TY - JOUR
T1 - Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil- based chemotherapy
AU - Aschele, Carlo
AU - Debernardis, Domizia
AU - Casazza, Stefania
AU - Antonelli, Giovanna
AU - Tunesi, Gianni
AU - Baldo, Chiara
AU - Lionetto, Rita
AU - Maley, Frank
AU - Sobrero, Alberto
PY - 1999
Y1 - 1999
N2 - Purpose: To determine whether immunohistochemical thymidylate synthase (TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer treated by fluorouracil (FUra)-based chemotherapy. Patients and Methods: TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 48 patients homogenously treated by bolus FUra plus methotrexate alternating with continuous-infusion FUra plus leucovorin. These measurements were retrospectively correlated with patient characteristics and clinical outcome. Results: A significant correlation was found between intratumoral TS expression and all the parameters of clinical outcome analyzed. In patients whoso 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 shrinkage after chemotherapy was linearly related to TS immunoreactivity (r = .56, P = .00004), and its mean values were 65% and 14% with low and high TS levels, respectively (P = .0001). By logistic regression analysis, low TS expression was the single best predictor of response to chemotherapy (relative probability, 5.0). In patients with low and high TS expression, the median time to progression was 9.6 months v 6.2 months (P = .005) and the median survival time 18.4 months v 15.4 months (P = .02), respectively. Two- and 3- year survival rates were 41% v 15% and 19% v 0% (P = .02), respectively. Conclusion: in this cohort of homogenously treated patients, intratumor TS content was a major predictor of clinical outcome. Immunohistochemical TS quantitation provides a convenient, low-cost technique for identifying patients unresponsive to TS inhibitors who may be candidates for alternative chemotherapy regimens.
AB - Purpose: To determine whether immunohistochemical thymidylate synthase (TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer treated by fluorouracil (FUra)-based chemotherapy. Patients and Methods: TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 48 patients homogenously treated by bolus FUra plus methotrexate alternating with continuous-infusion FUra plus leucovorin. These measurements were retrospectively correlated with patient characteristics and clinical outcome. Results: A significant correlation was found between intratumoral TS expression and all the parameters of clinical outcome analyzed. In patients whoso 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 shrinkage after chemotherapy was linearly related to TS immunoreactivity (r = .56, P = .00004), and its mean values were 65% and 14% with low and high TS levels, respectively (P = .0001). By logistic regression analysis, low TS expression was the single best predictor of response to chemotherapy (relative probability, 5.0). In patients with low and high TS expression, the median time to progression was 9.6 months v 6.2 months (P = .005) and the median survival time 18.4 months v 15.4 months (P = .02), respectively. Two- and 3- year survival rates were 41% v 15% and 19% v 0% (P = .02), respectively. Conclusion: in this cohort of homogenously treated patients, intratumor TS content was a major predictor of clinical outcome. Immunohistochemical TS quantitation provides a convenient, low-cost technique for identifying patients unresponsive to TS inhibitors who may be candidates for alternative chemotherapy regimens.
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M3 - Article
C2 - 10561213
AN - SCOPUS:0032997572
VL - 17
SP - 1760
EP - 1770
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 6
ER -