Proliferative tumor doubling times of prostatic carcinoma

Abstract

Prostate cancer (PCa) has a variable biology ranging from latent cancer to extremely aggressive tumors. Proliferative activities of cancers may indicate their biological potential. A flow cytometric assay to calculate maximum proliferative doubling times (T(max)) of PCa in radical prostatectomy specimens after preoperative in vivo bromodeoxyuridine (BrdU) infusion is presented. Only 4/17 specimens had tumors large enough for flow cytometric analysis. The T(max) of tumors was similar and ranged from 0.6 to 3.6 months. Tumors had calculated doubling times 2- to 25-fold faster than their matched normal tissue. Variations in labeling index and T(max) were observed within a tumor as well as between different Gleason grades. The observed PSA doubling times (PSA-DT) ranged from 18.4 to 32.0 months, considerably slower than the corresponding T(max) of tumors involved. While lack of data for apoptotic rates is a limitation, apparent biological differences between latent versus aggressive PCa may be attributable to variations in apoptotic rates of these tumors rather than their cell proliferative rates.

Figure 1

(a) Histogram 1: auxiliary peak red fluorescence versus red fluorescence, and (b) histogram 2: BrdU-FITC green fluorescence versus propidium iodide red fluorescence.

Figure 2

Gleason pattern 3 carcinoma with BrdU incorporated into the DNA of dividing cells (magnification 40X).

Figure 3

Distribution of BrdU incorporated cell nuclei within Gleason pattern 4 glands (magnification 100X).