As one of the organizers of the 1993 DNA Cytometry Consensus Conference, I would like to comment of Larry Seamer's open letter about clinical DNA analysis. The ASCO consensus on prognostic markers that was published in J Clin Oncol last year (vol 14:2843-2877) deserves reading by the clinical flow cytometry communuity. Unlike the 1993 consensus this was not written by cytometry specialists, but rather by a panel of experts with a much broader perspective. It is quite dismissive on the utility of DNA index and S-phase in colorectal and breast cancers, based on inconsistencies in the published literature. It seems quite likely that this report will have a negative impact on the use of DNA flow cytometry in clinical laboratories. Since I no longer do DNA flow cytometry in my own lab, I might be behind on the world literature since we reviewed it at the 1993 conference. However, it is my impression that since that meeting relatively few papers have appeared utilizing the more sophisticated techniques that we envisaged at Prout's Neck. For example, use of additional parameters such as cytokeratin to exclude non-malignant cells. I do not recall seeing any recent papers that show a significant improvement in the prognostic significance of S-phase in breast or colon cancer using additional parameters or refinements in technique. Therefore, if we were to reconvene the DNA consensus meeting I am not sure if we would have much new to say. This is not intended to be a snipe at the clinical flow community, and I would be very happy to be proven wrong. However, my own personal belief is that at this late stage we are not about to see a rush of studies that answer the question: "iwhat would be the prognostic significance of cell cycle analysis in breast cancer, if we used absolutely the best llow cytsometry technique available (e.g. carefully dissected fresh tissue, cytokeratin gating, CV's of <2%, ModFit for Windows 98 etc)?" I suspect that the laboratories with the resources, sophistication, and motivation to do such a study have moved on to more interesting questions, such as understanding the fundamental mechanisms of deranged cell cycle control in cancer. David Hedley Ontario Cancer Institute/Princess Margaret Hospital Toronto.
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