Profiling markers of prognosis in colorectal cancer

M. S. Lyall, S. R. Dundas, S. Curran, Graeme Ian Murray

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1184-1191
Number of pages7
JournalClinical Cancer Research
Volume12
DOIs
Publication statusPublished - 2006

Keywords

  • CELL NUCLEAR ANTIGEN
  • POOR-PROGNOSIS
  • COLON-CANCER
  • P53 OVEREXPRESSION
  • MATRIX METALLOPROTEINASES
  • THYMIDYLATE SYNTHASE
  • PROTEIN EXPRESSION
  • MOLECULAR MARKERS
  • TUMOR-MARKERS
  • DUKES STAGE

Cite this

Profiling markers of prognosis in colorectal cancer. / Lyall, M. S.; Dundas, S. R.; Curran, S.; Murray, Graeme Ian.

In: Clinical Cancer Research, Vol. 12, 2006, p. 1184-1191.

Research output: Contribution to journalArticle

Lyall, M. S. ; Dundas, S. R. ; Curran, S. ; Murray, Graeme Ian. / Profiling markers of prognosis in colorectal cancer. In: Clinical Cancer Research. 2006 ; Vol. 12. pp. 1184-1191.
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T1 - Profiling markers of prognosis in colorectal cancer

AU - Lyall, M. S.

AU - Dundas, S. R.

AU - Curran, S.

AU - Murray, Graeme Ian

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N2 - 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.

AB - 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.

KW - CELL NUCLEAR ANTIGEN

KW - POOR-PROGNOSIS

KW - COLON-CANCER

KW - P53 OVEREXPRESSION

KW - MATRIX METALLOPROTEINASES

KW - THYMIDYLATE SYNTHASE

KW - PROTEIN EXPRESSION

KW - MOLECULAR MARKERS

KW - TUMOR-MARKERS

KW - DUKES STAGE

U2 - 10.1158/1078-0432.CCR-05-1864

DO - 10.1158/1078-0432.CCR-05-1864

M3 - Article

VL - 12

SP - 1184

EP - 1191

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

ER -