Prognostic significance of serum thymidine phosphorylase concentration in esophageal squamous cell carcinoma.
BACKGROUND
Thymidine phosphorylase (dThdPase), which also is referred to as platelet-derived endothelial cell growth factor, is a potent inducer of angiogenesis in malignant tumors. Increased dThdPase expression and activity have been found to be associated with poor prognosis in various solid tumor tissues. Because very little was known about the significance of serum dThdPase concentration (S-dThdPase), the objective of this study was to analyze the clinicopathologic significance of S-dThdPase in the patients with esophageal squamous cell carcinoma.


METHODS
The S-dThdPase was measured by enzyme-linked immunosorbent assay in 77 healthy controls and 153 patients with primary esophageal squamous cell carcinoma. A total of 80 patients underwent surgery alone; 46 patients received chemoradiotherapy alone; 17 patients received chemoradiotherapy followed by surgery; and 10 patients did not receive any treatment. Thymidine phosphorylase expression in esophageal carcinoma tissues was examined by immunohistochemistry. The clinicopathologic value and prognostic value of S-dThdPase was determined in 80 patients treated by surgery alone.


RESULTS
The S-dThdPase is significantly higher in patients with esophageal carcinoma than in healthy controls (30.8 +/- 31.8 ng/mL vs. 13.8 +/- 7.6 ng/mL; P < 0.001). Statistically significant differences in S-dThdPases were observed depending on tumor size (P < 0.01) and tumor depth (P < 0.01). A S-dThdPase of more than 29.0 ng/mL (which represented the mean plus 2 standard deviation of the concentration in healthy controls) was associated with dThdPase expression (P = 0.022), poor response (P = 0.022), and poor survival (P < 0.01). Because S-dThdPase was associated with tumor depth, S-dThdPase was not an independent prognostic factor (P = 0.095).


CONCLUSIONS
A high S-dThdPase is associated with depth of tumor invasion and poor response to treatment.
Shimada
Hideaki
H
Department of Academic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Japan, 260-8677. hshimada@srgy201.m.chiba-u.ac.jp
Takeda
Akihiko
A
Shiratori
Tooru
T
Nabeya
Yoshihiro
Y
Okazumi
Shin-ichi
S
Matsubara
Hisahiro
H
Funami
Yutaka
Y
Hayashi
Hideki
H
Gunji
Yoshio
Y
Kobayashi
Susumu
S
Suzuki
Takao
T
Ochiai
Takenori
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000628:therapy; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000628:therapy; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000097:blood*
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D013939:Thymidine Phosphorylase