Expression of differentiation-related genes in colorectal cancer: possible implications for prognosis

Although differentiation grade is an important prognostic factor for colorectal tumors, its usefulness is limited since its predictive value for tumor behavior is not very significant. This might be related to the subjective nature of histological assessment of differentiation grade, which allows the distinction of only three grades, and with limited reproducibility. Characterization of the differentiation process at the biochemical level may improve our understanding of normal and malignant differentiation, and is expected to provide molecular markers with higher discriminative potential than histomorphology. Several studies have compared gene expression in undifferentiated and differentiated colon carcinoma cells, and many differentially expressed genes have been identified. Some of these, including HLA class I, nucleophosmin, adenylosuccinate lyase, alpha-tubulin, and a novel gene designated Drg1, were found to be expressed at different levels in neoplastic as compared to normal tissue. In this review the rationale, implementation, and results of this approach are discussed, as well as the characteristics of two novel differentially expressed genes, ICT1 (previously named DS-1) and Drg1.