Predictive molecular markers for colorectal cancer patients with resected liver metastasis and adjuvant chemotherapy Journal Article
| Authors: | Lassmann, S.; Tang, L.; Capanu, M.; Brabletz, T.; Schöpflin, A.; Zur Hausen, A.; Gonen, M.; Kemeny, N.; Shia, J.; Klimstra, D.; Werner, M. |
| Article Title: | Predictive molecular markers for colorectal cancer patients with resected liver metastasis and adjuvant chemotherapy |
| Abstract: | Background & Aims: The aims of the study were to evaluate the predictive value of 8 candidate molecular markers for colorectal cancer (CRC) patients receiving hepatic arterial infusion (floxuridine [FUDR] and dexamethasone) and systemic irinotecan (CPT11) post resection of liver metastasis. Methods: RNA was extracted from microdissected tumor cells of fixed and embedded specimens of resected liver metastases (94 cases) and analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) for thymidine phosphorylase, dihydropyrimidine dehydrogenase, thymidylate synthase, uridine phosphorylase, uridine/cytidine (monophospho)kinase, Bcl-2 related protein, Cyclin-D1, and Survivin expression. Uni- and multivariate statistical analyses and an explorative hierarchical clustering analysis of quantitative RT-PCR data were performed for overall survival and recurrent disease. Results: After adjustment for multiple clinicopathologic parameters, none of the markers were significantly associated with overall survival (except, marginally, Cyclin-D1; P = .06) or extrahepatic recurrence. However, high Survivin (P = .03) and Cyclin-D1 (P = .05) levels were predictive for hepatic recurrence. Hierarchical cluster analysis identified 7 of 94 patients associated with lower hepatic recurrence (P < .001). This patient group was characterized by low Cyclin-D1 and Survivin messenger RNA levels, both genes also clustering together. Conclusions: Cyclin-D1 and Survivin messenger RNA analyzed by standardized, quantitative RT-PCR are predictive markers for CRC patients receiving hepatic arterial infusion (FUDR/dexamethasone) and systemic CPT11 post resection of liver metastasis. Moreover, our exploratory hierarchical cluster analysis of quantitative RT-PCR data supports its potential as an application to define clinically relevant patient subgroups. © 2007 AGA Institute. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; human tissue; aged; aged, 80 and over; middle aged; cancer surgery; major clinical study; overall survival; clinical trial; histopathology; cancer recurrence; postoperative period; fluorouracil; antineoplastic agents; liver neoplasms; adjuvant therapy; cancer patient; cancer diagnosis; colorectal cancer; reverse transcription polymerase chain reaction; tumor markers, biological; dexamethasone; survivin; cancer therapy; irinotecan; colorectal neoplasms; molecular marker; liver metastasis; statistical analysis; messenger rna; adjuvant chemotherapy; tumor cell; predictive value of tests; infusions, intra-arterial; liver surgery; multivariate analysis; cyclin d1; thymidylate synthase; floxuridine; thymidine phosphorylase; uridine phosphorylase; uridine; microdissection; cytidine; dihydropyrimidine dehydrogenase |
| Journal Title: | Gastroenterology |
| Volume: | 133 |
| Issue: | 6 |
| ISSN: | 0016-5085 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2007-12-01 |
| Start Page: | 1831 |
| End Page: | 1839 |
| Language: | English |
| DOI: | 10.1053/j.gastro.2007.08.075 |
| PUBMED: | 18054556 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: GASTA" - "Source: Scopus" |
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