Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases

Table 1 RAS and BRAF status and patient demographics

			BRAF		BRAF		P	RAS		RAS		P
	All		MT		WT			MT		WT
	n	%	n	%	n	%		n	%	n	%
Age	< 60	87	50	5	6	82	94	1.00	44	51	43	49	1.00
	≥ 60	87	50	6	7	81	93		43	49	44	51
Gender	Male	103	59	3	3	100	97	0.052	49	48	54	52	0.54
	Female	71	41	8	11	63	89		38	54	33	46
Race	White	122	70	7	6	115	94	0.53	57	47	65	53	0.015
	Asian, PI	41	24	4	10	37	90		23	56	18	44
	Black	8	5	0	--	8	100		7	87	1	13
	Unknown	3	2	0	--	3	100		0	--	3	100

n: Number of patients; PI: Pacific Islander; MT: Mutant; WT: Wild type.

Table 2 RAS and BRAF status and primary tumor location and pattern of metastasis

			BRAF		BRAF		P	RAS		RAS		P
	All		MT		WT			MT		WT
	n	%	n	%	n	%		n	%	n	%
Primary lesion	Rectal	43	25	0	--	43	100	0.022	23	53	20	47	0.23
	Left colon	79	45	5	6	74	94		34	43	45	57
	Right colon	52	30	6	12	46	88		30	58	22	42
Site of metastasis	Lung	72	42	3	4	69	96	0.36	41	57	31	42	0.17
	Liver	98	56	5	5	93	95	0.54	46	47	52	53	0.44
	Peritoneal	49	28	5	10	44	90	0.3	23	47	26	53	0.74

n: Number of patients; MT: Mutant; WT: Wild type.

Table 3 RAS and BRAF status and carcinoembryonic antigen levels

			BRAF		BRAF		P	RAS		RAS		P
	All		MT		WT			MT		WT
	n	%	n	%	n	%		n	%	n	%
< 5 ng/mL	60	34	4	7	56	93	1.00	37	62	23	38	0.037
≥ 5 ng/mL	114	66	7	6	107	94		64	56	50	44

n: Number of patients; MT: Mutant; WT: Wild type.

Table 4 BRAF status and pattern of colon cancer metastases

Ref.	n (%BRAF)	End point	%BRAF MT vs %BRAF WT	P
Tran et al[8]	524 (11%)	Rate of peritoneal metastases	46% vs 24%	0.001
		Rate of distant lymph node metastases	53% vs 38%	0.008
		Rate of lung metastases	35% vs 49%	0.049
Yaeger et al[9]	515 (18%)	Peritoneal involvement at presentation	26% vs 14%	< 0.01
Kawazoe et al[12]	264 (5%)	Peritoneal metastasis	50% vs 18%	0.009

n: Total number of patients; %BRAF: %patients with BRAF mutation; MT: Mutant; WT: Wild type.

Table 5 RAS status and pattern of colon cancer metastases

Ref.	n (%MT)	Results	P
Cejas et al[29]	110 (34% KRAS MT)	Frequency of KRAS mutation	0.054
		in primary tumor of patients with lung vs liver metastases
		59% vs 32%
Tie et al[10]	Cohort A	Mutation frequencies	0.003
	161 (48.4% KRAS MT)	in lung in KRAS MT vs WT
		62% vs 38%
		Mutation frequencies in brain	0.003
		in KRAS MT vs WT
		56.5% vs 43.5%
	Cohort C	Relapse in lung in KRAS MT	0.007
	859 (33.8% KRAS MT)	HR 2.1, 95%CI: 1.2-3.5
Kim et al[23]	143 (43.4% KRAS MT)	Lung as initial metastatic site in KRAS MT vs WT	0.003
		45.3% vs 22.1%
		Liver as initial metastatic site in KRAS MT vs WT	< 0.001
		37.3% vs 70.6%
		Distant lymph node as initial metastatic site in KRAS MT vs WT	0.025
		6.7% vs 19.1%
Vauthey et al[25]	193 (18% All RAS MT)	3-yr lung RFS rate in patients undergoing curative resection of liver metastases in RAS MT vs WT	< 0.001
		34.6% vs 59.3%
Yaeger et al[11]	918 (48% All RAS MT)	Lung as site of first metastasis	< 0.01
		in RAS MT vs WT
		22% vs%
		Cumulative incidence of lung as subsequent metastasis at 2 yr after diagnosis in RAS MT vs WT	< 0.001
		32.5% vs 19%
Kemeny et al[24]	169 (30% KRAS MT)	3-yr cumulative recurrence rate to lung after hepatic resection and HAI in KRAS MT vs WT	< 0.01
		58% vs 32%	0.05
		3-yr cumulative recurrence rate to brain after hepatic resection and HAI in KRAS MT vs WT
		14.5% vs 2%	< 0.01
		3-yr cumulative recurrence rate to bone after hepatic resection and HAI in KRAS MT vs WT
		13.4% vs 2%	0.002
Pereira et al[13]	494 (41% KRAS MT)	Time to lung metastasis (median months) in KRAS MT vs WT
		15.2 vs 22.4 (HR 1.4)

n: Total number of patients; %MT: %patients with mutation; MT: Mutant; WT: Wild type; RFS: Recurrence free survival; HAI: Hepatic arterial infusion.