The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer.
OBJECTIVE
It has been suggested that colorectal neoplasms with or without microsatellite instability (MSI) can stimulate angiogenesis in different ways. The vascular endothelial growth factor (VEGF) system is essential for the angiogenetic process and the growth of malignant tumours. The aim of this study was to analyse the relationship between serum VEGF-A and the MSI status of patients with colorectal cancer (CRC).


METHODS
In the study, 249 patients with CRC were divided into a test cohort of 83 patients and a validation cohort of 166. MSI was determined using immunohistochemistry. Tumours lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as high MSI. The rest were considered to be microsatellite stable (MSS). The serum VEGF-A analyses were performed by ELISA.


RESULTS
The tumours of 15 patients in the test cohort and 27 in the validation cohort were classified as MSI. In the test cohort, patients with an MSI tumour had a significantly higher median serum VEGF-A concentration [617 pg/ml (95% CI 445-863)], compared with patients with an MSS tumour, [317 pg/ml (95% CI 224-386)], P = 0.01. A similar relationship was confirmed in the validation cohort, P = 0.04.


CONCLUSIONS
This study provides some evidence to suggest that patients with an MSI tumour have higher serum VEGF-A levels than patients with an MSS tumour. If further validated, these findings could be of importance when considering the effects of anti-VEGF-A treatment.
Hansen
T F
TF
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Vejle, Denmark. torben.hansen@slb.regionsyddanmark.dk
Jensen
L H
LH
Spindler
K-L G
KL
Lindebjerg
J
J
Brandslund
I
I
Jakobsen
A
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D042461:Vascular Endothelial Growth Factor A; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes