The advent of flow cytometric DNA analysis in the late 1970’s was soon followed by reports of the independent prognostic significance of tumor cell DNA content and/or proliferative activity in a number of human malignancies. Numerous additional publications soon appeared, many of which did not substantiate the independent prognostic significance of DNA analysis. In addition, interlaboratory variation in specimen preparation, analysis, data interpretation, and quality control lead to questions about the validity of some results. In 1996 a committee of the American Society for Clinical Oncology concluded that the existing data did not warrant the routine application of measurements of DNA ploidy or proliferation analysis. Since 1996, the utilization of DNA analysis has significantly decreased, and it is most often performed in patients with node-negative breast carcinoma and other tumors where the clinical correlation is strongest.
However, recent technological innovations may lead to a revival of interest in clinical DNA analysis. In this regard, Bagwell modified DNA analysis to optimize the accuracy of DNA ploidy and S phase in nodenegative breast cancer, eliminate spurious technical inconsistencies, and apply standardized modeling rules to data analysis and interpretation. Furthermore, the authors developed a prognostic model that combines DNA ploidy and the S phase into a Relative Risk Index (RRI).
Multiparametric DNA analysis using cytokeratin expression to exclude normal background cells has also been shown to improve the predictive value of the measurements.(15.)