Peripheral Zone Prostate Cancer Research Articles

Biological determinants of cancer progression in men with prostate cancer.

The recent increase in ability to diagnose prostatic adenocarcinoma has created a dilemma for treatment decisions. To determine whether prostate cancer progression is associated with a modified version of the Gleason grading system together with selected morphologic and clinical variables. Retrospective analysis of a cohort of patients with peripheral zone prostate cancers who underwent surgery between August 1983 and July 1992. University hospital. Radical prostatectomy specimens from 379 men treated only by surgical excision were prospectively studied for 8 morphologic variables using previously standardized techniques. Variables were percentage of each cancer occupied by Gleason grade 4/5 (% Gleason grade 4/5, the Stanford modified Gleason scale), cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin, prostate weight, and preoperative prostate-specific antigen (PSA) level. Biochemical progression of prostate cancer as indicated by serum PSA level of 0.07 ng/mL and increasing. Cancer grade expressed as % Gleason grade 4/5 and cancer volume were highly predictive of disease progression. In a Cox proportional hazards model that included % Gleason grade 4/5, the traditional Gleason score was not an independent predictor of treatment failure. Positive lymph node findings and intraprostatic vascular invasion were the only other variables that remained significant at the .01 level. The % Gleason grade 4/5, cancer volume, positive lymph node findings, and intraprostatic vascular invasion were independently associated with prostate cancer progression, defined by an increasing PSA level. Techniques to accurately measure cancer volume and % Gleason grade 4/5 are needed to better predict which patient will experience cancer progression. The commonly accepted predictors of progression-capsular penetration and positive surgical margins-were not independently predictive of failure after radical prostatectomy.

GENETIC ALTERATIONS IN INCIDENTALLY DIAGNOSED, TRANSITIONAL ZONE PROSTATE CANCER: A SEVEN YEAR FOLLOW-UP

To investigate the frequency and prognostic significance of genetic alterations in incidentally diagnosed, transitional zone prostate cancer. Twenty-six incidentally diagnosed, transitional zone cancers were examined by the PCR for genetic alterations on chromosomes 8p and 13q and by immunohistochemistry for alterations of the expression of the cell-cycle regulatory proteins RB1 and p53 and of the cell adhesion molecules E-cadherin and alpha-catenin. All of the tumors had at least one molecular abnormality (median 2.0 range 1 to 4). Allelic loss on 8p occurred in 37% and on 13q in 50% of informative tumors. Abnormal expression of pRb was found in 67%, of p53 in 33%, of E-cadherin in 36% and of alpha-catenin in 43%. In addition microsatellite instability was found in 23% of tumors. Only loss of expression of alpha-catenin was found to have prognostic importance. Genetic alterations were common, but, apart from alpha-catenin, did not appear to be related to tumor progression. The lack of prognostic significance is likely to be due to the multifocal nature of prostate cancer, but may also relate to qualitative differences between transitional zone and peripheral zone prostate cancers.

Is there really a difference between peripheral zone and transition zone prostate cancer?

Is there really a difference between peripheral zone and transition zone prostate cancer?

A Comparison of the Morphological Features of Cancer Arising in the Transition Zone and in the Peripheral Zone of the Prostate

To determine the characteristics of transition zone and peripheral zone prostate cancer, we examined a series of 42 stage A and 54 stage B radical prostatectomy specimens with particular attention to the number of separate foci of cancer, zone of origin, volume and grade of each focus, and presence of severe intraductal dysplasia (high grade prostatic intraepithelial neoplasia), extracapsular extension and seminal vesicle invasion associated with cancer in each zone. We found that there were fundamental differences between transition zone and peripheral zone cancers, and that the features that characterize these tumors were apparent in stages A and B disease.Although the total tumor burden was similar in stages A (3.98cc) and B (4.56cc) disease, stage A cancer tended to be multifocal (3.1 tumors per prostate) and more diffuse. While 81% of stage A prostate specimens contained a tumor of transition zone origin and 93% had cancer of peripheral zone origin, transurethral resection of the prostate sampled a transition zone cancer in 77% and a peripheral zone cancer in 31% (8% had both types). Stage B cancer tended to be more focal (2.3 cancers per prostate). All stage B prostate specimens contained a peripheral zone cancer and 43% had a transition zone cancer as well. In only 1 stage B cancer patient was the transition zone tumor the palpable or index cancer.In stages A and B disease, peripheral zone tumors were less well differentiated (median Gleason sum 6 and 7) than transition zone tumors (5 and 5, respectively) and more likely to extend through the capsule (44% versus 11%). Seminal vesicle invasion arose from 19% of the peripheral zone but none of the transition zone cancers. Peripheral zone tumors were almost always (93%) associated with high grade prostatic intraepithelial neoplasia, while none of the transition zone cancers was so associated. For peripheral zone disease there was a moderate correlation between volume and grade (tau = 0.46, p <0.001) so that the larger the tumor the higher the Gleason sum but within transition zone disease this correlation was poor (tau = 0.23) and not statistically significant (p >0.05). Extracapsular extension occurred at a smaller volume with peripheral zone cancer (mean 3.86, minimum 0.06cc) than transition zone cancer (mean 4.98, minimum 0.39cc). Cancer that arises in the transition zone appears to have a different histogenesis, is associated with more favorable pathological features and may have less malignant potential than tumors that arise in the peripheral zone.