Active surveillance as a therapeutic option for patients with low-risk prostate cancer according to the 2014 International Society of Urological Pathology grading system: a review.

Extended prostate-specific antigen screening and the tightly focused execution of biopsies have resulted in an increased rate of detection, and thereby increased interventional treatment, of prostate cancer (PCa). The potential overdiagnosis and overtreatment of PCa patients have repeatedly been criticized in national and international literature. Controlled monitoring of patients in the setting of active surveillance (AS) can prevent overtreatment and the needless impairment of quality of life. The prerequisite for this treatment strategy is the diagnosis of low-grade/risk PCa. Since 2005, the modified Gleason grading system has been used for the histological assessment of PCa. In 2014, the International Society of Urological Pathology recommended a new prognostic grading system with five grades analogous to the modified Gleason score. This review discusses the importance of pathological histological analysis of PCa, particularly in the face of recent amendments, and sheds light on the significance of the new grading system for the diagnosis of low-grade/risk PCa with regard to the therapeutic option of AS.

Significance of Number and Localization of Positive Core Biopsies for the Identification of Prostate Cancer Eligible for Active Surveillance.

OBJECTIVE: Prostate cancer (PCa) patients fulfilling the Epstein criteria for insignificant disease are eligible for the treatment option of active surveillance (AS). Using the combined histological and cytological grading (Gleason/Helpap score), we aimed to investigate the significance of biopsy localization and tumor involvement in core needle biopsies as discriminators for insignificant cancer. STUDY DESIGN: Primary prostate biopsies of 1,285 patients were analyzed by the combined histological and cytological grading with regard to biopsy localization and tumor involvement per core. For patients diagnosed with pT2a stage PCa, core needle biopsies were further compared with the corresponding radical prostatectomy (RP) specimens. RESULTS: According to the combined histological and cytological grading, 95% of low-grade PCas (Gleason score 6/2a, prognostic grading group I) presented with a tumor involvement of < 10% in 1 core biopsy, whereas intermediate-grade tumors (prognostic grading group 2) displayed dissimilar tumor localization in 1 or both lobes with higher tumor volume. CONCLUSION: Our results indicate that the combined Gleason/Helpap grading may contribute to a more reliable identification of insignificant PCa with the option of AS. Ancillary criteria include the limitation of tumor involvement to < 10% per core, localized in 1 or 2 adjacent biopsies in only 1 lobe. Under this presupposition, > 90% of insignificant carcinomas concurred with low-grade PCa and stage pT2a tumors with negative margins after RP.

The Significance of Accurate Determination of Gleason Score for Therapeutic Options and Prognosis of Prostate Cancer.

The Gleason score (GS) to date remains one of the most reliable prognostic predictors in prostate cancer (PCa). However, the majority of studies supporting its prognostic relevance were performed prior to its modification by the International Society of Urological Pathology (ISUP) in 2005. Furthermore, the combination of Gleason grading and nuclear/nucleolar subgrading (Helpap score) has been shown to essentially improve grading concordance between biopsy and radical prostatectomy (RP) specimens. This prompted us to investigate the modified GS and combigrading (Gleason/Helpap score) in association with clinicopathological features, biochemical recurrence (BCR), and survival. Core needle biopsies and corresponding RP specimens from 580 patients diagnosed with PCa between 2005 and 2010 were evaluated. According to the modified GS, the comparison between biopsy and RP samples resulted in an upgrading from GS 6 to GS 7a and GS 7b in 65% and 19%, respectively. Combigrading further resulted in an upgrading from low grade (GS 6/2a) to intermediate grade PCa (GS 6/2b) in 11.1% and from intermediate grade (GS 6/2b) to high grade PCa (GS 7b/2b) in 22.6%. Overall, well-differentiated PCa (GS 6/2a) was detected in 2.8% of RP specimens, while intermediate grade (GS 6/2b and GS 7a/2b) and high grade cancers (≥ GS 7b) accounted for 39.5% and 57.4% of cases, respectively. At a mean follow-up of 3.9 years, BCR was observed in 17.6% of patients with intermediate (9.8%) or high grade PCa (30.2%), while PSA relapse did not occur in GS 6/2a PCa. In conclusion, adding nuclear/nucleolar subgrading to the modified GS allowed for a more accurate distinction between low and intermediate grade PCa, therefore offering a valuable tool for the identification of patients eligible for active surveillance (AS).

The Value of Prognostic Grouping of Prostatic Carcinomas for Urologists and Pathologists.

OBJECTIVES: To improve the prognostic stratification for different therapeutic options of prostatic carcinomas (PCa) with low and intermediate grade by combining Gleason grading with cytological findings and prognostic grade grouping. METHODS: We analyzed PCa after radical prostatectomy using the combined grading of Gleason and Helpap, which allows an exact differentiation particularly of low and intermediate grade tumors. Additionally, we attached time-interval and percentage value of recurrences of prostate-specific antigen (PSA) as well as death on disease (DoD) to the prognostic grade grouping. RESULTS: Carcinomas of group I/V are very low-grade tumors with very good prognosis without biochemical recurrence and DoD predestining for active surveillance (AS). The group II/V with low progress of PSA without DoD allows the options of an active treatment or AS and shows a prognostic separation of the intermediate group III/V. Within the high-grade groups, a differentiation is necessary between GS 7b (4 + 3), 8, and 9-10 regarding TNM staging and rate of DoD. Prognosis of GS 7b (4 + 3) group III/V is more favourable without DoD in contrast to group IV and V/V with cases of DoD. CONCLUSION: Morphologically prognostic classification by using combined grading may improve the prognostic stratification of patients with PCa.

The heterogeneous Gleason 7 carcinoma of the prostate: analyses of low and high grade (risk) carcinomas with criteria of the International Society of Urological Pathology (ISUP).

Prostate carcinoma (PCa) with Gleason score (GS) 7 has to be examined differentially regarding its prognosis. Using the criteria of ISUP and supplementations, we attempted to analyze the heterogeneity of PCa with GS 7 of biopsy and corresponding specimens of radical prostatectomies (RP). PCa of 530 patients were graded according to Gleason under additional consideration of the state of the nucleoli. Investigating the biopsy specimens, we determined the pattern of Gleason 4 of GS 7, the extension of the tumors in percent, and the number of biopsies containing tumor. In the corresponding specimens of RP, the grading and the state of TNM with margins were assessed. Carcinomas with GS 7 (4+3) in biopsy and RP specimens were unequivocally assigned to the group of high-grade tumors. Carcinomas with GS 7 (3+4) were significantly different from carcinomas with GS 6 when only few and small nucleoli in GS 6 were present (low grade type, p≤0.0001), but were similar to the GS 6 group when nucleoli were prominent (intermediary type, p=0.71). The intermediary group showed an upgrading rate of 36% from GS 6 to GS 7. Furthermore the correlation between organ-confined and non-organ-confined growth showed differences of 63% and 37% in the intermediary group (p=0.0001). The values of grading, staging, margins and metastases indicate that carcinomas of the prostate with the Gleason 3+4 pattern correspond to an intermediary group of carcinomas in contrast to high-grade (high risk) carcinomas with GS 7 and pattern 4+3.

Significance of Gleason grading of low-grade carcinoma of the prostate with therapeutic option of active surveillance.

INTRODUCTION: Active surveillance needs a precise grading diagnosis of a low-grade carcinoma of the prostate (Gleason score (GS) 6) within a small organ-confined tumor. However, how accurate is the gold standard of GS 6 in predicting a small pT2 carcinoma? To answer this question, we have analyzed grading systems in this study. METHODS: Prostatic carcinomas in biopsy and corresponding radical prostatectomy (RP) specimens of 960 patients were graded by the Gleason system in which glandular fusions and nucleolar stage (prominence and location) were considered. RESULTS: Using the modified Gleason grading, a high upgrading rate from the biopsy to RP specimens (GS 6-7) and in even 30% a non-organ-confined growth pattern (pT3) of GS 6 carcinoma in RP was found. When considering glandular fusion and the incorporation of the state of nucleoli within the Gleason grading, the agreement of score 6 between biopsy and RP specimens as well as the prediction of a pT2a tumor increased from about 80 to 90%. CONCLUSION: The combination of Gleason grading and grading of the nuclear and nucleolar features may help to identify patients eligible for active surveillance.

Combined histoarchitectural and cytological biopsy grading improves grading accuracy in low-grade prostate cancer.

OBJECTIVES: Accurate tumor grading on prostate biopsy represents the mainstay for therapy planning. Biopsy undergrading is a persistent diagnostic dilemma with therapeutic relevance. We questioned whether Gleason grading combined with an established alternative grading system incorporating cytological parameters improves grading accuracy. METHODS: Needle biopsies of 968 patients and the corresponding radical prostatectomy specimens were graded according to the Gleason grading system. In addition, all biopsies were graded according to the histo- and cytological grading system of Helpap. Biopsy Gleason grade, as well as the combined Gleason/Helpap grade, was compared with the final Gleason score and the pathological tumor-stage of the corresponding radical prostatectomy. RESULTS: In biopsy Gleason score 6 cancers, an upgrading was seen in 76.0% of the patients (98/129), and 30.2% of them (39/129) showed non-organ confined disease. In combined biopsy Gleason 6/Helpap 2a patients, a final Gleason score of 6 was found in 22 out of 24 patients (91.7%, P<0.0001), and all 24 patients showed organ-confined disease (pT2a). In biopsy Gleason 6/Helpap 2b cancers, a final Gleason score of 6 was found in just 9 out of 105 patients (8.6%), and the rate of organ-confined disease decreased to 62.8% (66/105, P=0.0001). In higher Gleason grades, combined biopsy grading failed to show a diagnostic benefit over sole Gleason grading. CONCLUSION: Combined biopsy Gleason/Helpap grading improves the identification of low-grade/low-stage cancers and might contribute to more precise therapy planning in prostate cancer management.

Modified Gleason grading. An updated review.

UNLABELLED: At an ISUP (International Society of Urological Pathology) consensus conference in 2005 in San Antonio, Texas, the old Gleason grading system for prostatic carcinoma from 1966 underwent its first major revision. With this modified Grading system a shift of the most frequent Gleason scores from 6 to 7a (3+4) in biopsy specimens and an increased degree of agreement between specimens of biopsies and radical prostatectomies with carcinoma of the prostate could be demonstrated. After modified grading of GS 3+4=7a tumours 95% were stage pT2, while 79% of GS 4+3=7b tumours were stage pT3-4. In cases with PSA <10 ng/ml and tumour extent <20% the most frequent Gleason scores were 6 and 7a. Cases with serum PSA >10 ng/ml or tumour extent >20% had higher scores (7b or higher). Cancers with tumour infiltration of <1mm in one of 12 cores and PSA <10 ng/ml were mainly low grade (Gleason scores 6 and 7a) and may correspond to so called insignificant carcinoma of the prostate. CONCLUSION: With the modified Gleason system, grade, stage, tumour extent and serum PSA show good correlations and characterize the difference between low and high grade malignancy of prostate carcinoma.

Correlation of modified Gleason grading of prostate carcinoma with age, serum prostate specific antigen and tumor extent in needle biopsy specimens.

OBJECTIVE: To investigate the correlation of biopsy grade with age, serum prostate specific antigen (PSA) and biopsy tumor extent using the conventional and modified Gleason grading systems. STUDY DESIGN: A total of 828 consecutive needle biopsy specimens of prostate carcinoma were collected from the years 1995 and 2000 (graded with conventional Gleason grading) and 2006 and 2007 (graded with modified Gleason grading). RESULTS: Both conventional and modified Gleason grading correlated with age, serum PSA, percent positive biopsies and percent cancer length. In 2006-2007, the patients were on average younger and more biopsy cores were taken per patient. Serum PSA and percent positive cores were lower than in the 1995 and 2000 group, indicating a stage shift downward, but the Gleason scores were nevertheless higher. CONCLUSION: Conventional and modified Gleason grading both correlated with age, serum PSA and cancer involvement in needle biopsies. With modified Gleason grading there is a grade shift upward despite the downstaging that has been observed in recent years.

Correlation of modified Gleason grading with pT stage of prostatic carcinoma after radical prostatectomy.

OBJECTIVE: To study the correlation between modified Gleason score (GS) and pT stage of radical prostatectomy (RP) specimens. STUDY DESIGN: Six hundred forty-nine consecutive RP specimens were graded according to the conventional and the modified Gleason grading systems. RESULTS: A total of 29% of the tumors were upgraded. Both variants of GS correlated with pathologic stage. Stage pT2 tumors were assigned a GS of 3-6 less often with modified grading than with conventional grading (29% and 84%, respectively). The only significant difference of stage distribution between conventional and modified GS was for GS 7, where pT2 was the most common stage with modified grading (54%) and pT3 was most common with conventional grading (67%). Of GS 3 + 4 = 7a tumors, 95% were stage pT2, while 79% of GS 4 + 3 = 7b tumors were stage pT3-4. CONCLUSION: The stage distribution of modified GSs of RP specimens differs from that of conventional GSs, but a good correlation exists between grade and pT stage. Notably, GS 4 + 3 = 7b was more often associated with high stage than was GS 3 + 4 = 7a.

Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract.

AIM: Inverted papilloma (IP) of the urinary tract can be difficult to distinguish from noninvasive urothelial carcinoma with prominent inverted growth pattern (invNIUC). Ancillary markers may help to resolve such cases and clarify the reported malignant potential of some IPs. METHODS: Eighty-nine urothelial lesions initially diagnosed as IP were reviewed by 4 experienced urologic pathologists and studied immunohistochemically (Ki67, p53, CK20, MSH2, MLH1, and MSH6). Mutations of the FGFR3 gene, deletions (loss of heterozygosity) of 9p, 9q, and 17p, microsatellite instability, and elevated microsatellite instability at selected tetranucleotides were also analyzed. RESULTS: Considerable interobserver variability in histopathologic diagnoses was noticed. Only 62 (69.7%) initial diagnoses were confirmed by the review pathologists whereas 23 tumors (25.8%) were redefined as invNIUC. Molecular analyses revealed infrequent alterations in IPs, including microsatellite instability (1.8%), elevated microsatellite instability at selected tetranucleotides (13.2%), FGFR3 mutations (9.8%), 9p deletions (3.9%), 9q deletions (13.2%), 17p deletions (5.1%), nuclear p53 accumulation (18.9%), and aberrant immunostaining for MSH2 (5.8%), MLH1 (11.8%), and MSH6 (3.8%). IP and invNIUC differed in FGFR3 mutations and Ki-67 labeling index (P<0.001 each), and 9q loss of heterozygosity (P=0.03). There were fewer recurrences in IP (5.4%) compared with invNIUC (40.9%; P<0.0001). CONCLUSIONS: IP is a benign lesion that lacks specific genetic alterations found in exophytic noninvasive papillary urothelial tumors. These lesions could be reactive in nature, perhaps secondary to chronic inflammation or a neoplastic process that lack specific genetic alterations. Nevertheless given the clinical and molecular data of this study a conservative clinical approach is appropriate.

The significance of modified Gleason grading of prostatic carcinoma in biopsy and radical prostatectomy specimens.

At an International Society of Urological Pathology consensus conference in 2005, the Gleason grading system for prostatic carcinoma underwent its first major revision. Gleason pattern 4 now includes most cribriform patterns and also fused and poorly formed glands. Our aims were to compare the grade distributions and assess the agreement between biopsy and radical prostatectomy specimens for the modified and conventional Gleason grading. More than 3,000 radical prostatectomy (RP), needle biopsies (NB) and transurethral resection specimens were assigned modified Gleason score (GS). In NB, modified GS 3 + 3 = 6 and 3 + 4 = 7a were almost equally common, while in RP, 3 + 4 = 7a was most common followed by 4 + 3 = 7b. After application of the modified GS on NB, a substantial shift in GS distribution occurred: The proportion of GS 6 and 7 were 48 and 26%, respectively, with conventional Gleason grading as compared to 22 and 68%, respectively, with modified grading. In 368 men, the agreement between NB and RP with a modified GS 6, 7a, 7b and 8-10 in NB was 28, 88, 68 and 64-100%, respectively. The overall agreement improved from 58 to 72% (p < 0.001) compared to conventional GS. The higher agreement with modified Gleason grading may facilitate therapeutic decisions.

Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer.

BACKGROUND: In spite of excellent cure rates for prostate cancer patients with favorable tumor characteristics, patients with unfavorable characteristics after radical prostatectomy are still at a significantly increased risk of tumor progression. Early adjuvant hormonal therapy (AHT) has been shown to be of prognostic benefit in these patients. Unfortunately initiation and duration of early AHT in the individual patient is based on statistic data. PSA, as the standard prostate marker is neither able to reliably indicate minimal residual tumor disease in the early postoperative phase, nor can it be used for therapy monitoring due to the suppressive effect of hormonal therapy on PSA production. Promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1-HM) has been shown to be the most common DNA alteration of primary prostatic carcinoma which, when used as a marker, is supposed to be able to overcome some of the disadvantages of PSA. However until now information on the impact of hormonal therapy on the detection of GSTP1-HM is lacking. The purpose of our study was to assess the impact of endocrine therapy on the detection of GSTP1-HM by methylation-specific PCR (MSP) in prostate cancer. METHODS: Paraffin embedded tumor samples from the radical prostatectomy (RP) specimens from 15 patients after hormonal therapy (HT) (mean 8 months) were assessed by MSP. In 8 of the patients the GSTP-1 status of the tumors before HT was assessed on the corresponding initial diagnostic biopsies. RESULTS: Following HT MSP showed GSTP1-HM in 13/15 of the RP specimens. In two patients analysis of the RP specimens failed to show GSTP1-HM. All initial tumor samples (8/8 biopsy specimens) showed GSTP1-HM, including both patients negative for GSTP1 HM in the corresponding RP specimen. CONCLUSION: In most cases hormonal therapy appears to not alter GSTP1 HM detection. However the change from a positive to a negative GSTP1 HM status in a subset of the patients may point to an, at least partial androgen dependency. Further studies on a larger cohort of patients are necessary to assess its frequency and the exact hormonal interactions.

The significance of the P504S expression pattern of high-grade prostatic intraepithelial neoplasia (HGPIN) with and without adenocarcinoma of the prostate in biopsy and radical prostatectomy specimens.

Diagnosis of prostatic adenocarcinoma is usually not difficult in biopsy specimens. Problems may occur in biopsy specimens, containing only a few suspicious lesions. Recently, P504S has been tested as a new marker for prostatic carcinoma. When over-expressed in atypical glands without basal cells, it establishes the diagnosis of prostatic carcinoma. We analysed the staining intensity of P504S in 208 biopsy specimens from prostates (1) with adenocarcinoma (n=132), (2) with high-grade prostatic intraepithelial neoplasia (HGPIN) with adenocarcinoma (n=36), (3) with HGPIN alone (n=40) and in radical prostatectomy specimens with HGPIN adjacent to (n=54) or distant from adenocarcinoma (n=64). P504S expression was negative to weakly positive in biopsy specimens showing HGPIN without carcinoma and weakly positive in radical prostatectomy specimens revealing HGPIN distant from adenocarcinoma. In biopsy specimens with a combination of HGPIN and adenocarcinoma and in radical prostatectomy specimens with HGPIN adjacent to adenocarcinoma, P504S was strongly expressed. The same findings were made in radical prostatectomy specimens containing adenocarcinoma and HGPIN adjacent to or distant from adenocarcinoma and in preoperative biopsies revealing adenocarcinoma and HGPIN. These results suggest that moderate to strong P504S expression in HGPIN of biopsy specimens is indicative of an associated adenocarcinoma and may be helpful in the choice of therapy.

Prognosis of stage pT0 after prolonged neoadjuvant endocrine therapy of prostate cancer: a matched-pair analysis.

OBJECTIVES: Stage pT0 following prolonged neoadjuvant endocrine therapy (PPNET) of prostate cancer is of great clinical interest, because this finding suggests maximum tumor damage. Therefore pT0 patients are expected to have an extremely favorable PSA progression rate. The purpose of this study was to assess whether the PSA progression rate of pT0 patients after PPNET is lower than that of non-pT0 patients after PPNET. METHODS: 174 patients with previously untreated, clinical stage cT1-3 carcinomas were submitted to PSA monitored complete androgen deprivation therapy followed by radical prostatectomy (RP). In 138 patients the RP specimens showed residual cancer, in 36 patients no residual cancer was found. Biochemical progression was defined as PSA >/=0.2ng/ml. To control for confounding prognostic factors (Gleason score, cT-stage) between both groups a matched-pair analysis for the cumulative risk of biochemical failure was performed, resulting in 30 matched pairs. RESULTS: With a median follow-up of 37.9 and 46.0 months in the matched non-pT0 and pT0 cohort respectively, matched-pair analysis failed to demonstrate significant differences in crude PSA relapse-free survival between both groups (p=0.7758). CONCLUSION: The results suggest that patients converted into pT0 after PPNET do not represent a subgroup with an extremely favorable prognosis. However our results have to be confirmed by the assessment of larger cohorts of pT0 patients with a longer follow-up. The presented data do not allow drawing any conclusions on the prognostic impact of PPNET in general.

Methylation-specific PCR for DNA-based detection of occult tumor cells in lymph nodes of prostate cancer patients.

OBJECTIVES: To assess the feasibility of methylation-specific PCR (MSP) for the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer cells in lymph nodes (LNs). METHODS: Paraffin-embedded pelvic LNs from 20 patients with pT2pN0M0R0 prostate cancer who developed PSA relapse were assessed by MSP. In 18 of the patients, samples of the primary tumor were obtained for MSP. In 19 patients, bone marrow (BM) aspirates were analyzed preoperatively for disseminated tumor cells by immunocytochemistry (mAb A45-B/B3). In 16 patients, biopsies of the anastomotic region were performed following PSA relapse. As a negative control GSTP1 methylation status was also assessed in LNs from 9 patients for whom an autopsy was performed for non-cancer-related causes. RESULTS: All primary tumors displayed GSTP1 hypermethylation (HM). Preoperative BM assessment showed disseminated tumor cells in 8/20 cases (40%). In 4 patients, biopsies of the vesico-urethral anastomosis showed local tumor recurrence. The LNs in the cancer patients showed GSTP1 HM in 18/20 cases (90%) versus 1/9 patients (11.1%) in the non-cancer cohort (p<0.0001). CONCLUSION: GSTP1 HM appears to be well suited for molecular staging of prostate cancer and accurately detects disseminated tumor cells in LNs, which was seen in 90% of the patients with PSA relapse. However, the limited number of patients and the finding of benign and malignant prostatic tissue at the vesico-urethral anastomosis as a putative local source of PSA recurrence does not allow us to draw conclusions on the prognostic significance of our findings, yet.

Follow-up of nondetectable prostate carcinoma (pT0) after prolonged PSA-monitored neoadjuvant hormonal therapy followed by radical prostatectomy.

OBJECTIVES: To test the hypothesis that in patients with Stage pT0 after prolonged prostate-specific antigen (PSA)-monitored neoadjuvant endocrine therapy, biochemical relapse is extremely rare and derives from systemic tumor recurrence. METHODS: A total of 227 patients with Stage cT1-3 carcinoma underwent PSA-monitored prolonged neoadjuvant endocrine treatment followed by radical prostatectomy. In all pT0 patients, PSA follow-up data were obtained. Patients with a PSA relapse (0.2 ng/mL or greater) underwent biopsy from the vesicourethral anastomosis, and some underwent radiotherapy. RESULTS: Stage pT0 was diagnosed in 38 (16.7%) of 227 patients. The pT0 rate in those with cT1, cT2, and cT3 cancer was 28.2% (11 of 39), 26.3% (20 of 76), and 6.25% (7 of 112), respectively. In Gleason score 2 to 4, 5 to 6, and 7 to 10 carcinoma, the pT0 rate was 50% (3 of 6), 28.4% (25 of 88), and 7.1% (9 of 126), respectively. The median follow-up was 47.0 months (range 20 to 180). PSA relapse was seen in 7 (18.4%) of 38 patients. PSA relapse derived from local tumor relapse in 2 cases, local and systemic tumor relapse in 1 case, and local benign prostate glands in 2 cases. In 2 cases, the nature of the PSA relapse remained unknown. CONCLUSIONS: Mainly clinically organ-confined, low and intermediate-grade tumors were converted to Stage pT0. Local PSA relapse was surprisingly frequent. In part, its malignant nature was confirmed histologically. However, the finding of residual benign prostate glands shows that PSA relapse does not always correspond with tumor relapse. Whether the prognosis in pT0 patients is significantly improved compared with nonpretreated patients cannot be answered on the basis of our data. Nevertheless, the presented results were disappointing.

Molecular pathology of non-invasive urothelial carcinomas (part I).

An international consultation on the diagnosis of non-invasive urothelial neoplasms was held in Ancona, Italy in May 2001. Besides histology and problems of classification, one group of experts (Committee no. 3) discussed the molecular pathology and cytometry of non-invasive urothelial carcinomas. In the following first part, special immunohistochemical and molecular markers for stratifications in bladder cancer were discussed including different cytokeratins (clone 34betaE12, CK 20), cell proliferation markers (Ki67/MIB-1, PCNA, AgNOR, DNA-cytometry), tumor suppressor genes and oncogenes (p53, p21, erb-B2, bcl-2), different receptor expressions of epidermal growth factor and vascular endothelial growth factor and others. These molecular markers were analyzed in diagnosis of urothelial carcinomas, recurrences, progression and response to treatment.

Nonepithelial tumor-like lesions of the prostate: a never-ending diagnostic problem.

Nonepithelial tumor-like lesions of the prostate include benign prostatic hyperplasia-associated stromal nodules, postoperative spindle cell nodules, benign mesenchymal tumors and sarcomas. These lesions and neoplasms are rare but need to be exactly classified for adequate treatment. This review focuses on the differential diagnosis between the various benign and malignant entities and compares the new WHO classification with a recently published typing of prostatic stromal lesions of unknown malignant potential.

Fundamentals on the pathology of prostatic carcinoma after brachytherapy.

Morphologic analyses of radical prostatectomy specimens after brachytherapy are rarities, as only few patients undergo radical prostatectomy due to prostate-specific antigen (PSA) progress after brachytherapy. In the literature, there are merely sporadic reports that do essentially correspond to findings after conventional radiotherapy with regressive changes in the tumor glands and, especially, in the surrounding stroma. From the presented cases, it can be concluded that the seed density must be very high in order to prevent tumor progression through undamaged parts of the carcinoma. The sequels of brachytherapy are compared with the reactions of prostatic carcinomas to various modes of therapy. It is demonstrated what the clinician can expect and which modes of control exist at present.