Messenger RNA expression of vascular endothelial growth factor and its receptors in primary colorectal cancer and corresponding liver metastasis.
BACKGROUND
Antiangiogenic therapies have been developed recently in combination with traditional chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to clarify the association between messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and its receptors (VEGFR) in primary colorectal cancer and those in corresponding liver metastasis.


METHODS
Thirty-one paired formalin-fixed, paraffin-embedded tumor tissues of colorectal cancer and liver metastasis were dissected by laser capture microdissection. After the mRNA was isolated, a quantitative fluorescent dye real-time reverse transcription-polymerase chain reaction system was used for gene expression measurement.


RESULTS
There was a positive correlation between VEGF mRNA levels in primary colorectal cancer and those in matched liver metastasis (P = .0083, r (s) = 0.48). However, there was no association between mRNA levels of VEGFRs in primary tumor and those in liver metastasis. The mRNA levels of VEGF were associated with those of VEGFR-1 (P = .0026, r (s) = 0.39) but not with those of VEGFR-2. The mRNA levels of VEGF were higher than that of either of the VEGFRs (P < .0001).


CONCLUSIONS
We can predict VEGF mRNA levels, but not those of VEGFRs, in liver metastasis by measuring those in primary colorectal cancer. The mRNA expression of VEGFRs may be more dependent on the surrounding environment than that of VEGF. These results should be useful for the formulation of antiangiogenic therapies for metastatic colorectal cancer. Further studies will be necessary to validate these preliminary data.
Kobayashi
Hirotoshi
H
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. h-kobayashi.srg2@tmd.ac.jp
Sugihara
Kenichi
K
Uetake
Hiroyuki
H
Higuchi
Tetsuro
T
Yasuno
Masamichi
M
Enomoto
Masayuki
M
Kuramochi
Hidekazu
H
Lenz
Heinz-Josef
HJ
Danenberg
Kathleen D
KD
Danenberg
Peter V
PV
D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1