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.

• Authors: Silke Lassmann, Laura Tang, Marinela Capanu, Thomas Brabletz, Anja Schöpflin, Axel Zur Hausen, Mithat Gonen, Nancy Kemeny, Jinru Shia, David Klimstra, Martin Werner
• Journal: Gastroenterology (Gastroenterology) Vol. 133 Issue 6 Pg. 1831-9 (Dec 2007) ISSN: 1528-0012 [Electronic] United States
• PMID: 18054556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage)
• Biomarkers, Tumor (blood)
• Colorectal Neoplasms (blood, drug therapy, pathology, surgery)
• Female
• Humans
• Infusions, Intra-Arterial
• Liver Neoplasms (blood, drug therapy, secondary, surgery)
• Male
• Middle Aged
• Predictive Value of Tests