Pathological risk factors for lymph node metastasis in patients with submucosal invasive colorectal carcinoma

Figures & data

Figure 1 p53 expression pattern was associated with tumor budding status in T1 CRC patients.

Note: (Top) Tumor with many buds at the invasive front (A) positively expressed of p53 (B). (Bottom) Tumors with negative budding status at the invasive front (C) barely expressed p53 (D).

Abbreviation: CRC, colorectal carcinoma.

Table 1 Relationship between histopathological factors and LNM in submucosal invasive colorectal carcinoma

Clinicopathological feature		LNM (–) %	LNM (+) %	χ^2	P-value
Age (years)	<60	118 (48)	22 (49)	0.008	0.929
	≥60	127 (52)	23 (51)
Gender	Female	112 (46)	27 (60)	3.109	0.078
	Male	133 (54)	18 (40)
Location	Right-sided	28 (11)	11 (24)	5.547	0.062
	Left-sided	49 (20)	8 (18)
	Rectum	168 (69)	26 (58)
Size (cm)	<2	105 (43)	20 (44)	0.039	0.843
	≥2	140 (57)	25 (56)
MM status	Identifiable	57 (23)	8 (18)	0.658	0.417
	Unidentifiable	188 (77)	37 (82)
Submucosal invasive depth (μm, all cases)	<1,000	66 (27)	7 (16)	2.615	0.106
	≥1,000	179 (73)	38 (84)
Submucosal invasive depth (μm, non-pedunculated cases)	<1,000	45 (32)	4 (13)	2.615	0.043
	≥1,000	97 (68)	26 (87)
Submucosal invasive depth (μm, pedunculated cases)	<1,000	21 (20)	3 (20)	0.001	0.972
	≥1,000	82 (80)	12 (80)
Precursor adenoma	Absent	49 (20)	11 (24)	0.458	0.499
	Present	196 (80)	34 (76)
Tumor growth pattern	Non-pedunculated	142 (58)	30 (67)	1.194	0.274
	Pedunculated	103 (42)	15 (33)
CEA	Normal	233 (95)	40 (89)	0.103	0.156
	High	12 (5)	5 (11)
Tumor differentiation grade	Low	216 (88)	22 (49)	39.849	<0.001
	High	29 (12)	23 (51)
LVI	Absent	211 (86)	28 (62)	14.983	<0.001
	Present	34 (14)	17 (38)
Budding status	Negative	200 (82)	26 (58)	12.579	<0.001
	Positive	45(18)	19 (42)
Border configuration	Expanding	82 (33)	8 (18)	4.374	0.036
	Infiltrative	163 (67)	37 (82)

Note: Bold value indicates P<0.05.

Abbreviations: CEA, carcinoembryonic antigen; CRC, colorectal carcinoma; LNM, lymph node metastasis; LVI, lymphovascular invasion; MM, muscularis mucosae.

Table 2 Univariate and multivariate risk analysis of lymph node metastasis in submucosal invasive colorectal carcinoma

Variable	Univariate analysis			Multivariate analysis
	HR	95% CI	P-value	HR	95% CI	P-value
Tumor grade	7.787	3.862–15.702	<0.001	6.315	3.042–13.110	<0.001
Lymphovascular invasion	3.768	1.865–7.611	<0.001	2.505	1.152–5.448	0.021
Budding status	3.248	1.655–6.374	0.001	2.308	1.056–5.047	0.036
Border configuration	2.327	1.036–5.225	0.041	1.252	0.494–3.169	0.636

Note: Bold value indicates P<0.05.

Figure 2 ROC curves of the three adverse factors.

Note: The combination of these three factors provided the highest AUC value (AUC: 0.76), indicating optimal predictive ability of LNM status.

Abbreviations: AUC, area under the curve; LNM, lymph node metastasis; ROC, receiver operator characteristic.

Table 3 Correlation between MMR and p53 expression and clinicopathological features in submucosal invasive colorectal carcinoma

Variable		MMR			p53 expression
		pMMR	dMMR	χ^2	P	Absent	Present	χ^2	P
Lymph nodal status	Negative	203	42	0.214	0.644	83	162	0.897	0.343
	Positive	36	9			12	33
Tumor differentiation grade	Low	194	44	0.744	0.388	75	163	0.936	0.333
	High	45	7			20	32
Lymphovascular invasion	Absent	193	46	2.586	0.108	80	159	0.315	0.575
	Present	46	5			15	36
Budding status	Negative	181	45	3.820	0.051	81	145	4.416	0.036
	Positive	58	6			14	50

Note: Bold value indicates P<0.05.

Abbreviations: dMMR, mismatch repair protein deficient; MMR, mismatch repair; pMMR, mismatch repair protein proficient.

Figure 3 Kaplan–Meier DFS curve of T1 CRC patients with different lymph node statuses (A) (negative, n=245 vs positive, n=45) or numbers of adverse features (B). Cases with ≤2 adverse features (n=283 vs cases with 3 adverse features, n=7).

Abbreviations: CRC, colorectal carcinoma; DFS, disease-free survival.