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

被引:175
作者
Aschele, C
Debernardis, D
Casazza, S
Antonelli, G
Tunesi, G
Baldo, C
Lionetto, R
Maley, F
Sobrero, A
机构
[1] Ist Nazl Ricerca Cancro, Dept Med Oncol, Genoa, Italy
[2] EO Ospedali Galliera, Dept Pathol, Genoa, Italy
[3] Univ Udine, I-33100 Udine, Italy
[4] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA
关键词
D O I
10.1200/JCO.1999.17.6.1760
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
purpose: To determine whether immunohistochemical thymidylate synthase(TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer heated 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 find all the parameters of clinical outcome analyzed. In patients whose 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 races 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 ta TS inhibitors who may be candidates for alternative chemotherapy regimens. (C) 1999 by American Society of Clinical Oncology.
引用
收藏
页码:1760 / 1770
页数:11
相关论文
共 56 条
  • [1] ARDALAN B, 1980, CANCER RES, V40, P1431
  • [2] ASCHELE C, 1992, CANCER RES, V52, P1855
  • [3] Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a multicentric phase II study
    Aschele, C
    Guglielmi, A
    Frassineti, GL
    Milandri, C
    Amadori, D
    Labianca, R
    Vinci, M
    Tixi, L
    Caroti, C
    Ciferri, E
    Verdi, E
    Rosso, R
    Sobrero, A
    [J]. BRITISH JOURNAL OF CANCER, 1998, 77 (02) : 341 - 346
  • [4] p53 nuclear protein overexpression in colorectal cancer: A dominant predictor of survival in patients with advanced hepatic metastases
    Belluco, C
    Guillem, JG
    Kemeny, N
    Huang, Y
    Klimstra, D
    Berger, MF
    Cohen, AM
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (10) : 2696 - 2701
  • [5] Benhattar J, 1996, INT J CANCER, V69, P190, DOI 10.1002/(SICI)1097-0215(19960621)69:3<190::AID-IJC7>3.0.CO
  • [6] 2-V
  • [7] BERGER SH, 1985, MOL PHARMACOL, V28, P461
  • [8] Colorectal cancer - Is there an alternative to 5-FU?
    Bleiberg, H
    [J]. EUROPEAN JOURNAL OF CANCER, 1997, 33 (04) : 536 - 541
  • [9] Modulation of high-dose infusional fluorouracil by low-dose methotrexate in patients with advanced or metastatic colorectal cancer: Final results of a randomized European Organization for Research and Treatment of Cancer Study
    Blijham, G
    Wagener, T
    Wils, J
    deGreve, J
    Buset, M
    Bleiberg, H
    Lacave, A
    Dalmark, M
    Selleslag, J
    Collette, L
    Sahmoud, T
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (08) : 2266 - 2273
  • [10] CAROTI C, 1998, P 8 INT C ANT TREAT, P96