TESTING FOR TUMOR DNA STATUS

DNA testing on large portions of prostate cancer...such as TURP chips or prostatectomy tissue may give useful information in some cases. But, DNA testing on these very skinny diagnostic core biopsies is fraught with possibilities of serious miss-information...the tissue pieces are too small!

DNA testing is technically demanding and requires adequate numbers of intact cancer-cell nuclei.
If performed by flow cytometry (FCM), the core biopsy tissues must be processed so as to dislodge nuclei; and all of the nuclei will be tested in the flow stream. The instrument is unable to discern cancer nuclei from normal-tissue nuclei. A minimum of 10,000 nuclei are needed in order to produce a reliable DNA ploidy result AND an S-phase result. This would require at least 3 core biopsies nearly filled with cancer, the cores totally devoted to that one DNA test. If much greater amounts of cancer are available, the flow stream can be "gated" so that non-cancer nuclei are ignored. When a patient is considered, based on many bits of evidence, to have bulky or wide-spread cancer in the gland, it is plausible to rebiopsy and send all of the cores for DNA testing by FCM.

If performed by image analysis (IA), at least 100 intact cancer nuclei are required for ploidy results and many more for S-phase; and, sections are stained on slides in a fashion similar to the diagnostic slides. An experienced operator selects each separate cancer nucleus and tests it; theoretically, only even small patches of cancer here and there between normal cells can be accurately assessed.

ONE PROBLEM: for DNA testing, either FCM or IA

The tissue sections must be over twice as thick for either DNA test as for diagnostic slides in order to get the intact nuclei. Interestingly, some of our cancer case diagnoses are made on diagnostic slides containing hardly 100 cancer nuclei (intact or in parts) on the whole slide frame!

Keep in mind that skinny needle biopsies are done primarily and foremost in order to FIND a cancer and that diagnosing benign cores vs.. malignant cores is the top priority question to be answered. That being so, we have always used up the cores in making thin (not DNA thick) paraffin ribbons for a maximum shot at finding any cancer in the cores sent to us. Dr. David Bostwick tells me (7/98)that even Mayo Clinic, processing thousands of biopsy cases per year...a majority to also include DNA status...has not found a steady use for DNA status information on biopsies. Therefore, we opt for production of thin ribbons and a full-court-press effort at finding the cancer if it is there.

In the meantime (2000-2015), there has been a revolution in molecular testing, HERE.

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(posted March 2000)