http://www.prostatelab.com/ploidy.htm

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The Prostate Lab www.prostatelab.com

"Focused on the Prostate since 1996"

DNA Ploidy 101 -A simple explanation (local link)

DNA Ploidy Analysis

[Written and Researched May 1996,]

By JR Oppenheimer, M.D., F.C.A.P.

Prostate pathologist on line

DrO@prostatelab.com

Both flow cytometry and and static image analysis have been used to determine DNA content (ploidy) of prostate cancer (CaP). DNA studies have shown that, as a group, patients with diploid cancers have longer disease free intervals and survival times than those with non-diploid tumors (Zinke, 1997). However, they may not be so helpful in predicting stage for an individual patient.

Because diploid tumors are more responsive to hormonal therapy (Zinke, 1992,1997), the Prostate Cancer Working Group (sponsored by the College of American Pathologists) has found that DNA ploidy studies are useful in patients with T3 or node-positive disease. As of June 1995, the Working Group does not recommend DNA analysis in T1, T2, or node-negative disease because of conflicting results in the literature (Grignon 1995). It still might be useful to have this data in case consensus is eventually reached, however.

Studies demonstrating the utility of DNA ploidy status have been performed on whole prostates obtained after RP. Since CaP is often a heterogeneous and multifocal disease, it doesn't necessarily follow that a tiny piece of tissue obtained on needle biopsy is representative of the lesion as a whole. Two reports have confirmed that ploidy status differs in different parts of an involved prostate (Greene,1991;O'Malley,1993). This intratumor variation in DNA ploidy suggests that multiple site sampling (possibly by fine needle aspiration) may be necessary to obtain accurate DNA measurements. Thus it may be misleading to assume that a tumor is entirely diploid when only a small fraction of it is sampled. Nevertheless, three studies have shown correlation between ploidy on needle biopsy and subsequent RP material (Leung,1994; Takai1994, Ross 1994).

The lack of mutually accepted standards limits the usefulness of ploidy analysis.

Both flow cytometry and image analysis techniques suffer from limitations.

Should DNA ploidy be determined from needle biopsy or RP tissue in order to determine prognosis?

In conclusion, it appears premature to place too much emphasis on DNA ploidy analysis performed on needle biopsy cores

Literature

1.Grignon DJ, Hammond EH. College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors - Report of the Prostate Cancer Working Group. Arch Pathol Lab Med 119:1122-1124(Dec95)

2.Ross JS, Fisher AH. Prediction of pathologic stage and postprostatectomy disease recurrence by DNA ploidy analysis of initial needle biopsy specimens of PCa. Cancer 74:2811-8(Nov94).

3.Takai K, Lieber MMJ. Static image and flow DNA cytomometry of PCa:studies of NB and RP specimens. J. Urol Path 2:39-47(1994).

4.Pindur A,Wheeler TM. DNA ploidy measurements in PCa: differences between image analysis and flow cytometry and clinical implications. (1994).

5.Hardt NS, Wajsman Z. Ploidy results in PCa vary with sampling method and cytometry technique. Mod Path 7(1):44-48(1994).

6.Leung C-S, Murray D. DNA image cytometry on prostatic carcinoma: a comparison of needle core biopsy specimens and subsequent prostatectomy specimens. Mod Path 7:195(1994).

7.Malley FP,McLean C. DNA heterogeneity in PCa: a flow cytometric mapping study with whole organ sections of prostate. Cancer 71:2797-2802(1993).

8.Shankey TV. Consensus review of the clinical utility of DNA content cytometry in prostate cancer. Cytometry(1993)14:497-500.

9.Falkmer UG. Methodologic sources of error in image and flow cytometric DNA assessments of the malignancy potential of PCa. Hum Path 23:360-7(1992).

10.Epstein JI,Partin A,Walsh PC. Correlation of PCa nuclear DNA, size, shape, and Gleason grade with pathological stage at RP. J. Urol 148:87-91(Jul92).

11.Zinke H, Larson-Keller JJ. Stage D1 prostate cancer treated by RP and adjuvant hormonal treatment. Cancer 70:311-323(1992).

12.Greene DR,Scardino PT. DNA ploidy by image analysis of individual foci of prostate cancer: a preliminary report. Cancer Res 51:4084-4089(1991).

13.Dejter SW, Lynch JH. Prognostic significance of DNA ploidy in CaP. Urol 33:361(1989).