Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases Journal Article
| Authors: | Maithel, S. K.; Gonen, M.; Ito, H.; DeMatteo, R. P.; Allen, P. J.; Fong, Y.; Blumgart, L. H.; Jarnagin, W. R.; D'Angelica, M. I. |
| Article Title: | Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases |
| Abstract: | Background: The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known. Methods: Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection. Results: One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P <.0001] and 50% vs 80% [P <.0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P =.03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P =.03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs15 months [P =.03] and 48% vs 82% [P =.001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis. Conclusion: In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker. © 2012 Mosby, Inc. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; controlled study; human tissue; protein expression; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; cancer surgery; survival rate; retrospective studies; unclassified drug; major clinical study; dna-binding proteins; disease course; liver neoplasms; disease free survival; postoperative care; combined modality therapy; outcome assessment; follow up; follow-up studies; prospective studies; colorectal cancer; tumor markers, biological; excision repair cross complementing protein 1; cancer resistance; colorectal neoplasms; tissue section; scatter factor; rna; liver metastasis; gene expression regulation, neoplastic; quantitative analysis; liver resection; hepatectomy; real time polymerase chain reaction; preoperative treatment; drug therapy; thymidylate synthase; rna extraction; dna topoisomerase; scatter factor receptor; recurrence free survival; proto-oncogene proteins c-met; nucleic acid binding protein; xeroderma pigmentosum group g protein; endonucleases; hepatocyte growth factor; cancer prognosis; xeroderma pigmentosum group a protein |
| Journal Title: | Surgery |
| Volume: | 151 |
| Issue: | 2 |
| ISSN: | 0039-6060 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2012-02-01 |
| Start Page: | 162 |
| End Page: | 170 |
| Language: | English |
| DOI: | 10.1016/j.surg.2011.07.020 |
| PROVIDER: | scopus |
| PUBMED: | 21982065 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: SURGA" - "Source: Scopus" |
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