Thymidylate synthase expression in hepatic tumors is a predictor of survival and progression in patients with resectable metastatic colorectal cancer Journal Article
| Authors: | Gonen, M.; Hummer, A.; Zervoudakis, A.; Sullivan, D.; Fong, Y.; Banerjee, D.; Klimstra, D.; Cordon-Cardo, C.; Bertino, J.; Kemeny, N. |
| Article Title: | Thymidylate synthase expression in hepatic tumors is a predictor of survival and progression in patients with resectable metastatic colorectal cancer |
| Abstract: | Purpose: To investigate the role of thymidylate synthase (TS), p53, and epidermal growth factor receptor (EGF-R) expressions in hepatic tumors in predicting overall survival (OS), progression-free survival (PFS), and hepatic progression-free survival (HPFS) in patients with resectable metastatic colorectal cancer who were randomly assigned to receive either systemic chemotherapy (SYS) alone or systemic and hepatic arterial infusion (HAI+SYS) chemotherapy following liver surgery. Patients and Methods: Tissues from metastatic tumors were collected during liver resection from 156 patients, and marker expressions were determined using immunohistochemistry on frozen samples. Univariate associations between marker expressions and baseline variables with OS, PFS, and HPFS were examined. Independent predictors of outcome were determined using a multivariate Cox model. Results: In multivariate analyses, TS overexpression was found to be an independent factor of poor prognosis in OS (P < .01), PFS (P = .06), and HPFS (P < .01). In addition, resection margin was a significant independent factor for all three outcomes. Patients who received HAI+SYS experienced delayed progression in general, and in the liver, specifically. Increased levels of serum alkaline phosphatase correlated with hepatic progression. We also found a significant TS-treatment interaction for OS (P = .01) in multivariate analysis. In particular, TS+ patients receiving HAI+SYS had significantly higher survival than those receiving SYS (64 months v 21 months; P = .01). Conclusion: TS levels in hepatic tumors and resection margin are independent predictors of survival and progression in patients with metastatic colorectal cancer, whereas p53 and EGFR are not independent predictors. Treatment with HAI+SYS significantly improved the survival profile of TS+ patients. © 2003 by American Society of Clinical Oncology. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; protein expression; aged; disease-free survival; middle aged; major clinical study; overall survival; genetics; clinical trial; disease course; histopathology; cancer growth; liver neoplasms; cancer adjuvant therapy; disease free survival; postoperative care; antineoplastic agent; colorectal cancer; metastasis; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor; receptor, epidermal growth factor; pathology; protein p53; colorectal neoplasms; alkaline phosphatase; liver metastasis; biosynthesis; disease progression; colorectal tumor; liver tumor; prediction and forecasting; predictive value of tests; intraarterial drug administration; infusions, intra-arterial; tumor suppressor protein p53; alkaline phosphatase blood level; thymidylate synthase; genetic marker; hepatic artery; genetic markers; humans; prognosis; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 21 |
| Issue: | 3 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2003-02-01 |
| Start Page: | 406 |
| End Page: | 412 |
| Language: | English |
| DOI: | 10.1200/jco.2003.06.060 |
| PUBMED: | 12560427 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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MSK Authors
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60Hummer -
136
Banerjee -
1030Gonen -
363Bertino -
612
Cordon-Cardo -
978Klimstra -
775Fong -
544Kemeny -
4
Sullivan -
32Zervoudakis
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