Use of Localization and Activity of Thymidine Phosphorylase in Human Gynecological Tumors for Predicting Sensitivity to Pyrimidine Antimetabolite Therapy: An Observational StudyYuzuru Kotake1*, Toru Sasaki2, Hiroshi Sasaki1, Minoru Akiyama9, Kazunori Ochiai1, Shinji Sato3, Akira Yajima4, Kazuo Hasegawa5, Michiaki Yakushiji6, Shinichi Tsuchiya7 and Kiichiro Noda8
- *Corresponding Author:
- Dr. Yuzuru Kotake
Department of Obstetrics and Gynecology
Jikei Kashiwa Hospital, 163-1 Kashiwashita
Kashiwa-shi, Chiba 277-8567, Japan
E-mail: [email protected]
Received: March 25, 2011; Accepted date: August 09, 2011; Published: August 12, 2011
Citation: Kotake Y, Sasaki T, Sasaki H, Akiyama M, Ochiai K, et al. (2011) Use of Localization and Activity of Thymidine Phosphorylase in Human Gynecological Tumors for Predicting Sensitivity to Pyrimidine Antimetabolite Therapy: An Observational Study. J Cytol Histol 2:121. doi:10.4172/2157-7099.1000121
Copyright: © 2011 Kotake Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme in the conversion of 5 ′ -deoxy- 5-fluorouridine (5 ′ -dFUrd), an intermediate metabolite of capecitabine (Xeloda ® ), to 5-fluorouracil (5-FU). We investigated the correlation between dThdPase activity and immunohistochemical staining in gynecological carcinoma and adjacent normal tissues. We hypothesize that the differential dThdPase activity between tumors and adjacent tissue is predictive of response to treatment with pyrimidine antimetabolites.
Methods: In 45 samples of carcinoma tissue and 35 of adjacent normal tissue from 45 patients, we measured dThdPase activity as well as immunoreactivity using an anti-dThdPase monoclonal antibody and macrophage and histiocyte-specific antibodies.
Results: dThdPase activity in tumor tissue was significantly higher than that in the corresponding adjacent normal tissue in all samples tested (12 uterine cervical, 19 endometrial, and 4 ovarian tumors). Anti-dThdPase immunopositivity was observed in the epithelial tumor cells of 76.9% of uterine cervical cancer samples, 60.0% of endometrial cancer samples and 63.6% of ovarian cancer samples. In stromal tissue, 84.6% of uterine cervical tumors (11/13), 90.0% of endometrial tumors (18/20), and 81.8% of ovarian tumors (9/11) were immunopositive for anti-dThdPase in interstitial cells (mainly macrophages). Macrophages were also strongly reactive in the stromal tissues of uterine cervical, endometrial, and ovarian cancers. The correlation between dThdPase activity and intensity of immunohistochemical staining of epithelial tumor cells with anti-dThdPase monoclonal antibody was statistically significant in endometrial carcinoma ( P = 0.008) but borderline in uterine cervical tumors ( P = 0.077). We found a good correlation between dThdPase activity and staining of epithelial tumor cells, particularly in the case of endometrial cancer.
Conclusions: We show that gynecological carcinomas show increased dThdPase activity, and this activity correlates with dThdPase staining of tumor epithelial cells. Thus, dThdPase staining of biopsy specimens could be useful in predicting the outcome of therapy with pyrimidine metabolites.