Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer.
BACKGROUND
We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer. However, little is known about its possible changes in response to radiotherapy (RTX), which is frequently given to rectal tumors as a neoadjuvant treatment to improve the prognosis. We therefore investigated the biologic effects of RTX on these parameters using fresh-frozen biopsy samples of tumor and normal mucosa tissue before and after RTX.


METHODS
Biopsy samples were taken from a total of 34 patients before and after either a short course or long course of RTX combined with chemotherapy. The following parameters were analyzed by immunohistochemistry, flow cytometry, or quantitative real-time polymerase chain reaction: Microvessel density, leukocyte infiltration, proliferating epithelial and tumor cells, proliferating endothelial cells, adhesion molecule expression on endothelial cells, and the angiogenic mRNA profile.


RESULTS
The tumor biopsy samples taken after RTX treatment demonstrated a significant decrease in microvessel density and the number of proliferating tumor cells and proliferating endothelial cells (p < 0.001). In contrast, the leukocyte infiltration, the levels of basic fibroblast growth factor in carcinoma tissue, and the adhesion molecule expression on endothelial cells in normal as well as carcinoma tissue increased significantly (p < 0.05).


CONCLUSIONS
Our data show that together with an overall decrease in tumor cell and endothelial cell proliferation, RTX results in an increase in the expression of adhesion molecules that stimulate leukocyte infiltration. This suggests the possibility that, in addition to its direct cytotoxic effect, radiation may also stimulate an immunologic tumor response that could contribute to the documented improvement in local tumor control and distal failure rate of rectal cancers.
Baeten
Coen I M
CI
Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands. C.Baeten@surgery.azm.nl
Castermans
Karolien
K
Lammering
Guido
G
Hillen
Femke
F
Wouters
Bradly G
BG
Hillen
Harry F P
HF
Griffioen
Arjan W
AW
Baeten
Cornelius G M I
CG
D000368:Aged; D004358:Drug Therapy; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control*; D011878:Radiotherapy; D012004:Rectal Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000628:therapy*