Microvessel density and the association with single nucleotide polymorphisms of the vascular endothelial growth factor receptor 2 in patients with colorectal cancer.
The measurement of microvessel density (MVD) is a widely accepted method for assessing the neoangiogenetic activity in neoplasia. The aim of the present study was to compare MVD with single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 genes and, furthermore, with quantitative measurements of the receptors in colorectal cancer (CRC) tissue. Prognosis was also assessed. Blood and tissue were collected from 110 patients surgically resected for CRC. SNPs were analysed from genomic DNA by polymerase chain reaction. MVD was assessed by immunohistochemistry using CD34 and CD105 combined with caldesmon in order to identify also immature vessels. Microvessels were counted in three fields of vision, and the mean MVD was used for statistical analysis. The VEGFR-2 1192 C/T and -604 T/C SNPs were associated with the MVD assessed by CD105. The median MVD score for the 1192 CC genotype was significantly lower compared to the CT + TT genotypes (p = 0.002). The median MVD score for the -604 CC genotype was significantly higher compared to the TT + TC genotypes (p = 0.009). A possible association, although non-significant, was demonstrated for the CD34-positive microvessels. The 1192 CC genotype and the -604 TT + TC genotypes correlated with improved survival. This is the first report on correlations between SNPs in the VEGF receptor genes and MVD in patients with CRC. Associations were shown between two SNPs in the VEGFR-2 gene and the CD105-positive microvessels indicating an impact on neoangiogenesis. Moreover, an association between the SNPs and survival was demonstrated. The clinical implications of these findings need further investigations.
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Kabbeltoft 25, 7100, Vejle, Denmark. torben.hansen@slb.regionsyddanmark.dk
Torben Frøstrup
TF
Hansen
Flemming Brandt
FB
Sørensen
Karen-Lise Garm
KL
Spindler
Dorte Aalund
DA
Olsen
Rikke Fredslund
RF
Andersen
Jan
J
Lindebjerg
Ivan
I
Brandslund
Anders
A
Jakobsen
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000401:mortality; D000071063:Endoglin; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels / Q000033:anatomy & histology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012189:Retrospective Studies; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D040301:Vascular Endothelial Growth Factor Receptor-2