INTRATUMORAL NUCLEAR MORPHOLOGIC HETEROGENEITY IN PROSTATE-CANCER

Objectives. Tumor heterogeneity can be measured by quantifying varianc e of nuclear characteristics by image analysis. Heterogeneity of cell nuclear features correlated with increased local progression in prosta te cancer. In the present study, the influence of tumor heterogeneity on prostate-specific antigen (PSA) recurrence after radical retropubic prostatectomy was analyzed and tumor heterogeneity was compared in pa tients with and without neoadjuvant hormonal therapy. Methods. Retrosp ectively, radical prostatectomy material of 44 patients without and 12 patients with neoadjuvant hormonal treatment with a postoperative fol low-up of at least 4 years was studied. Each prostatectomy specimen wa s systematically embedded in paraffin, and each tumor area within the prostate was marked and analyzed by an image analysis system for 32 nu clear features comprising nuclear shape, size, DNA content, and chroma tin pattern. Several clinical features were available: preoperative se rum PSA, hemoglobin concentration, Karnofsky score, tumor stage, and G leason score. Results. Increased tumor heterogeneity, as expressed by differences in karyometric values between tumor areas in nuclear shape and chromatin pattern within the tumor, was significantly correlated with earlier PSA recurrence rate. As compared with nonpretreated patie nts, hormonally pretreated specimens showed smaller and less heterogen eous tumors. In particular, chromatin pattern heterogeneity was decrea sed in patients who underwent preoperative hormonal treatment compared with patients who were not pretreated. However, decreased heterogenei ty was accompanied by a higher percentage of aneuploid areas per tumor in the pretreated patients. Cox regression analysis showed that karyo metric determination of nuclear shape heterogeneity in combination wit h preoperative PSA level could predict time to PSA recurrence after ra dical prostatectomy in patients without hormonal pretreatment. Conclus ions. Increase in karyometric tumor heterogeneity in nuclear shape and chromatin pattern was correlated with a shorter PSA recurrence-free i nterval after radical prostatectomy. Preoperative PSA and karyometric tumor heterogeneity were the best predictors of PSA recurrence in a mu ltivariate analysis. Intratumoral heterogeneity was decreased in patie nts with prostate cancer who underwent neoadjuvant hormonal therapy. ( C) 1997, Elsevier Science Inc.