IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

Table 3 Clinical and molecular features of sessile serrated adenomas with cytological dysplasia, traditional serrated adenomas, non-serrated adenomas (tubular or tubulovillous adenoma), and colorectal carcinomas according to disease stage n (%)

Clinical or molecular feature	Histological type									P value
	SSA with cytological dysplasia	Colorectal adenoma				Colorectal carcinoma
		TSA without HGD	TSA with HGD	Non-serrated adenoma without HGD	Non-serrated adenoma with HGD	Stage I	Stage II	Stage III	Stage IV
All cases	10	91	15	80	105	171	217	292	114
Sex
Male	5 (50)	55 (60)	9 (60)	53 (66)	54 (51)	107 (63)	123 (57)	168 (58)	73 (64)	0.50
Female	5 (50)	36 (40)	6 (40)	27 (34)	51 (49)	64 (37)	94 (43)	124 (42)	41 (36)
Age (mean ± SD)	74.1 ± 4.7	60.9 ± 12.3	62.7 ± 13.6	66.6 ± 11.2	66.3 ± 10.5	65.1 ± 11.0	67.4 ± 11.5	66.6 ± 12.5	63.4 ± 9.5	0.0016
Tumor size (mm)	12.3 ± 6.4	9.7 ± 4.7	12.8 ± 4.3	11.0 ± 7.4	29.3 ± 17.3	26.3 ± 15.8	53.1 ± 23.5	50.5 ± 22.7	50.9 ± 19.6	< 0.0001
(mean ± SD)
Tumor location
Rectum	0 (0)	16 (18)	5 (33)	11 (14)	23 (22)	65 (38)	73 (34)	135 (46)	37 (33)	< 0.0001
Distal colon	1 (10)	39 (44)	7 (47)	26 (34)	27 (26)	44 (25)	64 (29)	59 (20)	42 (37)
Proximal colon	9 (90)	34 (38)	3 (20)	39 (51)	54 (52)	62 (36)	80 (37)	98 (34)	34 (30)
BRAF mutation
Wild-type	2 (20)	28 (31)	7 (47)	78 (98)	102 (98)	161 (95)	204 (94)	282 (97)	103 (95)	< 0.0001
Mutant	8 (80)	61 (69)	8 (53)	2 (2.5)	2 (1.9)	9 (5.3)	13 (6.0)	9 (3.0)	6 (5.5)
KRAS mutation
Wild-type	10 (100)	74 (83)	11 (73)	64 (80)	48 (46)	108 (64)	145 (69)	202 (70)	84 (74)	< 0.0001
Mutant	0 (0)	15 (17)	4 (27)	16 (20)	57 (54)	62 (36)	66 (31)	88 (30)	29 (26)
PIK3CA mutation
Wild-type	10 (100)	89 (100)	14 (93)	77 (99)	99 (94)	161 (94)	194 (89)	249 (85)	103 (90)	< 0.0001
Mutant	0 (0)	0 (0)	1 (6.7)	1 (1.3)	6 (5.7)	10 (5.9)	23 (11)	43 (15)	11 (9.7)
MSI status
MSS/MSI-low	6 (60)	90 (99)	15 (100)	80 (100)	105 (100)	163 (95)	198 (91)	276 (95)	110 (96)	< 0.0001
MSI-high	4 (40)	1 (1.1)	0 (0)	0 (0)	0 (0)	8 (4.7)	19 (8.8)	16 (5.5)	4 (3.5)
IGF2 DMR0	69.0 ± 10.8	61.6 ± 19.6	50.2 ± 18.7	59.0 ± 15.8	52.0 ± 13.6	55.7 ± 15.8	53.4 ± 13.3	55.5 ± 12.9	53.1 ± 12.9	< 0.0001
methylation level (mean ± SD)
LINE-1	58.3 ± 8.4	58.8 ± 4.7	55.7 ± 5.4	59.5 ± 5.9	56.9 ± 5.5	55.8 ± 7.2	53.1 ± 6.2	55.1 ± 6.5	54.1 ± 7.6	< 0.0001
methylation level (mean ± SD)

Percentage indicates the proportion of patients of each histological type who met the criteria for a specific clinical or molecular feature. P values were calculated by analysis of variance for age, tumor size, methylation levels of IGF2 DMR0 and LINE-1 and by χ² or Fisher’s exact test for all other variables. The P value for significance was adjusted by Bonferroni correction to 0.0050 (= 0.05/10). HGD: High-grade dysplasia; HP: Hyperplastic polyp; MSI: Microsatellite instability; MSS: Microsatellite stable; SSA: Sessile serrated adenoma; TSA: Traditional serrated adenoma; IGF2: Insulin-like growth factor 2.