ARID1A expression in gastric adenocarcinoma: Clinicopathological significance and correlation with DNA mismatch repair status

Table 1 Immunohistochemical expression of mismatch repair proteins

Immunohistochemical expression	n = 489
Loss of MLH1 and PMS2	33
Loss of PMS2	3
Loss of MSH2 and MSH6	1
Loss of all four proteins	1
Retention of all four proteins	451

Table 2 Clinicopathologic features of the 489 patients with gastric cancers according to mismatch repair status n (%)

	Total(n = 489)	MMR		P value
		Deficient (n = 38)	Intact(n = 451)
Age (yr)				< 0.0011
mean ± SD	61.0 ± 11.8	68.6 ± 9.2	60.4 ± 11.7
Gender				0.0042
Male	327 (66.9)	17 (44.7)	310 (68.7)
Female	162 (33.1)	21 (55.3)	141 (31.3)
Serum CEA (ng/mL)				0.9101
mean ± SD	36.3 ± 315.7	4.4 ± 6.0	39.0 ± 328.7
Tumor size (mm)				0.8311
mean ± SD	80.3 ± 45.1	79.0 ± 38.9	80.4 ± 45.6
Tumor location				0.0212
Fundus and Corpus	356 (72.8)	21 (55.3)	335 (74.3)
Antrum	133 (27.2)	17 (44.7)	116 (25.7)
Histology				0.0232
Differentiated type	193 (39.5)	22 (57.9)	171 (37.9)
Undifferentiated type	296 (60.5)	16 (42.1)	280 (62.1)
Lymphatic invasion				1.0002
Absent	137 (28.0)	10 (26.3)	127 (28.2)
Present	352 (72.0)	28 (73.7)	324 (71.8)
Venous invasion				0.6092
Absent	281 (57.5)	20 (52.6)	261 (57.9)
Present	208 (42.5)	18 (47.4)	190 (42.1)
Primary tumor				0.6122
T2, 3	241 (49.3)	22 (57.9)	219 (48.6)
T4	248 (50.7)	16 (42.1)	232 (51.4)
Lymph node involvement				0.4382
N0	118 (24.1)	11 (28.9)	107 (23.7)
N1, 2, 3	371 (75.9)	27 (71.1)	344 (76.3)
Distant metastasis				0.2022
M0	336 (68.7)	30 (78.9)	306 (67.8)
M1	153 (31.3)	8 (21.1)	145 (32.2)
Stage				0.8602
Stage I, II	172 (35.2)	14 (36.8)	158 (35.0)
Stage III, IV	317 (64.8)	24 (63.2)	293 (65.0)
Residual disease				0.1612
Negative	375 (76.7)	33 (86.8)	342 (75.8)
Positive	114 (23.3)	5 (13.2)	109 (24.2)

¹Mann-Whitney U test;

²Fisher’s exact test. MMR: Mismatch repair; CEA: Carcinoembryonic antigen.

Table 3 Clinicopathological features of 489 patients with gastric cancer according to ARID1A expression n (%)

	ARID1A expression		P value
	Loss/weak(n = 109)	Retained(n = 380)
Age (yr)			0.2121
mean ± SD	62.1 ± 10.9	60.7 ± 12.0
Gender			0.4192
Male	69 (63.3)	258 (67.9)
Female	40 (36.7)	122 (32.1)
Serum CEA (ng/mL)			0.9371
mean ± SD	39.7 ± 363.4	35.3 ± 301.3
Tumor size (mm)			0.3361
mean ± SD	83.9 ± 46.1	79.2 ± 44.8
Tumor location			0.0672
Fundus and Corpus	87 (79.8)	269 (70.8)
Antrum	22 (20.2)	111 (29.2)
Histology			0.7392
Differentiated type	41 (37.6)	152 (40.0)
Undifferentiated type	68 (62.4)	228 (60.0)
Lymphatic invasion			0.0222
Absent	21 (19.3)	116 (30.5)
Present	88 (80.7)	264 (69.5)
Venous invasion			0.4432
Absent	59 (54.1)	222 (58.4)
Present	50 (45.9)	158 (41.6)
Primary tumor			0.0652
T2, 3	45 (41.3)	184 (48.4)
T4	64 (58.7)	196 (51.6)
Lymph node involvement			0.0422
N0	18 (16.5)	100 (26.3)
N1, 2, 3	91 (83.5)	280 (73.7)
Distant metastasis			0.7252
M0	73 (67.0)	263 (69.2)
M1	36 (33.0)	117 (30.8)
Stage			0.1112
Stage I, II	31 (28.4)	141 (37.1)
Stage III, IV	78 (71.6)	239 (62.9)
Residual disease			0.7982
Negative	85 (78.0)	290 (76.3)
Positive	24 (22.0)	90 (23.7)

¹Mann-Whitney U test;

²Fisher’s exact test. CEA: Carcinoembryonic antigen.

Table 4 Cox’s proportional hazard model analysis of prognostic factors in 489 patients with gastric cancers

Variables	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age (yr)
≥ 60/ ≤ 59	1.22	0.94-1.59	0.123
Sex
Male/female	0.72	0.56-0.94	0.015	0.72	0.55-0.95	0.020
Serum CEA (ng/mL)
≥ 5.0/< 5.0	1.75	1.33-2.33	< 0.001	1.54	1.15-2.06	0.004
Tumor size (mm)
≥ 50/< 50	3.70	2.50-5.26	< 0.001	1.88	1.25-2.83	0.002
Histology
Undifferentiated/differentiated type	1.54	1.12-2.01	0.002	1.64	1.24-2.16	0.001
Lymphatic invasion
Present/absent	3.23	2.22-4.55	< 0.001	1.48	0.98-2.22	0.062
Venous invasion
Present/absent	1.89	1.45-2.44	< 0.001	1.21	0.92-1.60	0.171
Stage
Stage III, IV/I, II	9.09	5.56-14.29	< 0.001	3.77	2.30-6.17	0.023
Residual disease
Positive/negative	6.25	5.00-8.33	< 0.001	3.79	2.85-5.03	< 0.001
MMR status
Deficient/intact	0.74	0.44-1.25	0.264
ARID1A status
Abnormal/retained	1.30	0.98-1.75	0.070	1.36	1.01-1.84	0.040

HR: Hazards ratio; CEA: Carcinoembryonic antigen; MMR: Mismatch repair.

Table 5 Relationship between mismatch repair protein and ARID1A expression n (%)

	ARID1A expression
	Loss		Weak
	Homo (n = 43)	Hetero (n = 29)	Homo (n = 21)	Hetero (n = 16)	Retained (n = 380)	P value
MMR status						< 0.0011
Deficient	10 (26.3)	4 (10.5)	2 (5.3)	2 (5.3)	20 (52.6)
(n = 38)
Intact	33 (7.3)	25 (5.6)	19 (4.2)	14 (3.1)	360 (79.8)
(n = 451)

¹Extended Fisher’s exact test. MMR: Mismatch repair; Homo: Homogeneous; Hetero: Heterogeneous.