Profiling markers of prognosis in colorectal cancer.
OBJECTIVE
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.


METHODS
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.
Lyall
Matthew S
MS
Department of Pathology, University of Aberdeen, Aberdeen, UK.
Dundas
Sinclair R
SR
Curran
Stephanie
S
Murray
Graeme I
GI
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins / Q000032:analysis; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004264:DNA Topoisomerases, Type I / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D050556:Fatty Acid-Binding Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050556:Fatty Acid-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D066246:ErbB Receptors; D004264:DNA Topoisomerases, Type I