Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival.
BACKGROUND
Recently, the usefulness of intratumoral microvessel density (IMD) and expression of several angiogenic factors as prognostic indicators have been demonstrated in several human solid tumors.


METHODS
One hundred four patients with pancreatic ductal adenocarcinoma were examined retrospectively. The investigated clinicopathologic and immunohistologic data included staining for vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP), basic fibroblast growth factor (bFGF), CD34 (for calculating IMD), p53, and Ki-67.


RESULTS
Multivariate analysis for both overall and relapse-free survival revealed two independent variables, IMD and TP staining in stromal cells (TPs, P < 0.02). Whereas the frequency of hepatic metastasis was correlated significantly with cytoplasmic expression of TP or bFGF in tumor cells (TPc, bFGFc), IMD, and p53 status, local recurrence was significantly more common in patients with positive staining for TPs, bFGF in stromal cells (bFGFs), and for the pM category (P < 0.05). TPc, bFGFc, VEGF, and p53 expression correlated with IMD (P < 0.01), although TPs and bFGFs expression did not. VEGF and IMD status correlated with p53 expression (P < 0.001), although TP, bFGF, and Ki-67 status did not.


CONCLUSIONS
TPs expression and IMD were revealed to be valuable tools for predicting overall and relapse-free survival in patients with pancreatic adenocarcinoma. Whereas TPc and bFGFc are likely to participate in hepatic metastasis by means of their angiogenic properties, TPs and bFGFs may be related to local tumor progression. Angiogenesis in human pancreatic carcinoma may be dependent on VEGF, TP, and bFGF. p53 abnormality is likely to take part in VEGF-related angiogenesis.
Fujioka
S
S
Department of Surgery 1, University Hospital, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. shuichifujioka@hotmail.com
Yoshida
K
K
Yanagisawa
S
S
Kawakami
M
M
Aoki
T
T
Yamazaki
Y
Y
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D019394:Ki-67 Antigen; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013939:Thymidine Phosphorylase