Age ≤45 yr(n = 202)	Age > 45 yr(n = 1456)
Mean follow-up duration, mo	36.9 ± 25.5	35.2 ± 23.5
Mean time to recurrence, mo¹	17.8 ± 4.1	16.9 ± 1.3
Cured patients	162 (80.2)	1246 (85.6)
Recurrence	17 (10.5)	127 (10.2)
Mortality
Survival	116 (57.4)	838 (57.6)
Death	26 (12.9)	159 (10.9)
Loss to follow-up	60 (29.7)	459 (31.5)
Cause of death
Gastric cancer-related death	21 (10.4)	87 (6.0)
Treatment-related death	2 (1.0)	13 (0.9)
Other causes²	0 (0)	21 (1.4)
Not available	3 (1.5)	38 (2.6)

¹Calculated only for cured patients;

²Other causes of death included malignancy other than gastric cancer, infection not related to treatment of gastric cancer, myocardial infarction, hepatic failure, and trauma.

Table 5 Molecular pathology of gastric cancer n (%)

Variable	Age ≤45 yr(n = 202)	Age > 45 yr(n = 1456)	P value
p53			< 0.001
Negative	123 (60.9)	681 (46.8)
Positive	44 (21.8)	560 (38.5)
MSI			0.006
Stable	85 (42.1)	566 (38.9)
MSI-L	4 (2.0)	43 (3.0)
MSI-H	1 (0.5)	79 (5.4)
HER-2 status			0.006
Negative	78 (38.6)	528 (36.3)
Positive	6 (3.0)	125 (8.6)
EGFR status			0.899
Negative	94 (46.5)	674 (46.3)
Positive	12 (5.9)	99 (6.8)

EGFR: Epidermal growth factor receptor; HER-2: Human epidermal growth factor receptor-2; MSI: Microsatellite instability; MSI-H: MSI-high; MSI-L: MSI-low.

Table 6 Helicobacter pylori and associated changes of gastric cancer

Variable	Age ≤45 yr(n = 202)	Age > 45 yr(n = 1456)	P value
Helicobacter pylori grade	0.8 ± 1.0	0.6 ± 0.9	0.012
Neutrophil infiltration	1.4 ± 0.9	1.4 ± 0.9	0.866
Mononuclear cell infiltration	1.9 ± 0.5	1.9 ± 0.5	0.679
Atrophic gastritis	0.5 ± 0.7	1.0 ± 0.9	< 0.001
Intestinal metaplasia	0.5 ± 0.7	1.0 ± 0.8	< 0.001

Scored according to the Updated Sydney System: 0 (absent), 1 (mild), 2 (moderate), and 3 (marked).

Table 7 Univariate and multivariate analyses of predictors for mortality

Parameter	Univariate analysis		Multivariate analysis
Parameter	HR (95%CI)	P value	HR (95%CI)	P value
Age ( ≤ 45/> 45 yr)	1.10 (0.72-1.66)	0.664
Gender (male/female)	0.87 (0.63-1.19)	0.384
Curative resection (no/yes)	6.38 (4.33-9.40)	< 0.001
CEA	1.00 (1.00-1.00)	< 0.001
CA19-9	1.00 (1.00-1.00)	< 0.001
Size, cm	1.24 (1.20-1.28)	< 0.001
Pathology
Intestinal	1.00 (reference)
Diffuse	2.77 (2.03-3.78)	< 0.001
Mixed	1.95 (0.89-4.26)	0.095
T stage (III, IV vs I, II)	26.07 (16.42-41.40)	< 0.001
N stage (N+ vs N-)	21.29 (12.81-35.36)	< 0.001
M stage (M+ vs M-)	42.17 (30.75-57.84)	< 0.001	6.70 (1.58-24.49)	0.010
Stage (III, IV vs I, II)	46.39 (30.75-69.98)	< 0.001	10.78 (2.69-43.22)	0.001
Lymphatic invasion (yes/no)	11.84 (7.45-18.83)	< 0.001
Venous invasion (yes/no)	14.75 (9.95-21.87)	< 0.001
Perineural invasion (yes/no)	14.34 (9.42-251.85)	< 0.001
Atrophic gastritis	1.06 (0.77-1.45)	0.736
Intestinal metaplasia	1.00 (0.76-1.30)	0.977
p53 (positive/negative)	1.45 (0.99-2.12)	0.058
MSI (MSI-L vs stable)	1.30 (0.53-3.21)	0.565
MSI (MSI-H vs stable)	0.82 (0.53-1.76)	0.602
HER-2 (positive/negative)	0.57 (0.26-1.25)	0.158
EGFR (positive/negative)	0.66 (0.27-1.65)	0.377

CA 19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; EGFR: Epidermal growth factor receptor; HER-2: Human epidermal growth factor receptor-2; MSI: Microsatellite instability; MSI-H: MSI-high; MSI-L: MSI-low.

Citation: Seo JY, Jin EH, Jo HJ, Yoon H, Shin CM, Park YS, Kim N, Jung HC, Lee DH. Clinicopathologic and molecular features associated with patient age in gastric cancer. World J Gastroenterol 2015; 21(22): 6905-6913
URL: https://www.wjgnet.com/1007-9327/full/v21/i22/6905.htm
DOI: https://dx.doi.org/10.3748/wjg.v21.i22.6905