Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer

Table 1 LN Metastasis in relation to clinicopathologic features of submucosal CRC

Clinicopathologic	features	n	LN positive (%)	P value
Size (mm)	≤ 20	159	20 (12.6)	NS
	> 20	55	8 (14.6)
Location	Rectum	61	8 (13.1)	NS
	Colon	153	20 (13.1)
Macroscopic type	Protruded type	145	14 (9.7)	0.0311
	Superficial type	69	14 (20.3)
Depth of invasion (μm)	< 1000	25	1 (4.0)	NS
	≥ 1000	189	27 (14.3)
Histologic grade	Favorable	198	22 (11.1)	0.0026
	Unfavorable	16	6 (37.5)
Budding	Negative	175	13 (7.4)	< 0.0001
	Positive	39	15 (38.5)
Lymphatic	Negative	148	12 (8.1)	0.0012
involvement1	Positive	66	16 (24.2)
Venous involvement	Negative	166	20 (12.1)	NS
	Positive	48	8 (16.7)
Number of LNs	≤ 15	128	16 (12.5)	NS
examined	> 15	86	12 (14.0)
Total		214	28 (13.1)

¹Identified by podoplanin immunostaining. NS: not significant. LN: lymph node; CRC: colorectal cancer.

Table 2 LN metastasis in relation to immunohistochemical molecular markers in submucosal CRC

Immunohistochemical	markers	n	LN positive(%)	P value
MVD	Low	88	2 (2.3)	< 0.0001
	High	126	26 (20.6)
LVD	Low	109	5 (3.8)	0.0002
	High	105	23 (18.9)
Ki-67 LI	Low	90	7 (7.8)	0.0499
	High	124	21 (16.9)
MUC1	Negative	108	5 (4.6)	0.0002
	Positive	106	23 (21.7)
Cathepsin D	Negative	85	3 (3.5)	0.0008
	Positive	129	25 (19.4)
MMP-7	Negative	103	8 (7.8)	0.0263
	Positive	111	20 (18.0)
Total			214	28 (13.1)

LN: lymph node metastasis; CRC: Colorectal cancer; MVD: microvessel density; LVD: lymphatic vessel density; MUC1: mucin 1; LI: labeling index; MMP-7: matrix metalloproteinase-7.

Table 3 Multivariate analysis of risk factors for LN metastasis of submucosal CRC

Risk factors	P value	Odds ratio
MVD-High	0.0008	16.67
Histologic grade-Unfavorable	0.0116	11.73
Cathepsin D-Positive	0.0071	8.41
LVD-High	0.0027	7.65
Macroscopic type-Superficial	0.0029	7.27
Budding-Positive	0.0160	4.36
MUC1-Positive	0.0266	3.96
Lymphatic involvement Positive	NS	-
Ki-67 LI-High	NS	-
MMP-7-Positive	NS	-

LN: lymph node metastasis; CRC: colorectal cancer: NS: not significant. MVD: microvessel density; LVD: Lymphatic vessel density; MUC1: mucin 1; LI: labeling index; MMP-7: matrix metalloproteinase-7.

Table 4 Incidence of LN metastasis of submucosal CRC in relation to MUC1 and cathepsin D expression

Cathepsin D expression	MUC1 expression
	Negative	Positive
Negative	0/49 (0)	3/36 (8.3)
Positive	5/59 (8.5)	20/70 (28.6)b

LN: lymph node metastasis; CRC: Colorectal cancer. MUC1: mucin 1. ^bP < 0.0001 vs cathepsin D negative and MUC1 negative group.

Table 5 Incidence of LN metastasis of submucosal CRC in relation to MUC1 expression and MVD

MVD	MUC1 expression
	Negative	Positive
Low	0/51 (0)	2/37 (5.4)
High	5/57 (8.8)	21/69 (30.4)b

LN: lymph node metastasis; CRC: colorectal cancer. MVD: microvessel density; MUC1: mucin 1. ^bP < 0.0001 vs MVD low and MUC1 negative group.

Table 6 Incidence of LN metastasis of submucosal CRC in relation to cathepsin D expression and MVD

MVD	MUC1 expression
	Negative	Positive
Low	0/33 (0)	2/55 (3.6)
High	3/52 (5.8)	23/74 (31.1)b

LN: lymph node metastasis; CRC: colorectal cancer. MVD: microvessel density.

^bP < 0.0001 vs MVD low and Cathepsin D negative group.

Table 7 Incidence of LN metastasis of submucosal CRC in relation to number of positive immunohistochemical markers

No. of positive markers1	n	Cases with LN metastasis (%)
0	13	0(0)
1	44	0(0)
2	76	4(5.3)
3	54	7(13.0)
4	27	17(63.0)
Total	214	28(13.1)

¹Microvessel density, cathepsin D, MUC1 and lymphatic vessel density. LN: lymph node metastasis; CRC: colorectal cancer.