ARE CDX2, BETA-CATENIN AND WNT IMMUNOMARCHERS USEFUL FOR EVALUATING THE CHANCE OF DISEASE PROGRESSION OR EVOLUTION TO DEATH IN PATIENTS WITH COLORECTAL CANCER?

Colorectal cancer (CRC) is one of the most common types of cancer in the world. Over time, intestinal epithelial cells undergo mutations that may lead to proliferative advantage and the emergence of cancer. Mutations in the beta-catenin pathway are amongst those described in the development of CRC.

Aim:

To verify the existence of a relation between the presence of Wnt3, beta-catenin and CDX2 in colorectal cancer samples and clinical outcomes such as disease progression or death.

Method:

Wnt3a, beta-catenin and CDX2 immunohistochemistry was performed on CRC tissue microarray samples (n=122), and analysis regarding the relation between biomarker expression and disease progression or death was performed.

Results:

No significant difference was found between the presence or absence of CDX2, beta-catenin or Wnt3a expression and clinical stage, tumor grade, disease progression or death.

Conclusion:

CDX2, beta-catenin and Wnt3a are not useful to predict prognosis in patients with CRC.

HEADINGS:
CDX2; Beta-catenin; Wnt3; Colorectal cancer

	n	%
Age at diagnosis
<50 anos	22	18
50-70 anos	69	56.5
>70 anos	31	25.4
UICC (clinical stage)
0, I ou II	48	39.3
III e IV	74	60.7
Degree of differentiation
Poorly differentiated	10	8.2
Moderately differentiated	101	82.8
Well differentiated	8	6.6
Indeterminate	3	2.5
Total	122	100

Marker		n	%
CDX2	negative	25	20.5
	positive	82	67.2
	inconclusive	15	12.3
Beta-catenin	negative	56	45.9
	positive	52	42.6
	inconclusive	14	11.5
WNT3a	negative	50	41
	positive	53	43.4
	inconclusive	19	15.6
Total		122	100

Variable	Classification	n	% of cases with progression	p*	SHR	CI 95%
Age at diagnosis	<50 (ref)	22	10 (45.5)
	50 a 70	69	25 (36.2)	0.225	0.64	0.31-1.31
	>70	31	8 (25.8)	0.143	0.49	0.20-1.27
Gender	Fem (ref)	59	16 (27.1)
Gender	Male	63	27 (42.9)	0.127	1.63	0.87-3.04
Degree of differentiation (excluded “indet”)	Poorly differentiated (0)	10	1 (10.0)
	Well differentiated (ref) (2)	8	3 (37.5)	0.241	3.46	0.44-27.5
	Moderate (1)	101	39 (38.6)	0.360	2.90	0.30-28.2
UICC	0/I/II	48	15 (31.2)
UICC	III/IV	74	28 (37.8)	0.085	1.68	0.93-3.05
CDX2	Negative (ref)	25	9 (36.0)
	Positive	82	28 (34.1)	0.982	0.99	0.47-2.08
	Inconclusive	15	6 (40.0)	0.489	1.46	0.50-4.26
Beta-catenin	Negative (ref)	56	18 (32.1)
	Positive	52	21 (40.4)	0.610	1.18	0.63-2.20
	Inconclusive	14	4 (28.6)	0.902	1.08	0.34-3.43
Wnt3	Negative (ref)	50	20 (40.0)
	Positive	53	17 (32.1)	0.094	0.58	0.30-1.10
	Inconclusive	19	6 (31.6)	0.364	0.66	0.25-1.63

Variable	Classification	n	% death	p*	HR	CI 95%
Age at diagnosis	<50 (ref)	22	9 (40.9%)
	50 a 70	69	42 (60.9%)	0.361	1.40	0.68-2.88
	>70	31	17 (54.8%)	0.099	1.98	0.88-4.45
Genre	Male (ref)	63	32 (50.8%)
Genre	Fem	59	36 (61.0%)	0.134	1.44	0.89-2.34
Degree of differentiation (excluded “indet”)	Well differentiated (ref) (2)	8	2 (25.0%)
	Moderate (1)	101	58 57.4%)	0.078	3.55	0.87-14.6
	Poorly differentiated (0)	10	7 (70.0%)	0.001	17.6	3.5-88.6
UICC (grouped)	0/I/II	48	22 (45.8%)
UICC (grouped)	III/IV	74	46 (62.2%)	<0.001	2.52	1.49-4.25
Progression event	No	79	41 (51.9)
Progression event	Yes	43	27 (62.8)	<0.001	5.91	3.37-10.4
CDX2	Negative (ref)	25	9 (36.0%)
	Positive	82	28 (34.1%)	0.373	1.33	0.71-2.51
	Inconclusive	15	6 (40.0%)	0.855	1.10	0.41-2.94
Beta-catenin	Negative (ref)	56	28 (50.0%)
	Positive	52	35 (67.3%)	0.480	1.20	0.73-1.97
	Inconclusive	14	5 (35.7%)	0.791	0.88	0.34-2.28
Wnt3	Negative (ref)	50	30 (60.0%)
	Positive	53	30 (56.6%)	0.204	0.72	0.43-1.20
	Inconclusive	19	8 (42.1%)	0.268	0.64	0.29-1.40

Colégio Brasileiro de Cirurgia Digestiva Av. Brigadeiro Luiz Antonio, 278 - 6° - Salas 10 e 11, 01318-901 São Paulo/SP Brasil, Tel.: (11) 3288-8174/3289-0741 - São Paulo - SP - Brazil
E-mail: revistaabcd@gmail.com

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[1] Correspondence Fabiola Pabst Bremer E-mail: fabiolabremer@outlook.com