Association of resistance-related protein expression with poor vascularization and low levels of oxygen in human rectal cancer.
Rectal carcinomas of previously untreated patients were analyzed for oxygen status using a computerized polarographic needle electrode histograph. Microvessel density and expression of c-jun, vascular endothelial growth factor (VEGF) and several resistance-related proteins (glutathione S-transferase-pi, GST; thymidylate synthase, TS; metallothioneine, MT) were determined using immunohistochemistry. To examine whether a relationship exists between intratumoral vessel density and tumor oxygenation, microvessel counts were determined in a 400x field using factor-VIII-related antigen and were correlated with the corresponding pO2 values. Linear regression analysis revealed a significant relationship between vessel density and oxygenation status of the tumors. Expression of c-jun, VEGF and resistance-related proteins was correlated with microvessel counts and pO2 values. Significantly lower vessel counts were found in GST- and MT-positive tumors and in tumors with overexpression of c-jun and VEGF than in negative tumors. In addition, significantly lower pO2 values were found in c-jun- and VEGF-positive tumors as well as a tendency for pO2 values to be lower in tumors where MT, GST and TS were expressed. These data show that expression of c-jun, VEGF, and resistance-related proteins is linked with poor vascularization and low oxygenation status in rectal cancer.
Mattern
J
J
German Cancer Research Center, Heidelberg, Germany.
Kallinowski
F
F
Herfarth
C
C
Volm
M
M
D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008668:Metallothionein / Q000032:analysis*; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D013940:Thymidylate Synthase / Q000032:analysis*
D008668:Metallothionein; D013940:Thymidylate Synthase; D005982:Glutathione Transferase; D010100:Oxygen