Do prostatic transition zone tumors have a distinct morphology?

Previous studies have proposed that the morphologic spectrum of prostatic glands of variable size with tall columnar cells displaying basally oriented nuclei and clear to pale pink cytoplasm (TZ-LOOK) is characteristic of the well to moderately differentiated component of transition zone (TZ) tumors. However, the specificity of these findings has not been well studied. In a recent report, we identified dominant peripheral zone (PZ) and TZ tumors situated anterior to the prostatic urethra. Currently, we evaluate the histopathologic features of 215 dominant tumors, including 63 TZ and 73 anterior PZ lesions and an additional cohort of 79 posterior PZ tumors, in radical prostatectomy specimens, to identify the prevalence of this morphology in tumors of different zonal origin. Each dominant tumor was assigned a TZ-LOOK extent score of 0 to 4, with 0 = no such morphology, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, and 4 = >75%. Overall, 121/215 (56%) tumors showed some degree of this histology, including 56 of 63 (89%) TZ tumors and 65 of 152 (43%) PZ tumors (P<0.0001). Thirty-seven of 215 (17%) lesions had scores of 3 to 4, with 31 (84%) of these being of TZ origin. However, only 31/63 (49%) TZ tumors had >50% TZ-LOOK. Among PZ tumors, 6/152 (4%) had predominant (>50%) TZ-LOOK morphology, yet 23/152 (15%) of all PZ tumors and 23/65 (35%) of PZ tumors displaying any degree of TZ-LOOK had scores of 2 to 3 (>25%; nonfocal). In tumors of both zones with predominant (scores 3 to 4; >50%) TZ-LOOK histology, darker glands of usual acinar adenocarcinoma was often seen at the periphery. Conversely, in tumors with nonpredominant TZ-LOOK (scores 1 to 2; 50% of this histology are very likely of TZ origin, but this scenario occurs in only half of TZ tumors. Importantly, the TZ-LOOK is nonfocal in up to 35% of PZ tumors exhibiting any degree of this morphology. Given this lack of specificity, caution should be exercised in assigning zone of origin based on this histologic appearance, especially in limited samples such as prostate needle biopsy.     

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.     

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.     

Clinicopathological analysis of transition zone cancer of the prostate: the clinical significance of coexistent non-transition zone cancer foci]

BACKGROUND: Dominant cancer of transition zone origin of the prostate (TZ cancer) has been frequently detected, because ultrasound-guided systematic biopsies have been generalized. In cases of TZ cancer, we attempted to determine clinical significance of coexistent non-TZ cancer foci. MATERIALS AND METHODS: Twenty cases with TZ cancer who underwent radical prostatectomy or cystoprostatectomy were clinicopathologically evaluated using step-sectioned specimens. RESULTS: In TZ cancer foci, there were extraprostatic extension in 5 cases (25%), seminal vesicle invasion in 2 cases (10%), positive surgical margin in 6 cases (30%) and bladder neck invasion in 4 cases (20%). The extraprostatic extension and the positive surgical margin occurred at the anterior or anterioapical portion of the prostate in all the cases. On the other hand, 17 (85%) had coexistent non-TZ cancer foci. In non-TZ cancer foci, there were extraprostatic extension in 3 cases (15%), seminal vesicle invasion in 1 case (5%) and positive surgical margin in 1 case (5%). The extraprostatic extension and the positive surgical margin occurred at the posteriolateral portion of the prostate in all the cases. In 3 cases a coexistent non-TZ cancer focus showed the extraprostatic extension, the seminal vesicle invasion or the positive surgical margin, although a TZ cancer focus were organ-confined. CONCLUSION: We should add attention to coexistent non-TZ cancer foci in TZ cancer cases. Particularly, we believe that pre-operative evaluation of non-TZ cancer foci is needed in TZ cancer cases of the candidates for nerve-sparing radical prostatectomy.     

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.     

Transitional zone and anterior peripheral zone of the prostate. A correlation of small-volume cancer in the biopsy cores and high psa with positive anterior margins in radical prostatectomy specimens

Introduction: Prognostically significant prostatic adenocarcinomas (PAC) may pose diagnostic problems if they were localized in the anterior peripheral zone (APZ) or transitional zone (TZ). Materials and Methods: 108 cases of PAC were reviewed along with serum PSA and TRUS biopsies. The PACs were divided into 22 TZ, 17 APZ and 69 posterior peripheral zone (PPZ) PACs according to the location of the main tumor mass in the TZ and anterior or posterior half of the peripheral zone in the radical prostatectomy (RP) specimens. Results: In comparison with PPZ PAC, TZ PAC had a higher cancer volume in RP specimens (4 +/- 2.1 vs. 2.5 +/- 1.7 cm3, p < 0.01), a higher serum PSA (16.5 +/- 9.8 vs. 8.4 +/- 4.5 microg/l, p < 0.001), a biopsy with a small cancer volume (3.8 +/- 2.1 vs. 11.8 +/- 9.4 mm, p < 0.005), and a lower Gleason's score (4.8 +/- 2.1 vs. 6.5 +/- 1.7). APZ PAC was characterized by the cancer volume in RP and biopsy and PSA intermediate between those of TZ and PPZ PAC. Among 24 PACs with a total cancer core length of <3 mm, 19 cases were from the TZ and APZ groups and also had a higher cancer volume and PSA than those from the PPZ group (2.9 +/- 1.8 vs. 1.5 +/- 1.3 and 13.7 +/- 8.3 vs. 9.6 +/- 4 microg/l, respectively). Furthermore, there was a better correlation coefficient (r(2)) of tumor volume in the biopsy and RP for PPZ than for all zones PAC (r2 = 0.75 vs. 0.29). TZ and APZ carcinomas were associated with extension or satellite nodules of PAC in the PPZ that may be diagnosed with biopsies. These PACs were associated with positive anterior resection margin due to extracapsular extension of the carcinoma or intracapsular dissection in 6 and 5 cases respectively. Conclusions: TZ and APZ PACs accounted for the poor correlation between the tumor volume in the biopsy and the RP, and were associated with positive anterior resection margins. One core biopsy with a total cancer core length of <3 mm and PSA >10 microg/l are suspicious for TZ and APZ PCA in patients with undetectable tumors with DRE or TRUS. Clinically insignificant PACs tend to be associated with cancer core <3 mm and PSA <10 microg/l.     

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.     

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.     

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.     

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.     

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.     

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker

PURPOSE: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer. MATERIALS AND METHODS: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy. DPIV activities were measured by glypro-p-nitroanalide hydrolysis. RESULTS: DPIV activities were significantly higher in TZ than in PZ tissues in men with no evidence of malignancy. However, activities in EPS were negatively associated with TZ volume and positively associated with PZ volume. Mean and median DPIV activities in EPS from men with biopsy determined cancer were significantly higher than in men with no evidence of malignancy. DPIV activities in TZ and PZ biopsies were higher in men with cancer but most markedly in the PZ. CONCLUSIONS: These data indicate that secreted DPIV originates from the TZ and PZ. Increased DPIV activities in cancer are strongly associated with the PZ, which is the zone most commonly involved with cancer. Measuring DPIV levels in expressed EPS or post-digital rectal prostate examination urine may be useful for evaluating men for prostate cancer.     

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.     

Evaluation of a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional prostate models

AIM: We evaluated a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional (3D) prostate models. METHODS: Two 3D prostate models with a volume of 25 cc or 50 cc were constructed from computed tomographic images of radical prostatectomy specimens. The peripheral zone (PZ) and transition zone (TZ) were arranged in the prostate models according to the anatomical information. Four thousand patterns of cancer lesions were automatically inserted into each prostate model with a proportion of 75% in PZ and 25% in TZ. Average hit rates (AHR) in prostate models were evaluated both with an increased number of biopsy cores and various angles of virtual needle biopsy. The influence of adding secondary tumors for hit rates was also evaluated. RESULTS: For both sizes, the laterally angled biopsy in 4-8 core biopsy schemes showed higher AHR than the vertical plane biopsy, while the vertical plane biopsy in 10-18 core biopsy schemes showed higher AHR than the laterally angled biopsy. A higher number of biopsy cores increased the AHR of secondary tumors. CONCLUSIONS: Our results suggest that it is important in prostate cancer detection to change the needle placement according to the number of biopsy cores and the size of the prostate.     

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.     

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.     

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.     

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.     

Improving prostate cancer detection with an extended-core transrectal ultrasonography-guided prostate biopsy protocol

OBJECTIVE: To investigate whether taking two transition zone (TZ) and four lateral peripheral zone (PZ) biopsies in addition to routine parasaggital sextant biopsies would improve detection rates in men with suspected prostate cancer. PATIENTS AND METHODS: The study included 493 consecutive men (mean age 68.7 years, sd 8.2) with elevated serum prostate-specific antigen (PSA) levels and/or abnormal findings on a digital rectal examination who underwent transrectal ultrasonography-guided prostate biopsy. In addition to sextant biopsies, six further biopsies were obtained, two from the TZ (mid-gland) and four from the lateral PZ (base and mid-gland). Pathological findings for the additional biopsies were compared with those of the sextant regions. RESULTS: Prostatic adenocarcinoma was diagnosed in 164 of the 493 (33%) men biopsied. Men with cancer were older, had smaller prostates and higher median PSA levels than men with negative biopsies. Sextant biopsies were positive for cancer in 133 of 164 (81%) men. All three sets of biopsies were positive in 53 (32%) cases. In 50 (30%) men both the sextant and lateral PZ biopsies were positive, while in six (4%) men, both sextant and TZ biopsies were positive. Thirty-one (19%) tumours were not detected by sextant biopsies, 10 (6%) where the lateral PZ biopsies alone were positive, 17 (10%) where the TZ biopsies alone were positive and four (3%) where both the TZ and lateral PZ together were positive. There were no differences in median PSA concentration, total prostate volume or TZ volume between men with an isolated TZ cancer and men with cancer elsewhere in the prostate. However, 77% of men with TZ cancer had a PSA of > 10 ng/mL, compared with 60% of men with cancer at other sites within the prostate (P = 0.015). CONCLUSION: An extended-core biopsy protocol significantly improves the detection rate for prostate cancer when compared with the standard sextant biopsy protocol alone. Routine TZ biopsies should be considered for men with serum PSA levels of >10 ng/mL.