DNA flow cytometry measurements as surrogate endpoints in chemoprevention trials: clinical, biological, and quality control considerations.
DNA flow cytometric evaluation of S-phase fraction (SPF) is a strong and consistent predictor of relapse-free survival in the node-negative breast cancer patient. As such, it can be implicated as a marker of tumor aggressiveness and has been shown to be an independent predictor of outcome in a multivariate setting. Measurement of ploidy status is less well-defined as a marker of prognosis, but may be an important marker of response to therapy. Estimation of DNA ploidy and proliferative capacity by flow cytometry can be obtained from virtually any type of specimen, including fine needle aspirates, fresh or frozen material, as well as formalin-fixed, paraffin-embedded material, as long as there is a sufficient number of tumor nuclei for assay. Therefore, the assay has clinical relevance in predicting relapse, as well as providing flexibility for sample preparation. In addition, flow cytometric measurements are biologically relevant markers. In general, DNA index is a good estimate of total chromosome number. SPF, using sophisticated modeling algorithms, shows good correlation with thymidine labeling index and/or bromodeoxyuridine incorporation, two standard assays used to measure DNA synthesis in fresh tissue. Recently, preliminary data in locally advanced breast cancer have indicated that ploidy and/or S-phase may also be useful in predicting cellular response to chemotherapy. Although there is good justification for measuring these parameters, appropriate quality control and quality assurance measures must be incorporated into all aspects of the assay--from sample handling and preparation to interpretation of cell cycle and histogram data.(ABSTRACT TRUNCATED AT 250 WORDS)
Dressler
L G
LG
University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7305.
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D011786:Quality Control; D016196:S Phase; D016896:Treatment Outcome
D004273:DNA, Neoplasm