Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?

Table 1 Mammalian vascular endothelial growth factor family of ligands

	Receptor	Chromosomal location	Angiogenesis	Lymphangiogenesis
VEGF	VEGFR1, VEGFR2, NRP1	6p23.1	+	Conflicting data1
VEGF-B	VEGFR1, NRP1	11q13	Conflicting data	-
PIGF	VEGFR1 NRP1, NRP2	14q24	Modest	Not determined
VEGF-C	VEGFR2 VEGFR3 NRP2	4q34	Modest	+
VEGF-D	VEGFR2 VEGFR3	Xp22.31	Modest	+

¹Indirect lymphangiogenic effect, by recruiting VEGF-C and VEGF-D producing macrophages[15]. Lymphangiogenesis via alternative, VEGFR3-independe pathway[16].

Table 2 Studies on circulating VEGF-C/D in human solid malignancies (clinicopathological association)

Tumor	Marker	Sample	Cases (n)	LNM	Prognostic impact	Ref.
Gastric cancer	VEGF-C	Serum	80	P = 0.001	P = 0.001	67
Esophageal cancer	VEGF-C	Serum	70	P = 0.022	ND	102
Esophageal cancer	VEGF-C	Serum	73	( + )1	ND	103
Colorectal cancer	VEGF-D	Plasma	59	(-)	ND	38
Colorectal cancer	VEGF-C	Plasma	41	( + )2	ND	144
Colorectal cancer	VEGF-C	Plasma	120	(-)	ND	145
	VEGF-D			(-)
Colorectal cancer	VEGF-C	Serum	66	( + )	ND	146
Breast cancer	VEGF-D	Plasma	51	(-)	ND	46
Breast cancer	VEGF-C	Plasma	122	(-)	(-)	47
Breast cancer3	VEGF-D	Plasma	142			48
Nsc4 lung cancer	VEGF-C	Serum	92	P = 0.0260	ND	49
Nsc lung cancer	VEGF-C	Serum	78	P = 0.0004	ND	50
Nsc lung cancer	VEGF-C	Serum	116	P = 0.0007	ND	51
Cervical cancer	VEGF-C	Serum	78	P = 0.0001	P = 0.0112	52
Cervical cancer	VEGF-C	Serum	205	( + )2	( + )2	53
Prostate cancer	VEGF-D	Plasma	30	P = 0.0043	ND	54
HNSCC5	VEGF-C	Plasma	46	(-)	(-)	55

ND: Not determined;

¹Indirect result;

²None statistically significant;

³Post-treatment study;

⁴Non small cell;

⁵Head and Neck Squamous Cell Carcinoma.