Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy

Citation
C. Aschele et al., Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy, J CL ONCOL, 17(6), 1999, pp. 1760-1770
Citations number
53
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
JOURNAL OF CLINICAL ONCOLOGY
ISSN journal
0732183X → ACNP
Volume
17
Issue
6
Year of publication
1999
Pages
1760 - 1770
Database
ISI
SICI code
0732-183X(199906)17:6<1760:IQOTSE>2.0.ZU;2-0
Abstract
purpose: To determine whether immunohistochemical thymidylate synthase(TS) quantitation predicts for clinical outcome in patients with advanced colore ctal cancer heated by fluorouracil (FUra)-based chemotherapy. Patients and Methods: TS levels were measured immunohistochemically on arch ival specimens of colorectal cancer metastases from 48 patients homogenousl y treated by bolus FUra plus methotrexate alternating with continuous-infus ion FUra plus leucovorin. These measurements were retrospectively correlate d with patient characteristics and clinical outcome. Results: A significant correlation was found between intratumoral TS expres sion find all the parameters of clinical outcome analyzed. In patients whos e tumors had low (n = 27) and high (n =21) TS levels, the overall response rates were 67% and 24%, respectively (P = .003). The percentage of tumor sh rinkage after chemotherapy was linearly related to TS immunoreactivity (r = .56, P = .00004), and its mean values were 65% and 14% with low and high T S levels, respectively (P = .0001). By logistic regression analysis, low TS expression was the single best predictor of response to chemotherapy (rela tive probability, 5.0), In patients with low and high TS expression, the me dian time to progression was 9.6 months v 6.2 months (P = .005) and the med ian survival time 18.4 months v 15.4 months (P = .02), respectively. Two- a nd 3-year survival races were 41% v 15% and 19% v 0% (P = .02), respectivel y Conclusion: In this cohort of homogenously treated patients, intratumor TS content was a major predictor of clinical outcome. Immunohistochemical TS q uantitation provides a convenient, low-cost technique for identifying patie nts unresponsive ta TS inhibitors who may be candidates for alternative che motherapy regimens. (C) 1999 by American Society of Clinical Oncology.