DNA heterogeneity determined by flow cytometry in prostatic adenocarcinoma--necessitating multiple site analysis.

Although DNA ploidy analysis of prostate cancer is generally associated with grade, stage, clinical outcome, and responsiveness to androgen therapy, one possible reason cited for contrary reports may be tumor heterogeneity. A preliminary report using flow cytometric analysis of punch biopsies demonstrated DNA heterogeneity in five of nine patients. We evaluated 75 patients by cutting whole mounts of formalin fixed prostatectomy tissue every 0.6 cm. All malignant areas and a selected normal area were circumscribed, excised, remounted, and 1-3 50 mu thick sections removed. The nuclei were extracted by a Hedley technique and the DNA stained with propidium iodide. Each whole mount had an average of 1 distinct malignant area (range of 1-6 areas per whole mount block). Nuclei were analyzed on a Becton Dickinson (San Jose, CA) FACScan flow cytometer equipped with RFIT DNA software program. After excluding histograms with CVs > 8.0% and/or "suspicious" diploid histograms having a right "shoulder," 75 or 87 patients still had > or = 2 malignant sites available for analysis (average 4, range 2-9 malignant sites/patient). The 322 histograms had an average CV of 4.4%. Thirty of 75 patients (40%) showed DNA heterogeneity in multiple samples taken from the same prostate. There were 37 prostates with only diploid (D), 1 with only tetraploid (T), 7 with only aneuploid (A), 20 with D plus A, 7 with D plus T, 2 with D plus T plus A, and 1 with a D plus suspected hypodiploid DNA content. Exclusion of the tetraploid and "near diploid aneuploid" cases still resulted in 16% (12/75) of the patients having a diploid versus aneuploid DNA content heterogeneity. Because 40% of the prostates contained a different ploidy depending on which area was sampled, this report suggests multiple sites of malignancy must be analyzed to more accurately assess the ploidy status of prostatic adenocarcinoma.

DNA analysis by flow cytometry of paraffin embedded core biopsies of the prostate.

The majority of literature concerning DNA analysis of prostate cancer involves testing formalin-fixed prostatectomy tissue, fresh or formalin-fixed transurethral resections of the prostate (TURP), or fresh core biopsies. We were interested if flow cytometry could analyze the DNA of formalin-fixed, paraffin-embedded, core biopsies separated into normal versus malignant segments. Of the 50 potentially available samples for analysis representing 11 controls of normal core tissue and 39 core biopsies from the 11 patients, one patient had no normal tissue, one core had no malignancy, and three cores had no tissue visibly remaining in the paraffin blocks for analysis. Therefore, of 45 actual samples available for processing, sometimes representing segments as small as 0.2 cm, separate segments containing malignant glands or normal glands were excised from the blocks, and processed separately by the Hedley technique. Forty-four of the 45 available samples produced interpretable DNA histograms as defined by discernible G0/G1 peaks, a calculable cell cycle analysis, and the qualitative appearance of a "smooth" histogram appearance, reflecting sufficient nuclei were analyzed. This is the first report to our knowledge where flow cytometry has successfully been used to analyze paraffin blocks of core biopsies which were, in addition, separated into malignant versus normal enriched segments.

Comparing clinical staging plus transrectal ultrasound with surgical-pathologic staging of prostate cancer.

Twenty-five men with histopathologic diagnosis of prostatic adenocarcinoma were staged utilizing traditional staging modalities and transrectal ultrasound of the prostate (TRUSP). A comparison was then done with surgical-pathologic stage. TRUSP accurately predicted the local extent of disease in 84 percent of patients, while digital rectal examination understaged in 64 percent of patients. TRUSP is a valuable adjunct to staging prostate cancer prior to definitive therapy.

Transrectal ultrasound and fine needle aspiration for malacoplakia of the prostate.

Clinically, malacoplakia of the prostate gland may mimic prostatic carcinoma. We report a case of prostatic malacoplakia in which transrectal ultrasound of the prostate was most compatible with carcinoma. However, fine needle aspiration cytology and biopsy revealed the classical histopathological features of malacoplakia so that a correct diagnosis could be made.