Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones

BACKGROUND: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin. METHODS: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification. RESULTS: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers. CONCLUSIONS: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.     

Differences in biopsy features between prostate cancers located in the transition and peripheral zone

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.     

Prognostic significance of prostate cancer originating from the transition zone

PurposeTransition zone (TZ) cancers are reported to have better biochemical relapse-free survival (bRFS) after radical prostatectomy (RP) than cancers from the peripheral zone (PZ). To understand the influence of tumor location, we compared bRFS for TZ and PZ cancers stratified for risk using known clinical and pathological prognostic factors.Patients and MethodsThe surgical pathology and outcomes of 494 patients were reviewed. Cancers originating from the TZ and PZ were identified from step sectioning of surgical specimens and tumor mapping. Univariate and multivariate analyses of bRFS after RP were compared.ResultsTZ cancers were present in 89 (18%) patients. On univariate analysis, most factors predicted bRFS, although cancer location did not: 5-year bRFS was 85% for TZ vs. 77% for PZ (P = 0.12). However, on multivariate analysis, all factors except SV involvement were significant, including TZ cancer location (P = 0.04, HR = 1.88 [1.02–3.47]). Interestingly, TZ location was correlated with improved 5-year bRFS for cancers > 2 cc (81% for TZ vs. 65% for PZ, P = 0.017), for preop PSA >10 (80% for TZ vs. 59% for PZ, P = 0.027), and for PSAV > 2 (85% for TZ vs. 66% for PZ, P = 0.08). However, TZ cancers showed no difference in outcome for small volumes, low preop PSA, low PSAV, or high Gleason grade.ConclusionsTZ cancers that are large, with high preop PSA, low Gleason scores, and high PSAV show better outcomes than their PZ counterparts. However, high-grade cancer tumor location had no apparent influence on outcome. Tumor location could be considered in subsets for optimal prognostication.     

Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome.     

Does transurethral resection of the prostate facilitate detection of clinically significant prostate cancer that is missed with systematic sextant and transition zone biopsies?

BACKGROUND: A prospective study was conducted to determine whether transurethral resection of the prostate (TURP) facilitates detection of prostate cancer that is missed with systematic sextant biopsies associated with transition zone (TZ) biopsies. METHODS: A total of 139 consecutive patients underwent transperineal TZ biopsies of each lobe in addition to a transrectal systematic sextant peripheral zone (PZ) biopsy. Patients whose biopsies were negative for cancer received TURP for relief of lower urinary tract obstruction when indicated. RESULTS: Cancer was detected in biopsy specimens of 40 patients. Of these cancers, 18 originated in the PZ alone and 22 were located both in the TZ and the PZ. No cancers were detected in the TZ alone. Of 99 patients who were proven not to have cancer by the biopsies, 18 were indicated for TURP. Five of these patients (28%) had cancer in the resected tissues. All cancers were clinically organ confined and their Gleason sum scores were 2-5. Cancer-positive chips accounted for less than 10% of all resected specimens. Of the 66 patients with negative biopsies and without indication for TURP, four (6%) were revealed to have an elevation of the serum PSA level during follow up. They were later proven to have cancer by a second biopsy. CONCLUSION: Routine use of TZ biopsy is not warranted for detection of cancer. Transurethral resection of the prostate can detect cancers in patients with negative PZ and TZ biopsies. However, cancers detected by TURP may not always be clinically significant and only four of 66 patients who were not indicated for TURP and received a close follow up were later found to have cancer, although their follow-up period was short. Thus, it still remains to be elucidated whether TURP is necessary for all patients with negative biopsies of the prostate.     

Zonal origin of localized prostate cancer does not affect the rate of biochemical recurrence after radical prostatectomy

OBJECTIVE: To investigate whether transition zone (TZ) prostate cancers demonstrate different rates of biochemical recurrence after radical prostatectomy compared to peripheral zone (PZ) cancers. METHODS: In 1262 consecutive patients treated with radical prostatectomy, computerized planimetry defined tumour origin as either TZ tumours (>70% TZ location) or PZ. Kaplan-Meier and multivariate Cox regression models tested the association between zonal origin and the rate of biochemical recurrence (prostate-specific antigen >0.1ng/ml and rising). We used the Harrell's concordance index to quantify the accuracy of various Cox regression models. RESULTS: TZ prostate cancers were diagnosed in 115 patients (9.1%). Biochemical recurrence was recorded in 16 TZ and in 201 PZ prostate cancers patients. In multivariate Cox models, the rate of biochemical recurrence was not significantly different between TZ and PZ prostate cancers (p=0.4). Combined multivariate predictive accuracy of biochemical recurrence predictions was 81.2% accurate when zonal origin was included versus 81.0% when zonal origin was omitted. CONCLUSIONS: The zonal origin of prostate cancers does not affect the rate of biochemical recurrence after radical prostatectomy.     

Biochemical recurrence following radical prostatectomy: a comparison between prostate cancers located in different anatomical zones

BACKGROUND: To assess whether differences of biochemical recurrence after radical prostatectomy exist between prostate cancers located in the transition zone (TZ) and peripheral zone (PZ). METHODS: The 5-year biochemical recurrence rate of 307 patients was evaluated. A serum prostate specific antigen (PSA) level > or =0.1 ng/ml was defined as biochemical failure. Cancers were characterized by the location of the largest tumor area as TZ or PZ cancers. Pure PZ cancers were matched to TZ cancers by comparable pathological tumor stage, Gleason score, and surgical margin status. RESULTS: In 63 (20.5%) patients the largest tumor area was located in the TZ. A Kaplan-Meier analysis of the matched pairs calculated an 80% actuarial cure rate of TZ cancers compared to 89% of pure PZ cancers (log-rank test P = 0.742). CONCLUSIONS: TZ and pure PZ cancers matched by comparable pathological tumor stage, Gleason score, and surgical margin status showed no statistical difference in regard to biochemical cure following radical prostatectomy.     

Patterns of spread of adenocarcinoma in the prostate as related to cancer volume

BACKGROUND: Peripheral zone (PZ) and transition zone (TZ) cancers of the prostate remain confined to their zone of origin under 4 cc volume, with progressive molding to TZ boundary. In PZ cancer, growth in perineural spaces over 4 cc volume directs cancer toward the base, around subcapsular nerve trunks, and often transcapsular. This tendency to stereotyped patterns of cancer spread in the prostate is investigated systematically here for the first time. METHODS: Cancers in 571 radical prostatectomy specimens were sorted by zone of origin and tumor volume. A traced map of each cancer at 3 mm transverse intervals was assessed for location, contour, selected linear measures and the "transverse (largest) reference plane". RESULTS: Spread along prostate capsule characterized all but the smallest PZ cancers and was most extensive transversely. By 4 cc volume, most PZ cancers' transverse reference plane filled one side of PZ. Above 4 cc, bilateral spread, TZ invasion, and nodularity progressively increased, but dominant growth was toward the base along nerves to the superior pedicle; here capsule penetration was most common. TZ cancers arose mainly in anterior-mid TZ, invading anterior fibromuscular stroma (AFM) while small. AFM was massively invaded in many large tumors. Larger TZ cancers (> 4 cc) invaded anterolateral PZ but seldom penetrated posterior PZ. CONCLUSIONS: Patterns and extent of spread of carcinoma in the prostate are stereotyped following a few principles regarding stromal interactions. Using these, sequential maps were presented of evolving prostate cancer contours at consecutive increasing volumes.     

Significance of routine transition zone biopsies in Japanese men undergoing transrectal ultrasound-guided prostate biopsies

BACKGROUND: The objective of this study was to evaluate the clinical significance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)-guided systematic 8-core peripheral zone (PZ) biopsies. METHODS: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS-guided systematic biopsy of the prostate for the fi rst time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens. RESULTS: Prostate cancer was detected by 10-core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed significantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone. CONCLUSIONS: Routine TZ biopsy did not significantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy.     

Frequency and clinical significance of transition zone cancer in prostate cancer screening

Approximately 20% of prostate cancers originate in the transition zone (TZ). Although transrectal ultrasound (TRUS) and systematic biopsies have improved peripheral zone (PZ) cancer diagnosis, additional biopsies directed into the TZ may further improve cancer detection. To evaluate the frequency and clinical significance of TZ cancers, we added two TZ biopsies to the routinely performed sextant biopsies. Three hundred forty patients (aged 45–75) from our prostate-specific antigen (PSA) screening study (21,078 volunteers) with negative rectal examination findings underwent systematic and TZ biopsies with three-dimensional ultrasound equipment. All patients had elevated PSA levels according to age-specific reference ranges. Ninety-eight of 340 men (28.5%) had biopsies positive for cancer. Of these 98 cancers, 28 (28%) originated in the TZ only and 5 (5%) were located in the TZ as well as the PZ. Eight men showed TZ abnormalities on ultrasound images, of whom four had biopsies positive for TZ cancer. The TZ cancers detected were pathologically significant in 96% (27 of 28). Seventy-one percent (20 of 28) of pathologically staged cancers were found to be organ confined and all combined TZ and PZ cancers were advanced tumors. We conclude that TZ biopsies enhance the cancer detection rate in prostate cancer screening and should therefore be added to the routinely done sextant biopsies in men with PSA elevation and normal digital rectal examination findings. Prostate 30:130–135, 1997. © 1997 Wiley-Liss, Inc.     

Does benign prostatic hyperplasia originate from the peripheral zone of the prostate? A preliminary study

OBJECTIVE: To compare the histological characteristics, cell proliferation, apoptosis and biological features in benign prostatic hyperplasia (BPH) in the peripheral (PZ) and transition zone (TZ) of the prostate. PATIENTS AND METHODS: Tissue from BPH in TZ and PZ was obtained from 68 patients undergoing transrectal ultrasonography-guided biopsy and used for both morphometric analysis and immunohistochemical studies. The epithelial, stromal and luminal composition of the tissue was determined using a computer-assisted method for quantitative morphometric analysis. Apoptosis was detected as the apoptotic index (AI) using the TdT dUTP nick-end labelling assay. Cell proliferation was determined as the proliferation index (PI) using Ki-67 immunostaining. The expression of epidermal growth factor receptor (EGFR), transforming growth factor beta1 (TGFbeta1), androgen receptor (AR) and bcl-2 were assessed immunohistochemically. RESULTS: There was no difference in the stroma/epithelium ratio between PZ and TZ hyperplastic nodules (P > 0.05). The mean AI in epithelium was almost identical to the corresponding PI. In stroma, no apoptotic cells were detectable. There was a significantly higher PI and AI in the glandular epithelial cells in PZ hyperplastic than in TZ hyperplastic nodules, but no difference in PI of the stromal cells between PZ and TZ hyperplastic nodules. There was significantly higher expression of TGFbeta1 and lower expression of EGFR and bcl-2 in PZ than TZ hyperplastic nodules (P < 0.05). There was no difference in AR expression between PZ and TZ hyperplastic nodules (P > 0.05). CONCLUSIONS: These results indicate that some hyperplastic nodules in PZ might originate from the PZ, and the formation of these nodules might be modulated in a different way from that in the TZ.     

Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-β1 (TGF-β1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma–epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.     

Relationship between clinical stage and histological zone of origin in early prostate cancer: morphometric analysis.

A detailed morphometric analysis of 96 radical prostatectomy specimens (13 clinical stage A1, 29 A2, 34 B1 and 20 B2) was undertaken to examine the relationship of zone of origin to volume, grade and extraprostatic extension of cancer. In patients with stage A disease, transition zone (TZ) cancer (present in 81%) was significantly larger but of lower grade than peripheral zone (PZ) cancer (present in 90%). The total volume of cancer in stage A1 patients averaged 1.55 ml with 72% of TZ origin. In patients with stage A2 disease, tumour volume averaged 5.83 ml with only 57% of TZ origin. Specimens taken during transurethral resection of the prostate (TURP) revealed TZ cancer in 82% and PZ cancer either alone or with TZ cancer in 22%. The 9 patients with PZ cancer in the TURP specimen included 5 of the 11 with extracapsular extension and all 5 of those with seminal vesicle invasion. Every patient with stage B disease had PZ cancer which, in all except 3 cases, was of significantly larger volume and higher grade than any TZ cancer (present in 43%) in the same gland. In patients with stage B cancer, total tumour volume was 5.13 ml with 91% of PZ origin. TZ cancer tended to be well differentiated in all patients, even at large volumes, whereas PZ cancer was often moderately or poorly differentiated even at low volumes. In patients with stage B disease, TZ cancer appeared to be incidental and of no clinical importance, while in stage A patients PZ cancers were sometimes large, poorly differentiated and extended outside the prostate. Progression of a stage A cancer seems more likely to result from PZ cancer than TZ cancer, and the finding of PZ cancer in a TURP specimen should probably preclude its classification as stage A1.     

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.     

Is transition zone biopsy valuable in benign prostatic hyperplasia patients with serum prostate-specific antigen >10 ng/ml and prior negative peripheral zone biopsy?

OBJECTIVES: To evaluate the importance of transition zone (TZ) biopsy in benign prostatic hyperplasia (BPH) patients with serum prostate-specific antigen (PSA) >10 ng/ml and prior negative peripheral zone (PZ) biopsy and to estimate the sensitivity of TZ biopsy. MATERIAL AND METHODS: A total of 273 BPH patients with PSA >10 ng/ml and prior negative PZ biopsy underwent an extended biopsy protocol. In patients with a TZ volume <25 cm(3), four TZ biopsies were taken (two cores per side from the apex and base). In patients with a TZ volume > or =25 cm(3) (n=183), six TZ biopsies were taken (three cores per side from the apex, middle and base). Overall, 215 patients were subjected to either transurethral resection of the prostate (n=162) or open enucleation of the adenoma (n=53). RESULTS: The extended biopsy revealed prostate cancers in 21.2% of cases (58/273). The zonal distribution of the positive cores was as follow: PZ cancers only in 67.2% of cases (39/58), TZ cancers only in 13.8% (8/58) and PZ+TZ cancers in 19% (11/58). Overall, 73.6% (14/19) and 36.8% (7/19) of TZ cancers were detected at the apex and middle of the TZ, respectively, while no TZ cancers at all were detected at the base (p=0.00015). The incidence of carcinoma on definitive pathology was 5.6% (12/215). Consequently, TZ biopsy detected only 61.3% (19/31) of TZ cancers. The incidence of pure TZ cancers was 7.3%. On the chi(2) test, patient age, serum PSA, transrectal ultrasonography findings and PSA density did not correlate significantly with the detection rate of TZ cancer. Prostate volume (p=0.023), TZ volume (p=0.027) and PSA/TZ density (p=0.007) were predictive of TZ cancers. CONCLUSIONS: Although TZ biopsy was the sole site of cancer in only 2.9% of cases (8/273), it improved the cancer detection rate by 14% in this selected group of patients. The majority (74%) of TZ cancers were detected at the apex site. TZ biopsy has a low sensitivity (61%).     

Immunohistochemical Analysis of Radical Prostatectomy Specimens After 8 Months of Neoadjuvant Hormonal Therapy

Neoadjuvant hormone therapy (NHT) prior to radical prostatectomy (RP) results in residual foci of atrophic glands, which can be difficult to identify with hematoxylin-eosin staining, raising the possibility that the low positive-margin rates are an artifact of pathologic understaging. The purpose of this study was to evaluate changes in prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as proliferation marker Ki-67 and Bcl-2 oncoprotein, by immunostaining after 8 months of NHT. Twenty-nine men with clinically confined prostate cancer who received 8 months of NHT and had both pretreatment biopsy and RP specimens obtained at Vancouver Hospital constituted the treatment group. The control group consisted of 23 RP specimens from patients not receiving NHT. Sections were stained with antibodies against PSA, PAP, proliferation marker Ki-67, and the antiapoptosis protein Bcl-2. The PSA and PAP immunostaining were graded for percentage of positive tumor cells and intensity of staining, while Ki-67 and Bcl-2 staining was graded according to the percentage of positive tumor cells. Absent or low percentage-positive PSA and PAP staining was observed in 40% to 50% of the NHT-treated RP specimens but none of the needle biopsy or untreated control RP specimens. Low-intensity PSA and PAP staining was detected only in RP specimens after NHT treatment, and then in only 20% of cases. Low or absent Ki-67 staining was noted in 78% of the NHT- treated RP specimens, compared with only 13% of the matched pre-NHT needle biopsies and 26% of untreated RP specimens. The percentage of specimens with high (>5%) Ki-67 staining decreased from 37% in the pre-NHT needle biopsies to 8% in the NHT-treated RP specimens. Bcl-2 staining increased after treatment with NHT, with 20% of the needle biopsies having high (>5%) Bcl-2 staining compared with 53% of the NHT-treated RP specimens. The frequency of low Bcl-2 staining (<1%) decreased from 53% in the pre-NHT needle biopsies to 27% in the NHT-treated RP specimens. Although PAP and PSA staining decreased after NHT, both markers remain sufficiently positive to be used as epithelial markers to help detect residual foci of prostate cancer that are difficult to identify on H&E-stained slides after NHT. Increased Bcl-2 after NHT, even in early-stage disease, is consistent with its role in the prevention of apoptosis and progression to androgen independence. Low levels of Ki-67 staining indicates a low probability of proliferation and outgrowth of androgen-independent clones after 8 months of NHT.     

Clinicopathological study of prostate cancer patients who had a serum PSA level of more than 20 ng/ml and were treated by a radical prostatectomy

PURPOSE: In order to assess the validity of radical prostatectomy for the prostate cancer with PSA greater than 20 ng/ml, we reviewed the clinicopathological characteristics and prognoses of radical prostatectomy cases with PSA greater than 20 ng/ml. MATERIAL AND METHODS: Twenty-one radical prostatectomy cases who had a serum PSA level greater than 20 ng/ml were reviewed regarding their clinicopathological characteristics. Step-sectioned specimens were used for pathological evaluation. RESULT: The serum PSA level ranged from 21 to 65 ng/ml (median : 27 ng/ml). As for the clinical stage, there were 8 T1c cases, 5 T2b cases, 5 T2c cases, and 3 T3a cases (2001. TNM classification). According to the tumor location, 10 cases were diagnosed as peripheral zone (PZ) cancer, and 10 cases were diagnosed as transition zone (TZ) cancer. One case had several small cancer foci both in PZ area and TZ area. In 10 PZ cancer cases, 2 cases had lymph node metastasis, and 8 had seminal vesicle invasion. All of 10 PZ cancer cases showed extraprostatic extension, and 7 showed positive surgical margin. On the other hands in 10 TZ cancer cases, no cases had lymph node metastasis and seminal vesicle invasion. Five TZ cancer cases showed extraprostatic extension, and 6 showed positive surgical margin. The findings of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) were positive in all PZ cancer cases, but these findings were unclear in TZ cancer cases. In addition, no significant difference were observed between the PZ cancer cases and the TZ cancer cases regarding age, PSA, prostate volume, PSA density, cancer volume, and Gleason scores. PSA failure was observed in 9 PZ cancer cases, and 2 TZ cancer cases. CONCLUSION: Based on our findings, the prognosis of TZ cancer cases was better than that of PZ cancer cases among the radical prostatectomy cases with PSA greater than 20 ng/ml. Radical prostatectomy might be one of the effective treatment option for TZ cancer even if the PSA shows greater than 20 ng/ml. It seems to be important to detect TZ cancer properly based on DRE and TRUS findings.     

Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in prostate cancers: differences between tumours located in the transition zone and in the peripheral zone

OBJECTIVES: Transition zone (TZ) carcinomas of the prostate are thought to have less malignant potential than tumours that arise in the peripheral zone (PZ). It is unclear, however, whether this can be put down to anatomical reasons alone, or if there are further differences between tumours of both zones. METHODS: We examined Gleason scores, proliferation and apoptosis rates, microvessel density (MVD), p53 expression and bcl-2 expression in 76 paraffin-embedded radical prostatectomy specimens, containing 54 tumour foci in the TZ and 58 tumour foci in the PZ, matched for volume. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method was applied to detect apoptotic cells. Proliferation, MVD, p53, and bcl-2 were investigated by immunohistochemistry. RESULTS: There were significant differences between TZ tumours and PZ tumours in terms of the median Gleason scores (5 versus 7; P < 0.0001), the proliferation rate (3.2% versus 5.2%; P = 0.0003), and the MVD (68.5 versus 104; P = 0.0002), but the median apoptosis rate was quite similar (0.8% versus 0.9%). The p53 and bcl-2 expression were more frequent in PZ cancers as compared to TZ carcinomas (11% versus 2% and 27% versus 6%, respectively). CONCLUSION: There is evidence for lower Gleason scores as well as lower expression of markers related to tumour growth in TZ carcinomas of the prostate, which might contribute to a less malignant clinical behaviour as compared to PZ cancers.     

Transition zone biopsy and prediction of extraprostatic extension at radical prostatectomy

BACKGROUND: There is limited data in the literature that suggests that transition zone (TZ) biopsy might be useful for the prediction of extraprostatic extension (EPE) in clinically localized prostate cancer. We studied the role of TZ biopsy in the prediction of EPE. METHODS: Transition zone biopsies were performed in addition to systematic peripheral zone (PZ) biopsies between November 1995 and December 1999. During this period, 59 patients underwent radical prostatectomy for clinically localized disease. Final pathological results were compared with preoperative clinical and biopsy findings. RESULTS: Of the 59 patients who underwent radical prostatectomy, 46 had cancer only in the PZ cores and 13 had cancer both in the PZ and the TZ cores at the biopsy. Final histopathological results revealed EPE in 19 (32%) patients and positive surgical margins in 22 (37%). In univariate analysis of age, prostate-specific antigen (PSA), mean percentage of positive PZ cores, mean biopsy Gleason score and positive TZ biopsy, there was a significant difference for serum PSA levels (P = 0.021), presence of positive TZ cores (P = 0.018) and percentage of positive PZ cores in patients with and without EPE (P < 0.001). In multivariate analysis, the single independent predictor of EPE was the percentage of positive PZ biopsy cores (P = 0.0227). There was agreement between the side of positive TZ biopsy and EPE in seven of eight patients. CONCLUSION: Taking two TZ cores in addition to peripheral sextant biopsy did not result in better prediction of EPE. The relationship between TZ involvement and the presence of EPE can be investigated further in radical prostatectomy specimens.     

Characterization of the anatomical extension pattern of localized prostate cancer arising in the peripheral zone

Study Type – Diagnostic (non‐consecutive series)
Level of Evidence 3b

OBJECTIVES

To characterize the anatomical extension pattern of prostate cancer arising in the peripheral zone (PZ) in radical prostatectomy (RP) specimens and to evaluate its prognostic significance.

PATIENTS AND METHODS

Of 174 consecutive patients undergoing RP, 128 diagnosed as having PZ cancer (PZC) were enrolled. The maximum tumour area (MTA) and maximum tumour volume (MTV) in RP specimens were measured using digital planimetry. A circle with an area equal to the MTA, in which the central point was the intersection of the longest line of the MTA and the line perpendicularly bisecting the first line, was defined as a hypothetical extension area, regardless of anatomical structure. The area within this circle that did not overlap the MTA was defined as ΔTA.

RESULTS

There was a significant correlation between the MTV and ΔTA/MTA, introduced as a variable representing the degree of PZC extension along the anatomical shape of the PZ. The ΔTA/MTA in patients with a MTV of >5 mL was significantly greater than that in those with a MTV of ≤5 mL. Furthermore, ΔTA/MTA was significantly associated with several prognostic indicators, including extracapsular extension, surgical margin status and perineural invasion. Multivariate analysis identified ΔTA/MTA in addition to preoperative serum prostate‐specific antigen level, extracapsular extension and surgical margin status as independent predictors of biochemical recurrence after RP.

CONCLUSIONS

PZC tends to extend along the anatomical shape of the PZ during progression, resulting in higher ΔTA/MTA value in advanced PZC than that in early PZC.