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

doi:10.3748/wjg.v19.i25.3957

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World Journal of Gastroenterology

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

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World J Gastroenterol. Jul 7, 2013; 19(25): 3957-3968
Published online Jul 7, 2013. doi: 10.3748/wjg.v19.i25.3957

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)
Gender	Female	24 (38.1)	46 (50.5)	35 (43.2)	9 (60.0)
Age (yr)	Range	32-87	35-92	26-90	30-82
Age (yr)	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)
Location	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)
Depth	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
Gender	Female	11 (17.5)	13 (20.6)	0.537	42 (46.1)	4 (4.4)	1.000	3 (3.7)	32 (39.5)	0.311
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
Locus	Left-sided	22 (34.9)	21 (33.3)	0.932	36 (39.6)	2 (2.2)	0.461	3 (3.7)	37 (45.7)	0.359
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
Venous invasion	No	8 (12.7)	7 (11.1)	1.000	11 (12.2)	2 (2.2)	0.325	1 (1.2)	39 (48.1)	0.616
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
Lymphatic invasion	No	11 (17.5)	17 (27.0)	0.102	6 (6.7)	2 (2.2)	0.148	3 (3.7)	26 (32.1)	1.000
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
Nodal metastasis	No	12 (19.0)	17 (27.0)	0.167	16 (18.2)	3 (3.4)	0.362	2 (2.5)	40 (50.6)	1.000
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
TNM stage	III/IV	20 (31.7)	14 (22.2)	0.167	68 (75.5)	5 (5.6)	0.171	2 (2.5)	37 (46.8)	1.000
dMMR	Yes	ND			16 (17.6)	3 (3.3)	0.356	ND
dMMR	No	ND			67 (73.6)	5 (5.5)	0.356	ND
		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
Gender	Female	18 (28.6)	6 (9.5)	0.677	22 (24.2)	24 (26.3)	0.919	14 (17.3)	21 (25.9)	0.371
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
Locus	Left-sided	34 (54.0)	9 (14.3)	0.410	24 (26.4)	14 (15.4)	0.017	25 (30.9)	15 (18.5)	0.003
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
Venous invasion	No	10 (15.9)	5 (7.9)	0.757	6 (6.7)	7 (7.8)	1.000	21 (25.9)	19 (23.5)	0.224
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
Lymphatic invasion	No	18 (28.6)	10 (15.9)	0.560	3 (3.3)	5 (5.6)	0.714	12 (14.8)	15 (18.5)	0.875
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
Nodal metastasis	No	21 (33.3)	8 (12.7)	0.892	4 (4.5)	15 (17.0)	0.010	19 (24.1)	23 (29.1)	0.950
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
TNM stage	III/IV	23 (36.5)	11 (17.5)	0.892	41 (45.6)	32 (35.6)	0.010	18 (22.8)	21 (26.6)	0.918
dMMR	Yes	ND			3 (3.3)	16 (17.6)	0.003	ND
dMMR	No	ND			41 (45.1)	31 (34.1)	0.003	ND

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.

Citation: Imai Y, Yamagishi H, Fukuda K, Ono Y, Inoue T, Ueda Y. Differential mucin phenotypes and their significance in a variation of colorectal carcinoma. World J Gastroenterol 2013; 19(25): 3957-3968
URL: https://www.wjgnet.com/1007-9327/full/v19/i25/3957.htm
DOI: https://dx.doi.org/10.3748/wjg.v19.i25.3957