Response to Larry Seamer

David Hedley (david_hedley@pmh.toronto.on.ca)
Wed, 17 Sep 1997 07:59:02 -0500

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.