CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue...

The ability to use archival tissue to test externally valid hypotheses of carcinogenesis is dependent on the availability of population-based samples of cancer tissue. Tissue microarrays (TMAs) provide an efficient format for developing population-based samples of tissue. A TMA was constructed consisting of archival tissue from patients diagnosed with invasive colorectal cancer in the state of Hawaii in 1995. The population representativeness of the TMA was evaluated by comparing patient and clinical characteristics of TMA cases to that of all cases of colorectal carcinoma diagnosed statewide in 1995. Cytokeratin 20 (CK20) and cytokeratin 7 (CK7) immunohistochemistry was used to validate the utility of the TMA, and the expression of these proteins was correlated with patient and tumor characteristics. The TMA comprised tissue specimens from 286 patients representing 47% of all invasive cases diagnosed statewide in 1995. TMA cases were comparable to all invasive colorectal cases statewide with respect to age, sex, race/ethnicity, anatomic site, and survival. There were some differences between TMA cases and all cases with respect to tumor stage, histological classification, and treatment. There were significant differences in the relative expression of CK20 and CK7 proteins between malignant and normal tissues and by tumor stage. Advanced cancers were more likely to have CK20+/cytokeratin 7+ (CK7+) profiles than early-stage cancers, which were predominantly CK20+/cytokeratin 7- (CK7-). CK7+ expression was not correlated with anatomic location of carcinomas. This well-characterized TMA offers a powerful tool for testing hypotheses regarding colorectal carcinogenesis, including the identification of potential markers of neoplastic development and progression.