title: Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy.
abstract: Thymidine phosphorylase (TP) is structurally similar to platelet-derived endothelial cell growth factor, and it activates 5-fluorouracil (5-FU) prodrugs and also promotes angiogenesis. In the present study, the possibility of using TP expression as a biomarker for 5-FU prodrugs, and the significance of TP as an angiogenic factor, were investigated in patients with gynecological tumors. The subjects enrolled in the study were 188 patients with gynecological tumors who provided informed consent and underwent tumor resection at the Department of Obstetrics and Gynecology of Tokai University Hospital between February 2002 and January 2010. Measurement of the enzymatic activity of TP and dihydropyrimidine dehydrogenase (DPD) was performed by enzyme-linked immunosorbent assay. In addition, immunohistochemistry (IHC) analysis of microvessels by monochrome imaging, western blotting and reverse transcription-polymerase chain reaction were performed. The mean TP activity and the TP/DPD ratio were increased in squamous cell carcinoma of the cervix (306.9 and 2.2 U/mg protein, respectively) and adenosquamous carcinoma (317.6 and 1.4 U/mg protein, respectively) compared with benign tumors and other malignancies, including endometrial (uterine) carcinoma, ovarian serous adenocarcinoma and ovarian mucinous adenocarcinoma. However, these parameters were also elevated in other histological types of cancer such as clear cell adenocarcinoma of the ovary (115.2 and 2.1 U/mg protein, respectively), in which the microvessel area was the largest of all the histological types analyzed. Since high TP expression and a high TP/DPD ratio were identified in other tumors besides cervical cancer, it is possible that patients for whom 5-FU prodrugs are indicated could be selected appropriately if their TP activity is determined and their TP expression is analyzed by IHC prior to initiation of the treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Shida
authors.affiliation: Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazawa
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiwara
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirasawa
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Pathology, Tokai University Oiso Hospital, Oiso, Kanagawa 259-0198, Japan.
authors.forename: Naruaki
authors.initials: N
authors.lastname: Matsui
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University Hachioji Hospital, Hachioji, Tokyo 192-0032, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Muramatsu
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Mikami
keywords: 5-FU prodrug; dihydropyrimidine dehydrogenase; gynecological tumor; thymidine phosphorylase