Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway

Table 1 Clinicopathologic and histologic features of Annexin A10 expression in colorectal cancers n (%)

Parameter	Annexin A10no-expression(n = 1067, 94.2%)	Annexin A10expression(n = 66, 5.8%)	P value
Age (mean ± SD)	61.0 ± 11.1	58.1 ± 12.6	0.0381
Sex			< 0.001
Male	650 (60.9)	27 (40.9)
Female	417 (39.1)	39 (59.1)
Location			< 0.001
Proximal colon	237 (22.2)	42 (63.6)
Distal colon	430 (40.3)	11 (16.7)
Rectum	400 (37.5)	13 (19.7)
Gross type			0.027
Fungating	708 (66.3)	35 (53.0)
Ulcerative	359 (33.7)	31 (47.0)
T category			< 0.0012
1	47 (4.4)	1 (1.5)
2	164 (15.4)	0 (0.0)
3	756 (70.8)	52 (78.8)
4	100 (9.4)	13 (19.7)
N category			< 0.0012
0	558 (52.3)	16 (24.2)
1	290 (27.2)	23 (34.9)
2	219 (20.5)	27 (40.9)
M category			0.049
0	892 (83.6)	49 (74.2)
1	175 (16.4)	17 (25.8)
Stage			< 0.0012
I	173 (16.2)	0 (0.0)
II	351 (32.9)	15 (22.7)
III	368 (34.5)	34 (51.5)
IV	175 (16.4)	17 (25.7)
Differentiation			0.002
Well Differentiated	64 (6.0)	2 (3.0)
Moderately Differentiated	970 (90.9)	56 (84.9)
Poorly Differentiated	33 (3.1)	8 (12.1)
Luminal necrosis			< 0.001
Absent	83 (7.8)	18 (27.3)
Present	984 (92.2)	48 (72.7)
Tumor budding			0.2643
Absent	36 (3.4)	0 (0.0)
Present	1031 (96.6)	66 (100.0)
Tumor-infiltrating Lymphocytes			0.316
Low TILs (< 8/HPF)	802 (75.2)	39 (59.1)
High TILs (≥ 8/HPF)	265 (24.8)	27 (40.9)
Crohn’s-like Lymphoid reaction			0.470
Absent	908 (85.1)	54 (81.8)
Present	159 (14.9)	12 (18.2)
Luminal serration			< 0.0013
Absent	1039 (97.4)	50 (75.8)
Present	28 (2.6)	16 (24.2)
Mucin production
Absent	958 (89.8)	43 (65.1)	< 0.001
Present	109 (10.2)	23 (34.9)

1Student’s t-test;

²Wilcoxon rank-sum test;

³Fisher’s exact test. S.D: Standard deviation; HPF: High power field.

Table 2 Comparison of Annexin A10 expression with other molecular characteristics in colorectal cancers n (%)

Parameter	Annexin A10	Annexin A10	P value
	no-expression	expression
	(n = 1067, 94.2%)	(n = 66, 5.8%)
CIMP			< 0.0011
CIMP-N	1029 (96.4)	41 (62.1)
CIMP-P	38 (3.6)	25 (37.9)
MSI			< 0.0011
MSS	995 (93.2)	49 (74.2)
MSI	72 (6.8)	17 (25.8)
KRAS mutation			0.399
(n = 1071)
Wild type	745 (73.8)	42 (68.8)
Mutant type	265 (26.2)	19 (31.2)
BRAF mutation			< 0.0011
(n = 1005)
Wild type	912 (96.4)	50 (84.7)
Mutant type	34 (3.6)	9 (15.3)

¹Fisher’s exact test. CIMP: CpG island methylator phenotype; MSI: Microsatellite instability.

Table 3 Univariate and multivariate Cox proportional hazards models for overall survival of stage IV colorectal cancers

	Univariate analysis		Multivariate analysis
Variable	HR (95%CI)	P value	HR (95%CI)	P value
Differentiation (undifferentiated/differentiated)	2.20 (1.31-3.72)	0.003	1.95 (1.07-3.56)	0.030
Tumor location (proximal colon/distal colon, rectum)	1.66 (1.16-2.38)	0.005	1.60 (1.06-2.42)	0.025
Adjuvant chemotherapy (treatment/no-treatment)	0.42 (0.27-0.66)	< 0.001	0.47 (0.27-0.81)	0.006
Annexin A10 (expression/no-expression)	3.13 (1.83-5.38)	< 0.001	2.38 (1.18-4.83)	0.016
Age (yr) (≥ 65/< 65)	1.54 (1.10-2.15)	0.012	1.37 (0.92-2.03)	0.123
Gross pattern (ulcerative/fungating)	1.41 (1.01-1.96)	0.042	1.18 (0.81-1.71)	0.387
CIMP (CIMP-P/CIMP-N)	2.24 (1.24-4.06)	0.008	1.13 (0.44-2.89)	0.801
MSI (MSI/MSS)	2.46 (1.08-5.63)	0.033	1.46 (0.44-4.86)	0.540
BRAF mutation (Mt/Wt)	2.42 (1.12-5.19)	0.024	1.67 (0.71-3.91)	0.239
Sex (male/female)	1.03 (0.74-1.45)	0.858	-	-
KRAS mutation (Mt/Wt)	1.09 (0.75-1.58)	0.653	-	-

HR: Hazard ratio; CI: Confidence interval; CIMP-P: CpG island methylator phenotype-positive; CIMP-N: CpG island methylator phenotype-negative; MSI: Microsatellite instability; MSS: Microsatellite stable; Mt: Mutant type; Wt: Wild type.