title: Importance of thymidine phosphorylase expression in tumor stroma as a prognostic factor in patients with advanced colorectal carcinoma.
abstract: Thymidine phosphorylase (TP) is a unique enzyme involved not only in angiogenesis, but in 5-fluorouracil (5-FU) metabolism as well. TP is produced by both tumor and stromal cells. The aim of this study was to reveal the clinical implication of TP localization in tumor tissues. Advanced colorectal cancer specimens (n=97) were prepared for immunohistochemical staining using monoclonal antibodies against TP, p53, vascular endothelial growth factor (VEGF), factor VIII, CD68 and thymidylate synthase (TS). Clinicopathological factors and the clinical prognosis were examined for each indicator. High tumor TP expression and high stromal TP expression were observed in 38% (36/95 cases) and 49% (47/95 cases) of the cases, respectively. High tumor TP expression tended to correlate with microvessel density (MVD) (p=0.0511). Among patients who underwent curative resection, those with high stromal TP expression had a favorable prognosis (p=0.0127). High stromal TP status was also a strong prognostic factor in the group receiving adjuvant 5-FU derivatives (p=0.0222). TP produced by tumor cells has a stimulatory effect on tumor angiogenesis, while that produced by stromal cells plays an entirely different role. The latter may enhance the anticancer effect of 5-FU via its catalyzed function.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyou-ku, Tokyo 113-8519, Japan. yasuno.srg2@tmd.ac.jp
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yasuno
authors.forename: Takeo
authors.initials: T
authors.lastname: Mori
authors.forename: Morio
authors.initials: M
authors.lastname: Koike
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Toichiro
authors.initials: T
authors.lastname: Takizawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shimizu
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011446:Prospective Studies; D017154:Stromal Cells; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D013939:Thymidine Phosphorylase; D005472:Fluorouracil