Histologic features and genomic alterations of primary colorectal adenocarcinoma predict growth patterns of liver metastasis

Table 1 Main clinical demographics and histological growth patterns in patients with colorectal carcinoma and liver metastasis in the study

Case No.	Liver metastasis growth pattern	Primary colorectal growth pattern	Tumor budding score	Crohn's disease-like appearance	Liver metastasis (mo)	Follow-up (mo)	Prognosis	Major mutations
1	DGP	EGP	L	+	16	57	Alive without tumor	APC, KRAS, BRCA2
2	DGP	IGP	M	-	6	25	Alive with bone metastasis	NA
3	DGP	IGP	H	-	46	52	Alive with liver metastasis	NA
4	DGP	EGP	M	+	25	33	Alive with liver metastasis	APC, KRAS, PIK3CA, BRCA1
5	DGP	EGP	L	+	39	46	Alive without tumor	NA
6	DGP	IGP	L	-	8	33	Alive with liver metastasis	NA
7	DGP	IGP	L	+	25	32	Alive without tumor	NA
8	DGP	EGP	L	-	6	44	Alive with tubular adenoma	APC, TP53, PIK3CA
9	DGP	EGP	L	-	12	28	Alive without tumor	NA
10	DGP	EGP	L	+	7	21	Alive without tumor	NA
11	DGP	EGP	L	-	7	16	Alive without tumor	APC, TP53, FAT4, BRAF
12	DGP	IGP	M	+	5	25	Alive without tumor	NA
13	DGP	IGP	L	+	6	42	Alive without tumor	NA
14	DGP	EGP	M	-	38	54	Alive with lung metastasis	NA
15	DGP	EGP	L	-	17	20	Alive without tumor	TP53, DNAH5, FAT4
16	RGP	IGP	H	-	2	17	Alive without tumor	DNAH5, KRAS, FAT4
17	RGP	IGP	H	-	5	72	Alive without tumor	NA
18	RGP	IGP	H	-	16	63	Died of liver metastasis	NA
19	RGP	IGP	L	-	9	35	Alive without tumor	NA
20	RGP	IGP	H	-	25	58	Alive without tumor	NA
21	RGP	EGP	L	-	6	23	Alive without tumor	NA
22	RGP	IGP	M	-	28	48	Alive without tumor	APC, TP53, SMAD4
23	RGP	IGP	H	-	40	60	Alive without tumor	APC, CTNNB1
24	RGP	IGP	M	-	6	17	Died of liver metastasis	NA
25	RGP	IGP	M	-	6	33	Died of liver metastasis	APC, TP53, KRAS, ERBB2, ERBB3
26	RGP	EGP	L	+	7	41	Died of liver metastasis	NA
27	RGP	IGP	H	-	5	35	Died of brain metastasis	NA
28	RGP	IGP	L	-	27	32	Died of liver metastasis	NA
29	RGP	IGP	H	-	3	12	Alive without tumor	TP53, LRP2, SDK1

DGP: Desmoplastic growth pattern; EGP: Expanding growth pattern; IGP: Infiltrating growth pattern; RGP: Replacement growth pattern; L: Low; M: Intermediate; H: High; NA: Not available.

Table 2 Association between clinicopathological characteristics and growth patterns

Characteristic		Group A	Group B	P-value
Sex	Male	9	10	0.6999
	Female	6	4
Age	Mean ± SD	67.5 ± 9.6	62.3 ± 13.6	0.2774
	Median	67	60.5
	Range	50-82	43-82
Serum CEA level	Mean ± SD	15.5 ± 25.2	46.9 ± 148.7	0.3823
(μg/L)	Median	3.7	5.65
	Range	0.9-88.0	1.1-563.2
Localization	Cecum	3	3	0.6621
	Ascending	2	0
	Transverse	1	1
	Descending	1	0
	Sigmoid	2	3
	Rectum	6	7
Size (cm)	Mean ± SD	4.2 ± 1.3	4.3 ± 2.4	0.5814
	Median	4.6	4
	Range	2.0-6.0	2.0-11.0
Configuration	Exophytic	7	7	0.2643
	Endophytic	8	5
	N/A	0	2
Histologic grade	G1	5	7	0.3060
	G2	8	7
	G3	2	0
Tumor depth	T1	0	0	0.6999
	T2	0	0
	T3	9	10
	T4	6	4
Lymph node metastasis	Positive	9	10	0.6999
	Negative	6	4
Tumor budding score (TBS)	High	1	7	0.0275
	Intermediate	4	3
	Low	10	4
	Negative	0	0
Tumor deposits	Positive	3	4	0.6817
	Negative	12	10
Lymphovascular invasion	Positive	11	12	0.6513
	Negative	4	2
Perineural invasion	Positive	10	12	0.3898
	Negative	5	2
Peri-tumoral inflammatory cell band	Negative	5	4	0.5974
	Low grade	8	6
	High grade	2	4
Crohn’s disease-like response	Positive	7	1	0.0352
	Negative	8	13
Histologic growth pattern	EGP	9	2	0.0209
	IGP	6	12

SD: Standard deviation; CEA: Carcinoembryonic antigen; NA: Not available; EGP: Expanding growth pattern; IGP: Infiltrating growth pattern.

Table 3 Value of selected pathological characteristics in predicting the histological growth patterns of colorectal carcinoma liver metastasis

Pathological characteristic	Value	Group A	Group B
HGP	SE% (CI)	60.0 (35.8-80.2)	85.7 (60.1-97.5)
	SF% (CI)	85.7 (60.1-97.5)	60.0 (35.8-80.2)
	PPV% (CI)	81.8 (52.3-96.8)	66.7 (43.8-83.7)
	NPV% (CI)	66.7 (43.8-83.7)	81.8 (52.3-96.8)
TBS	SE% (CI)	66.7 (41.7-84.8)	71.4 (45,4-88.3)
	SF% (CI)	71.4 (45,4-88.3)	66.7 (41.7-84.8)
	PPV% (CI)	71.4 (45.4-88.3)	66.7 (41.7-84.8)
	NPV% (CI)	66.7 (41.7-84.8)	71.4 (45.4-88.3)
CDR	SE% (CI)	46.7 (24.8-69.9)	92.9 (68.5-99.6)
	SF% (CI)	92.9 (68.5-99.6)	46.7 (24.8-69.9)
	PPV% (CI)	87.5 (52.9-99.4)	61.9 (40.9-79.3)
	NPV% (CI)	61.9 (40.9-79.3)	87.5 (52.9-99.4)
HGP + TBS	SE% (CI)	80.0 (54.8-93.0)	85.7 (60.1-97.5)
	SF% (CI)	71.4 (45.4-88.3)	46.7 (24.8-69.9)
	PPV% (CI)	75.0 (50.5-89.8)	60.0 (38.7-78.1)
	NPV% (CI)	76.9 (49.7-91.8)	77.8 (45.3-96.1)
HGP + CDR	SE% (CI)	80.0 (54.8-93.0)	92.9 (68.5-99.6)
	SF% (CI)	85.7 (60.1-97.5)	26.7 (10.9-52.0)
	PPV% (CI)	85.7 (60.1-97.6)	54.2 (35.1-72.1)
	NPV% (CI)	80.0 (54.8-93.0)	80.0 (37.6-99.0)
TBS + CDR	SE% (CI)	80.0 (54.8-93.0)	92.9 (68.5-99.6)
	SF% (CI)	71.4 (45.4-88.3)	33.3 (15.2-58.3)
	PPV% (CI)	75.0 (50.5-89.8)	56.5 (36.8-74.4)
	NPV% (CI)	76.9 (49.7-91.8)	83.3 (43.7-99.2)
HGP + TBS + CDR	SE% (CI)	86.7 (62.1-97.6)	92.9 (68.5-99.6)
	SF% (CI)	71.4 (45.4-88.3)	20.0 (7.0-45.2)
	PPV% (CI)	76.5 (52.7-90.4)	52.0 (33.5-70.0)
	NPV% (CI)	83.3 (55.2-97.0)	75.0 (30.1-98.7)

HGP: Histological growth pattern; 95%CI: 95% confidence interval; SE: Sensitivity; SF: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; TBS: Tumor budding score; CDA: Crohn’s disease-like appearance.