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