Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

Abstract

PURPOSE:

Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.

PATIENTS AND METHODS:

A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery.

RESULTS:

The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001).

CONCLUSION:

This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.

• Authors: Richard D Kennedy, Max Bylesjo, Peter Kerr, Timothy Davison, Julie M Black, Elaine W Kay, Robert J Holt, Vitali Proutski, Miika Ahdesmaki, Vadim Farztdinov, Nicolas Goffard, Peter Hey, Fionnuala McDyer, Karl Mulligan, Julie Mussen, Eamonn O'Brien, Gavin Oliver, Steven M Walker, Jude M Mulligan, Claire Wilson, Andreas Winter, Diarmuid O'Donoghue, Hugh Mulcahy, Jacintha O'Sullivan, Kieran Sheahan, John Hyland, Rajiv Dhir, Oliver F Bathe, Ola Winqvist, Upender Manne, Chandrakumar Shanmugam, Sridhar Ramaswamy, Eduardo J Leon, William I Smith Jr, Ultan McDermott, Richard H Wilson, Daniel Longley, John Marshall, Robert Cummins, Daniel J Sargent, Patrick G Johnston, D Paul Harkin
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 35 Pg. 4620-6 (Dec 10 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 22067406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Formaldehyde

Topics

• Aged
• Colonic Neoplasms (genetics, pathology)
• Female
• Formaldehyde
• Gene Expression Profiling
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local (genetics, pathology)
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis (methods)
• Paraffin Embedding (methods, standards)
• Prognosis
• Retrospective Studies
• Risk Factors
• Tissue Fixation