Differential mucin phenotypes and their significance in a variation of colorectal carcinoma

Table 1 Clinicopathologic characteristics in colorectal carcinoma n (%)

Variables		WMDA	PDA	MUA	SRCC
		(n = 63)	(n = 91)	(n = 81)	(n = 15)
Gender	Male	39 (61.9)	45 (49.5)	46 (56.8)	6 (40.0)
	Female	24 (38.1)	46 (50.5)	35 (43.2)	9 (60.0)
Age (yr)	Range	32-87	35-92	26-90	30-82
	Median	65	64	71	70
Family history of CRC	Yes	5 (7.9)	5 (6.1)	5 (6.3)	2 (13.3)
	No	58 (92.1)	77 (93.9)	75 (93.7)	13 (86.7)
	Unknown		9	1
Location	Left-sided	43 (68.3)	38 (41.8)	40 (49.4)	6 (40.0)
	Right-sided	20 (31.7)	53 (58.2)	41 (50.6)	9 (60.0)
Depth	Up tp MP	10 (15.9)	4 (4.4)	5 (6.2)	1 (6.7)
	Beyond MP	53 (84.1)	87 (95.6)	76 (93.8)	14 (93.3)
Venous invasion	Yes	48 (76.2)	77 (85.6)	41 (50.6)	14 (93.3)
	No	15 (23.8)	13 (14.4)	40 (49.4)	1 (6.7)
	Unknown		1
Lymphatic invasion	Yes	35 (55.6)	82 (91.1)	54 (66.7)	12 (80.0)
	No	28 (44.4)	8 (8.9)	27 (33.3)	3 (20.0)
	Unknown		1
Nodal metastasis	Yes	34 (54.0)	69 (78.4)	37 (46.8)	9 (64.3)
	No	29 (46.0)	19 (21.6)	42 (53.2)	5 (35.7)
	Unknown		3	2	1
Chemotherapy	Yes	17 (27.0)	42 (53.8)	31 (41.9)	7 (46.7)
	No	46 (73.0)	36 (46.2)	43 (58.1)	8 (53.3)
	Unknown		13	7
Irradiation	Yes	4 (6.3)	2 (2.6)	3 (4.1)	1 (7.1)
	No	59 (93.7)	76 (97.4)	71 (95.9)	14 (92.9)
	Unknown		13	7
TNM stage	I/II	29 (46.0)	17 (18.9)	40 (50.0)	4 (26.7)
	III/IV	34 (54.0)	73 (81.1)	40 (50.0)	11 (73.3)
	Unknown		1	1	0

CRC: Colorectal carcinoma; WMDA: Well-to-moderately differentiated adenocarcinoma; PDA: Poorly differentiated adenocarcinoma; MUA: Mucinous adenocarcinoma; SRCC: Signet-ring cell carcinoma; MP: Muscularis propria; TNM: Tumor node metastasis.

Table 2 Expression levels of the mucin core proteins in the adenoma carcinoma sequence

	Histology		MUC2			MUC5AC
No. of patient	Adenoma	Carcinoma	Adenoma	Carcinoma	P value1	Adenoma	Carcinoma	P value1
208	TV	WMDA	4	3	ND	4	1	ND
225	T	WMDA	4	4		3	2
237	TV	WMDA	4	4		2	4
243	TV	WMDA	4	4		4	4
84	TV	PDA	4	2	0.016	4	0	0.042
86	TV	PDA	4	0		1	0
87	TV	PDA	4	0		0	0
102	TV	PDA	4	0		4	0
116	T	PDA	2	0		2	0
138	T	PDA	4	0		3	0
148	T	PDA	3	0		0	0
15	TV	MUA	4	4	0.063	3	0	0.016
36	TV	MUA	4	4		3	3
37	TV	MUA	4	4		0	0
51	TV	MUA	4	4		3	3
131	T	MUA	4	2		3	1
148	TV	MUA	4	2		4	0
151	TV	MUA	4	3		3	1
155	TV	MUA	4	4		4	2
175	TV	MUA	4	4		4	2
191	TV	MUA	4	3		3	0

¹Wilcoxon signed-rank test. MUC: Mucin; T: Tubular adenoma; TV: Tubulovillous adenoma; WMDA: Well-to-moderately differentiated adenocarcinoma; PDA: Poorly differentiated adenocarcinoma; MUA: Mucinous adenocarcinoma; ND: Not determined.

Table 3 Expression of the mucin core proteins and clinicopathologic variables n (%)

		WMDA			PDA			MUA
		MUC2			MUC2			MUC2
		-	+	P value	-	+	P value	-	+	P value
Median age (range), yr		64 (32-82)	64 (34-87)	0.783	64 (35-92)	66.5 (55-86)	0.633	65 (52-88)	71 (26-90)	0.842
Gender	Male	21 (33.3)	18 (28.6)	0.537	41 (45.1)	4 (4.4)	1.000	1 (1.2)	45 (55.6)	0.311
	Female	11 (17.5)	13 (20.6)		42 (46.1)	4 (4.4)		3 (3.7)	32 (39.5)
Locus	Right-sided	10 (15.9)	10 (15.9)	0.932	47 (51.6)	6 (6.6)	0.461	1 (1.2)	40 (49.4)	0.359
	Left-sided	22 (34.9)	21 (33.3)		36 (39.6)	2 (2.2)		3 (3.7)	37 (45.7)
Venous invasion	Yes	24 (38.1)	24 (38.1)	1.000	71 (79.0)	6 (6.6)	0.325	3 (3.7)	38 (46.9)	0.616
	No	8 (12.7)	7 (11.1)		11 (12.2)	2 (2.2)		1 (1.2)	39 (48.1)
Lymphatic invasion	Yes	21 (33.3)	14 (22.2)	0.102	76 (84.4)	6 (6.7)	0.148	1 (1.2)	51 (63.0)	1.000
	No	11 (17.5)	17 (27.0)		6 (6.7)	2 (2.2)		3 (3.7)	26 (32.1)
Nodal metastasis	Yes	20 (31.7)	14 (22.2)	0.167	64 (72.7)	5 (5.7)	0.362	2 (2.5)	35 (44.3)	1.000
	No	12 (19.0)	17 (27.0)		16 (18.2)	3 (3.4)		2 (2.5)	40 (50.6)
TNM stage	I/II	12 (19.0)	17 (27.0)	0.167	14 (15.6)	3 (3.3)	0.171	2 (2.5)	38 (48.1)	1.000
	III/IV	20 (31.7)	14 (22.2)		68 (75.5)	5 (5.6)		2 (2.5)	37 (46.8)
dMMR	Yes	ND			16 (17.6)	3 (3.3)	0.356	ND
	No				67 (73.6)	5 (5.5)
		MUC5AC			MUC5AC			MUC5AC
		-	+	P value	-	+	P value	-	+	P value
Median age (range), yr		64 (32-83)	69 (47-87)	0.099	63 (36-87)	70 (35-92)	0.096	67 (34-87)	72 (26-90)	0.061
Gender	Male	26 (41.3)	13 (20.6)	0.677	22 (24.2)	23 (25.3)	0.919	23 (28.4)	23 (28.4)	0.371
	Female	18 (28.6)	6 (9.5)		22 (24.2)	24 (26.3)		14 (17.3)	21 (25.9)
Locus	Right-sided	10 (15.9)	10 (15.9)	0.410	20 (22.0)	33 (36.3)	0.017	12 (14.8)	29 (35.8)	0.003
	Left-sided	34 (54.0)	9 (14.3)		24 (26.4)	14 (15.4)		25 (30.9)	15 (18.5)
Venous invasion	Yes	34 (54.0)	14 (22.2)	0.757	38 (42.2)	39 (43.3)	1.000	16 (19.8)	25 (30.9)	0.224
	No	10 (15.9)	5 (7.9)		6 (6.7)	7 (7.8)		21 (25.9)	19 (23.5)
Lymphatic invasion	Yes	26 (41.3)	9 (14.3)	0.560	41 (45.6)	41 (45.6)	0.714	25 (30.9)	29 (35.8)	0.875
	No	18 (28.6)	10 (15.9)		3 (3.3)	5 (5.6)		12 (14.8)	15 (18.5)
Nodal metastasis	Yes	23 (36.5)	11 (17.5)	0.892	40 (45.5)	29 (33.0)	0.010	17 (21.5)	20 (25.3)	0.950
	No	21 (33.3)	8 (12.7)		4 (4.5)	15 (17.0)		19 (24.1)	23 (29.1)
TNM stage	I/II	21 (33.3)	8 (12.7)	0.892	3 (3.3)	14 (15.6)	0.010	18 (22.8)	22 (27.8)	0.918
	III/IV	23 (36.5)	11 (17.5)		41 (45.6)	32 (35.6)		18 (22.8)	21 (26.6)
dMMR	Yes	ND			3 (3.3)	16 (17.6)	0.003	ND
	No				41 (45.1)	31 (34.1)

MUC: Mucin; WMDA: Well-to-moderately differentiated adenocarcinoma; PDA: Poorly differentiated adenocarcinoma; MUA: Mucinous adenocarcinoma; dMMR: Mismatch-repair deficiency; ND: Not determined; TNM: Tumor node metastasis.

Table 4 Prognostic significance of clinicopathologic variables in well-to-moderately differentiated adenocarcinoma and poorly differentiated adenocarcinoma

	Recurrence/metastasis				Death
	Parameter		HR (95%CI)	P value	Parameter		HR (95%CI)	P value
WMDA	Univariate analysis				Univariate analysis
		Age (over 65 yr)	2.215 (0.974-5.037)	0.058		Age (over 65 yr)	1.984 (0.794-4.955)	0.142
		Gender (male)	0.887 (0.398-1.975)	0.769		Gender (male)	2.194 (0.727-6.617)	0.163
		Location (right-sided)	1.268 (0.559-2.875)	0.570		Location (right-sided)	1.335 (0.524-3.402)	0.545
		TNM stage (III/IV)	3.642 (1.446-9.170)	0.006		TNM stage (III/IV)	2.632 (0.990-6.996)	0.052
		MUC2 positive	0.477 (0.210-1.082)	0.077		MUC2 positive	0.527 (0.207-1.341)	0.179
		MUC5AC positive	1.389 (0.613-3.145)	0.431		MUC5AC positive	1.803 (0.723-4.497)	0.206
	Multivariate analysis				Multivariate analysis
		Age (over 65 yr)	2.220 (0.965-5.017)	0.061
		TNM stage (III/IV)	3.473 (1.370-8.805)	0.009
		MUC2 positive	0.554 (0.243-1.265)	0.161
PDA	Univariate analysis				Univariate analysis
		Age (over 65 yr)	0.891 (0.495-1.602)	0.700		Age (over 65 yr)	0.985 (0.955-1.016)	0.331
		Gender (male)	0.624 (0.343-1.138)	0.124		Gender (male)	0.899 (0.484-1.667)	0.734
		Location (right-sided)	0.857 (0.474-1.549)	0.609		Location (right-sided)	0.686 (0.371-1.270)	0.231
		TNM stage (III/IV)	2.647 (1.109-6.320)	0.028		TNM stage (III/IV)	3.208 (1.236-8.330)	0.017
		MUC2 positive	0.936 (0.368-2.379)	0.890		MUC2 positive	1.009 (0.357-2.850)	0.987
		MUC5AC positive	0.433 (0.237-0.793)	0.007		MUC5AC positive	0.599 (0.323-1.112)	0.105
		dMMR	0.373 (0.164-0.847)	0.018		dMMR	0.352 (0.153-0.810)	0.014
	Multivariate analysis				Multivariate analysis
		TNM stage (III/IV)	1.698 (0.672-4.289)	0.263		TNM stage (III/IV)	2.385 (0.886-6.421)	0.085
		MUC5AC positive	0.586 (0.307-1.117)	0.104		dMMR	0.466 (0.195-1.111)	0.085
		dMMR	0.228 (0.260-1.308)	0.175

WMDA: Well-to-moderately differentiated adenocarcinoma; PDA: Poorly differentiated adenocarcinoma; dMMR: Mismatch-repair deficiency; TNM: Tumor node metastasis; MUC: Mucin.