Divergent expression of bacterial wall sensing Toll-like receptors 2 and 4 in colorectal cancer

Table 1 Characteristics of 118 patients with colorectal carcinoma n (%)

	Whole study group	Survival in 5-yr follow-up
Gender
Male	56 (47.5)	35 (62.5)
Female	62 (52.5)	36 (58.1)
Age, median (range)	69 (36-89)
Other morbidities
No	27 (22.9)	16 (59.3)
Yes	91 (77.1)	55 (60.4)
Other neoplasm
No	109 (92.4)	62 (56.9)
Sex organs or breast cancer	2 (1.7)	2 (100.0)
Other cancer	3 (2.5)	3 (100.0)
Colon adenoma	4 (3.4)	4 (100.0)
Cancer in family
No/not known	104 (88.1)	59 (56.7)
CRC	8 (6.8)	7 (87.5)
HNPCC family	2 (1.7)	2 (100.0)
Other HNPCC-associated cancer	3 (2.5)	2 (66.7)
Other cancer	1 (0.8)	1 (100.0)
Type of operation
Radical1	94 (80.3)	69 (73.4)
Palliative2	23 (19.7)	2 (8.7)
Location of tumour
Proximal colon	46 (39.0)	27 (58.7)
Distal colon	39 (33.1)	25 (64.1)
Rectum	32 (27.1)	18 (56.3)
Multiple tumours	1 (0.8)	1 (100.0)

¹Radically operated distant metastases in a second operation in one case;

²Metastases treated non-operatively in two cases (both alive at 5-year follow-up).

Table 2 Tumour features n (%)

	Whole study group	Survival in 5-yr follow-up
Stage
I	18 (15.3)	15 (83.3)
II	48 (40.7)	37 (77.1)
III	30 (25.4)	16 (53.3)
IV	22 (18.6)	3 (13.6)
Grade
I	17 (14.4)	13 (76.5)
II	86 (72.9)	53 (61.6)
III	14 (11.9)	5 (35.7)
Data missing	1 (0.8)	0 (0)
Lymph node metastasis
No	72 (61.0)	53 (73.6)
Yes	46 (39.0)	18 (39.1)
Distant metastasis
No	96 (81.4)	68 (70.8)
Yes	22 (18.6)	3 (13.6)
Mucinous carcinoma
No	99 (83.9)	59 (59.6)
Yes	10 (8.5)	6 (60.0)
Data missing	9 (7.6)

Table 3 Mean intensities and histoscores of immunostaining

	TLR2 intensity, mean ± SD	P value	TLR2 histoscore, mean ± SD	P value	TLR4 intensity, mean ± SD	P value	TLR4 histoscore, mean ± SD	P value
Invasive front	2.3 ± 0.6	< 0.001	224 ± 67	< 0.001	2.2 ± 0.6	< 0.001	223 ± 66	0.024
Normal mucosa	1.4 ± 0.7		129 ± 72		2.6 ± 0.6		243 ± 77
Invasive front	2.2 ± 0.7	0.006	210 ± 77	0.054	2.2 ± 0.6	0.060	216 ± 68	0.048
Lymph node	1.8 ± 0.7		180 ± 72		2.4 ± 0.7		241 ± 70
Tumour bulk	2.3 ± 0.6	< 0.001	224 ± 65	< 0.001	2.0 ± 0.7	< 0.001	197 ± 73	< 0.001
Normal mucosa	1.4 ± 0.7		129 ± 72		2.6 ± 0.6		244 ± 78
Tumour bulk	2.2 ± 0.6	0.007	216 ± 65	0.011	2.0 ± 0.6	0.001	194 ± 69	0.001
Lymph node	1.8 ± 0.7		180 ± 72		2.4 ± 0.7		241 ± 70
Lymph node	1.8 ± 0.7	0.011	179 ± 70	0.003	2.4 ± 0.7	0.017	238 ± 70	0.40
Normal mucosa	1.4 ± 0.7		127 ± 71		2.7 ± 0.5		251 ± 72
Invasive front	2.3 ± 0.6	0.55	225 ± 66	> 0.9	2.3 ± 0.6	< 0.001	223 ± 66	< 0.001
Tumour bulk	2.3 ± 0.6		225 ± 64		2.0 ± 0.7		197 ± 73

Mean values vary due to missing samples. TLR: Toll-like receptor.

Table 4 Comparison of mean intensities of immunostainings between toll-like receptors 2 and 4

	Intensity, mean ± SD	P value	Histoscore, mean ± SD	P value	n
Tumour bulk
TLR2	2.3 ± 0.6	< 0.001	225 ± 64	< 0.001	117
TLR4	2.0 ± 0.7		198 ± 73		117
Invasive front
TLR2	2.3 ± 0.6	0.55	225 ± 66	0.83	116
TLR4	2.3 ± 0.6		223 ± 66		116
Lymph node
TLR2	1.8 ± 0.7	< 0.001	180 ± 71	< 0.001	43
TLR4	2.4 ± 0.7		241 ± 70		43
Normal mucosa
TLR2	1.4 ± 0.7	< 0.001	129 ± 72	< 0.001	114
TLR4	2.6 ± 0.6		243 ± 79		114

N values vary due to missing samples. TLR: Toll-like receptor.

Table 5 5-year cancer-specific survival in percent (number of cases) vs intensity of staining in the tumour bulk, invasive front, and lymph node metastases n (%)

		Intensity of staining	Whole colon	P value1	Proximal colon	P valu1	Distal colon and rectum	P value1
TLR2	Tumour bulk	Weak	14 (63.6)	0.43	4 (66.7)	0.65	9 (60.0)	0.33
		Strong	71 (74.7)		29 (74.4)		42 (75.0)
	Invasive front	Weak	14 (73.7)	> 0.9	6 (66.7)	0.68	8 (80.0)	0.71
		Strong	70 (72.2)		27 (75.0)		42 (70.0)
	Lymph node	Weak	9 (50.0)	0.55	3 (37.5)	> 0.9	6 (60.0)	0.26
		Strong	10 (40.0)		3 (42.9)		6 (35.3)
TLR4	Tumour bulk	Weak	25 (65.8)	0.27	7 (63.6)	0.45	18 (66.7)	0.59
		Strong	60 (75.9)		26 (76.5)		33 (75.0)
	Invasive front	Weak	17 (63.0)	0.33	5 (45.5)	0.044	12 (75.0)	> 0.9
		Strong	67 (75.3)		28 (82.4)		38 (70.4)
	Lymph node	Weak	2 (25.0)	0.27	0 (0.0)	0.23	2 (40.0)	> 0.9
		Strong	17 (48.6)		6 (50.0)		10 (45.5)

¹χ² test/Fisher’s exact test. N values vary due to missing samples; One case with multiple tumours excluded from location-based analysis; Weak intensity < 2 and strong intensity ≥ 2.