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The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer.
Abstract
PURPOSE: We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS expression. PATIENTS AND METHODS: The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immunohistochemically assessed with the monoclonal antibody TS 106. RESULTS: Forty-nine percent of patients whose tumors had low TS levels (n = 91) were disease free at 5 years compared with 27% of patients with high levels of TS (n = 203; P < .01). Moreover, 60% of patients with low TS levels were alive after 5 years compared with 40% of patients with high TS levels (P < .01). The level of TS protein was significantly associated with Dukes' stage (P < .01); patients with a more advanced Dukes' stage had a significantly higher level of TS. The level of TS expression remained prognostic for both disease-free survival (P < .01) and survival (P < .05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-eight percent and 54% of patients with high TS levels (n = 71) were disease free and alive, respectively, after 5 years when treated with chemotherapy, compared with 17% and 31%, respectively, of similar patients when treated with surgery alone (n = 64) (P < .01). No difference was noted in disease-free survival (P = .46) or survival (P = .43) in patients with low TS levels. CONCLUSION: The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significant improvement in disease-free and overall survival for patients with high TS levels. Prospective studies measuring TS levels will be needed to understand further the role of TS as a prognosticator of survival and chemotherapeutic benefit.
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Cites
Asymptotically Efficient Rank Invariant Test Procedures
Peto, R., & Peto, J. (1972) · Journal of the Royal Statistical Society. Series A (General) · doi:10.2307/2344317 · Cited by 3,393
Cited by
Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism
Peters, G. J., Backus, H. H. J., Freemantle, S., van Triest, B., Codacci-Pisanelli, G., van der Wilt, C. L., Smid, K., Lunec, J., Calvert, A. H., Marsh, S., et al. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(02)00082-0 · Cited by 420
Villafranca, E., Okruzhnov, Y., Dominguez, M. A., García-Foncillas, J., Azinovic, I., Martínez, E., Illarramendi, J. J., Arias, F., Martínez-Monge, R., Salgado, E., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.6.1779 · Cited by 308
Fujii, R., Seshimo, A., & Kameoka, S. (2003) · International Journal of Clinical Oncology · doi:10.1007/s101470300013 · Cited by 82
Metadata
- Authors
- Johnston, P. G., Fisher, E. R., Rockette, H. E., Fisher, B., Wolmark, N., Drake, J. C., Chabner, B. A., & Allegra, C. J.
- Venue
- Journal of Clinical Oncology
- Published
- 1994-12
- Volume
- 12
- Issue
- 12
- Pages
- 2640-2647
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W1884213330
- Cited by
- 405
- References
- 1
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- Johnston, P. G., Fisher, E. R., Rockette, H. E., Fisher, B., Wolmark, N., Drake, J. C., Chabner, B. A., & Allegra, C. J. (1994). The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.1994.12.12.2640
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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