Correlations between cyclooxygenase-2 expression and angiogenic factors in primary tumors and liver metastases in colorectal cancer.
BACKGROUND
Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer.


METHODS
Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD.


RESULTS
The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P = 0.005, rs = 0.428), VEGF-A (P = 0.039, rs = 0.314), TP (P = 0.005, rs = 0.422) and MVD (P = 0.046, rs = 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P = 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P = 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P = 0.247; P = 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P = 0.033) as well as in primary tumors (P = 0.008).


CONCLUSIONS
The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstrated here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.
Nakamoto
Regina Hiromi
RH
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Uetake
Hiroyuki
H
Iida
Satoru
S
Kolev
Yanislav Velchev
YV
Soumaoro
Labile Togba
LT
Takagi
Yoko
Y
Yasuno
Masamichi
M
Sugihara
Kenichi
K
D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply* / Q000737:chemistry* / Q000201:enzymology / Q000556:secondary; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D013939:Thymidine Phosphorylase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; D013939:Thymidine Phosphorylase