Association between VEGF expression in tumour-associated macrophages and elevated serum VEGF levels in primary colorectal cancer patients.
OBJECTIVE
Angiogenesis is stimulated by angiogenic factors released by tumour cells, though other cells, such as tumour-associated macrophages (TAMs), also contribute towards increasing the angiogenic process in colorectal cancer (CRC). The aim of this study was to determine in CRC patients the contribution of vascular endothelial growth factor (VEGF) expression in TAMs and tumour cells towards circulating VEGF levels, their association with p53 expression and microvascular density (MVD), and their prognostic value.


METHODS
Immunohistochemical techniques were used to identify TAMs and p53 protein, and to evaluate the VEGF expression in TAMs, MVD and tumour cells in 110 primary CRC patients. Serum VEGF levels were determined using an enzyme immune assay.


RESULTS
There was a greater expression of VEGF in tumours with a positive p53 expression than a negative stain (p<0.01). The macrophage index was not related to tumour VEGF secretion. No significant association was observed between serum VEGF levels and VEGF tumour expression, node status, histological grade, MVD or p53 expression. However, the patients with high values of VEGF expression in TAMs showed significantly higher presurgery serum VEGF levels than those patients with low values of VEGF expression in TAMs (p=0.021). No statistical significant differences in survival were found when we compared patients with high VEGF expression in TAMs vs low or median VEGF expression in TAMs (p=0.093). Serum VEGF levels were increased 6-8 hours after tumour removal (p=0.001).


CONCLUSIONS
Our data suggest that in primary CRC, presurgery circulating VEGF levels are related to VEGF produced by TAMs.
Medical Oncology Service, Virgen de Victoria University Hospital, E-29010 Malaga, Spain. fjgonzalez02@yahoo.es
Francisco J
FJ
Gonzalez
Luis
L
Vicioso
Martina
M
Alvarez
Isabel
I
Sevilla
Eduardo
E
Marques
Elena
E
Gallego
Lorenzo
L
Alonso
Alfredo
A
Matilla
Emilio
E
Alba
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000097:blood* / Q000098:blood supply / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A