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Immunohistochemical Expressions of Ki-67, Cyclin D1, ß-Catenin, Cyclooxygenase-2, and Epidermal Growth Factor Receptor in Human Colorectal Adenoma: A Validation Study of Tissue Microarrays

¹ Division of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt-Ingram Cancer Center and Vanderbilt Epidemiology Center, ² Division of Gastroenterology, Hepatology, and Nutrition, Departments of Medicine and ³ Pathology, Vanderbilt University Medical Center, Nashville, Tennessee

Requests for reprints: Wei Zheng, Vanderbilt University Medical Center, S-1121A Medical Center North, Nashville, TN 37232-2587. Phone: 615-936-0682; Fax: 615-322-1754. E-mail: wei.zheng{at}vanderbilt.edu

Background: Tissue microarray (TMA) holds promise as a high-throughput method for the analysis of biomarkers in tissue specimens. The validity and reliability of this method, however, may vary for different biomarkers in different tissue specimens.

Objectives: In this study, we evaluated the validity and reliability of using TMA to assess biomarkers in colorectal adenomas.

Methods: Sixty-three consecutive patients with colorectal adenomas were recruited in this study. Two TMA blocks were constructed using four punches from each adenoma (one periphery, one deep, and two middle zones). The immunostaining of five markers (Ki-67, cyclin D1, ß-catenin, cyclooxygenase-2, and epidermal growth factor receptor) was analyzed, and the concordance between data obtained from TMAs and standard whole-tissue sections was evaluated by Spearman's correlation and kappa analysis.

Results: Colorectal adenoma exhibited zonal, heterogeneous expression patterns for all five markers. The concordance rates for the semiquantitative evaluation of markers between data from TMAs and whole sections ranged from 87% to 93% with corresponding kappa statistics of 77% to 90%. In addition, both quantitative and semiquantitative methods were used to score TMA sections, and good correlations between these two methods were shown for all five markers with intraclass correlation coefficients ranging from 0.5 to 0.8.

Conclusion: Our study indicates that TMA can be used to reliably assess the expression levels of Ki-67, cyclin D1, ß-catenin, cyclooxygenase-2, and epidermal growth factor receptor in colorectal adenoma tissues. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1719–26)

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