Profiling markers of prognosis in colorectal cancer.

Abstract

PURPOSE:

Colorectal cancer is one of the most common forms of cancer in developed nations and the incidence of this disease is increasing. There is a need to further stratify prognostically distinct groups of colorectal cancer, and the purpose of this study was to identify prognostically significant immunohistochemical marker profiles in colorectal cancer.

EXPERIMENTAL DESIGN:

In this study, a range (n = 23) of markers [pRb, p16, p21, p27, p53, proliferating cell nuclear antigen, cyclin D1, bcl-2, epidermal growth factor receptor, C-erb-B2, topoisomerase-I, liver fatty acid-binding protein, matrix metalloproteinases (MMP) 1-3, 7, 9, and 13, MT1-MMP, MT2-MMP, and tissue inhibitors of MMP 1-3] of putative prognostic significance have been investigated by immunohistochemistry on formalin-fixed, wax-embedded sections in a series (n = 90) of stage III (Dukes C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and, where relevant, the proportion of immunoreactive cells was established for each marker.

RESULTS:

Unsupervised two-dimensional hierarchical cluster analysis identified three distinct cluster groups (designated groups 1-3) with different marker profiles. There were significant survival differences between groups 1 and 2 (log rank = 11.48; P = 0.0007) and between groups 1 and 3 (log rank = 8.32; P = 0.0039). Multivariate analysis showed that the complete marker profile was independently the most significant prognostic factor (hazard ratio, 2.27; 95% confidence interval, 1.15-4.48; P = 0.004).

CONCLUSIONS:

This study has identified an immunohistochemical marker profile of colorectal cancer and showed that it is an independent indicator of prognosis in this type of cancer.

• Authors: Matthew S Lyall, Sinclair R Dundas, Stephanie Curran, Graeme I Murray
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 4 Pg. 1184-91 (Feb 15 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16489072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• Fatty Acid-Binding Proteins
• Proliferating Cell Nuclear Antigen
• ErbB Receptors
• DNA Topoisomerases, Type I

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis)
• Cell Cycle Proteins (analysis)
• Cluster Analysis
• Colorectal Neoplasms (metabolism, pathology)
• DNA Topoisomerases, Type I (analysis)
• ErbB Receptors (analysis)
• Fatty Acid-Binding Proteins (analysis)
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Prognosis
• Proliferating Cell Nuclear Antigen (analysis)
• Survival Analysis