Nomograms for the prediction of pathologic stage of clinically localized prostate cancer in Korean men

We analyzed the prostate cancer data of 317 Korean men with clinically localized prostate cancer who underwent radical prostatectomy at Asan Medical Center between June 1990 and November 2003 to construct nomograms predicting the pathologic stage of these tumors, and compared the outcome with preexisting nomograms. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node metastasis (LNM) using serum prostate-specific antigen (PSA), Gleason score and clinical stage. Nomograms representing percent probabilities were constructed and compared with those presented by Partin et al. by calculating areas under the receiver operating characteristics (ROC) curves. Median serum PSA at surgery was 10.8 ng/mL, and median biopsy Gleason score was 7. Overall OCD, ECE, SVI and LNM rates were 59.6%, 20.5%, 11.7% and 8.2%, respectively, and areas under the curves were 0.724, 0.626, 0.662, and 0.794, respectively. Pathologic stage of localized prostate cancer in Korean men may be predicted using the Partin table, with acceptable accuracy for OCD and LNM, but less so for ECE and SVI.     

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer.     

Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer.

Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart (TMPRSS2, ERG, ETV4) and one fusion (TMPRSS:ETV1) fluorescence in situ hybridization (FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2:ERG and TMPRSS2:ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2:ERG fusion, our assays allowed us to detect deletion of the 3' end of TMPRSS2 and the 5' end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P=0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5' and 3' partners may be involved in gene fusions in prostate cancer.     

The relative importance of anatomic and PSA factors to outcomes after radical prostatectomy for prostate cancer.

We report on how anatomic pathology observations and prostate-specific antigen (PSA) observations made before and just after radical prostatectomy relate to subsequent outcomes in men with prostate cancer. Our study patients consisted of more than 200 men who underwent radical prostatectomy and who had a mean follow-up of more than 6 years. We found that there were 2 categories of failures after surgery--one consisting of an eventual elevated PSA level and the other consisting of an early death from progressive tumor--and that these 2 failures related differently to PSA and anatomic pathology observations made at the time of prostatectomy. Whereas preoperative and postoperative levels of PSA related most closely to PSA failure, Gleason grade 5 and the percentage carcinoma related most closely to early death. Our results suggest how men could be sorted into 3 prognostic categories after surgery: one with high hazard for early death, a second with low hazard for early death but with high probability for eventual elevated PSA level, and a third with overall good prognosis.     

TMPRSS2-ERG融合基因在转移性前列腺癌中的表达

目的 检测转移性前列腺癌中TMPRSS2-ERG基因融合的发生率,探讨ERG基因重排在前列腺癌进展中的作用.方法 收集32例由细针穿刺诊断的转移性前列腺癌,穿刺部位包括盆腔及远处淋巴结、肝、骨、甲状腺等,回顾相关临床病理学资料.免疫组织化学采用EnVision法标记前列腺特异性抗原、突触素和嗜铬粒素A.运用ERG分离断...     

ERG gene rearrangement status in prostate cancer detected by immunohistochemistry

TMPRSS2-ERG, the most common gene fusion in prostate cancer, is associated with expression of a truncated protein product of the oncogene ERG. A novel anti-ERG monoclonal antibody has been recently characterized. We investigated the correlation between ERG rearrangement assessed by fluorescence in situ hybridization (FISH) and ERG expression detected by immunohistochemistry in a large cohort of patients treated with radical prostatectomy for clinically localized prostate cancer. Thirteen tissue microarrays comprising 305 tumors and a subset of 112 samples of nonneoplastic prostatic tissue were assessed for ERG rearrangement status by FISH and for ERG expression by immunohistochemistry. Accuracy of ERG detection by immunohistochemistry in predicting ERG status as assessed by FISH (criterion standard) was calculated in terms of sensitivity, specificity, positive and negative predictive values. Of 305 tumor foci, 103 (34%) showed ERG rearrangement by FISH. ERG was detected by immunohistochemistry in 100 (33%) cases, 99 of which were FISH positive. ERG detection by immunohistochemistry demonstrated a sensitivity and specificity of 96% and 99%, respectively, with positive and negative predictive values of 99% and 98%, respectively. None of the 112 samples of nonneoplastic prostatic tissue was rearranged by FISH or showed any ERG expression. In conclusion, ERG detection by immunohistochemistry in prostate cancer was highly predictive of ERG rearrangement as assessed by FISH in a large cohort of prostatectomy patients. Given the high yield and the easier task of performing immunohistochemistry vs. FISH, ERG assessment by immunohistochemistry may be useful for characterizing ERG status in prostate cancer.     

Nomogram for Prediction of Prostate Cancer with Serum Prostate Specific Antigen Less than 10 ng/mL

Although prostate-specific antigen (PSA) is a very useful screening tool, prostate biopsy is still necessary to confirm prostate cancer (PCA). However, it is reported that PSA is associated with a high false-positive rate and prostate biopsy also has various procedure-related complications. Therefore, the authors have devised a nomogram, which can be used to estimate the risk of PCA, using available clinical data for men with a serum PSA less than 10 ng/mL. Prostate biopsies were obtained from 2,139 patients from January 1998 to March 2011. Of them, 1,171 patients with a serum PSA less than 10 ng/mL were only included in this study. Patient age, PSA, free PSA, prostate volume, PSA density and percent free PSA ratio were analyzed. Among 1,171 patients, 255 patients (21.8%) were diagnosed as PCA. Multivariate analyses showed that patient age, prostate volume, PSA and percent free PSA had statistically significant relationships with PCA (P < 0.05) and were used as nomogram predictor variables. The area under the (ROC) curve for all factors in a model predicting PCA was 0.759 (95% CI, 0.716-0.803).

Graphical Abstract

相似文献   

Practice Patterns of Korean Urologists for Screening and Managing Prostate Cancer according to PSA Level

Purpose

There are still debates on the benefit of mass screening for prostate cancer (PCA) by prostate specific antigen (PSA) testing, and on systemized surveillance protocols according to PSA level. Furthermore, there is a paucity of literature on current practice patterns according to PSA level in the Korean urologic field. Here, we report the results of a nationwide, multicenter, retrospective chart-review study.

Materials and Methods

Overall 2122 Korean men (>40 years old, PSA >2.5 ng/mL) were included in our study (from 122 centers, in 2008). The primary endpoint was to analyze the rate of prostate biopsy according to PSA level. Secondary aims were to analyze the detection rate of PCA, the clinical features of patients, and the status of surveillance for PCA according to PSA level.

Results

The rate of prostate biopsy was 7.1%, 26.3%, 54.2%, and 64.3% according to PSA levels of 2.5-3.0, 3.0-4.0, 4.0-10.0, and >10.0 ng/mL, respectively, and the PCA detection rate was 16.0%, 22.2%, 20.2%, and 59.6%, respectively. At a PSA level >4.0 ng/mL, we found a lower incidence of prostate biopsy in local clinics than in general hospitals (21.6% vs. 66.2%, respectively). A significant proportion (16.6%) of patients exhibited high Gleason scores (≥8) even in the group with low PSA values (2.5-4.0 ng/mL).

Conclusion

We believe that the results from this nationwide study might provide an important database for the establishment of practical guidelines for the screening and management of PCA in Korean populations.     

Discrepancies between Gleason scores of needle biopsy and radical prostatectomy specimens

The purpose of this study was to determine the accuracy of Gleason scores in prostate needle biopsy diagnosis and to investigate factors affecting the accuracy of the tumor grade. A single pathologist reviewed 116 sets of prostate cancer biopsies and radical prostatectomy specimens. The following factors were examined to determine their effect on the accuracy of the biopsy Gleason scores: (i) relative tumor differentiation; (ii) pathological stage; (iii) amount of tissue in the biopsy specimen; (iv) amount of cancer tissue in the biopsy specimen; (v) tumor heterogeneity; (vi) clinical findings (prostate specific antigen value and digital rectal examination); and (vii) interobserver variability. In 53 cases the Gleason score of biopsy specimens was identical to the score of prostatectomy specimens (45.7%). Fifty-four cases (46.6%) of biopsy specimens were undergraded. The most common discrepancy was diagnosis of well-differentiated carcinoma in the biopsy but diagnosis of moderately differentiated tumor in the corresponding prostatectomy specimen. This discrepancy occurred when the amount of tumor in the biopsy was 3 mm or less. Biopsy and prostatectomy results showed less agreement when the original biopsy tumor grade rendered by nine different pathologists was used, suggesting that interobserver variability can adversely affect the accuracy of tumor grade. Clarifying the histologic criteria for distinguishing each grade, especially between Gleason grades 2 and 3, is important for accurate grading.     

Should each core with prostate cancer be assigned a separate gleason score?

If multiple biopsy cores contain prostate cancer with differing Gleason scores, should an overall Gleason score be assigned, or should each core be graded separately? We obtained data on 127 men with prostate cancer on needle biopsy who underwent subsequent radical prostatectomy at our institution. We compared the Gleason scores found on needle biopsy with the grade and stage (organ-confined, extra-prostatic extension, positive seminal vesicles or lymph nodes) at radical prostatectomy. On biopsy, 40 men had a pure Gleason score of 4 + 3 = 7, 25 men had a Gleason score of 4 + 3 = 7 with a Gleason score of 3 + 3 = 6 on a separate core of the biopsy specimen, 27 men had a pure Gleason score of 4 + 4 = 8, and 35 men had a Gleason score of 4 + 4 = 8 with separate cores containing Gleason pattern grade 3. A Gleason score of 4 + 4 = 8 with pattern grade 3 in other cores had a more advanced stage than a pure Gleason score of 4 + 3 = 7 (P = 0.008). There was no clear pattern analyzing pathological stage of men with a pure Gleason score of 4 + 3 = 7 in comparison with those with Gleason scores of 4 + 3 = 7 and 3 + 3 = 6 in other cores. The group with a Gleason score of 4 + 4 = 8 and Gleason pattern grade 3 on other cores had a higher overall grade on radical prostatectomy than the group with a pure Gleason score of 4 + 3 = 7 (P = 0.001). If one had assigned an overall Gleason score, then a biopsy with Gleason score 4 + 4 = 8 on 1 or more cores and some pattern grade 3 in other cores, would be designated as a Gleason score of 4 + 3 = 7. Based on our findings, patients with a Gleason score of 4 + 4 = 8 on one or more cores with pattern grade 3 in other cores should be given a final Gleason score of 4 + 4 = 8 instead of 4 + 3 = 7, because these patients are more likely to have higher stage and grade on radical prostatectomy, comparable to a pure Gleason score of 4 + 4 = 8. Each core should be assigned a separate Gleason score, especially in cases with high Gleason score cancer on at least 1 core.     

Active Surveillance des lokalisierten Prostatakarzinoms

Today, more than 80% of men diagnosed with prostate cancer (PCA) by PSA screening do not die from the sequelae of their disease. About 70% present with early, organ-confined cancer and almost half of them are small (<5 cm(3)) without evidence of progression over years (insignificant PCA). It is assumed that screening brings the diagnosis of PCA forward by about 9 years and that in almost one third of these cases immediate radical prostatectomy or radiotherapy would result in overtreatment. Thus, the treatment strategy of "active surveillance" with selective but delayed intervention for patients with organ-confined PCA could be an attractive alternative to the known curative therapy options. However, a prerequisite of such a therapeutic approach would be a precise identification of patients at high risk for cancer progression. Careful work-up of prostate core needle biopsies including improved pre-embedding preparation and detailed interpretation are of the utmost importance. A Gleason score 相似文献   

Carcinoma extent in prostate needle biopsy tissue in the prediction of whole gland tumor volume in a screening population

Increasing prostate tumor volume has been shown to correlate with numerous adverse prognostic indicators for patients with prostate carcinoma The ability to predict tumor volume from pretreatment parameters is potentially critical in the stratification of patients for different management strategies. We assessed the capacity of preoperative variables to predict tumor volume in 100 men diagnosed with prostate cancer in a prostate-specific antigen (PSA)-based screening program. Preoperative information included total serum PSA concentration and needle biopsy tissue variables, including Gleason score, number of positive cores, linear extent of carcinoma in millimeters, greatest percentage of carcinoma (in a single core), total percentage of carcinoma (all cores), presence of perineural invasion, and percentage of high-grade carcinoma. The postoperative end point was total tumor volume in radical prostatectomy tissue, calculated by image analysis. We determined independently significant factors and generated a predictive modelfor whole gland tumor volume. Total tumor volume was related significantly in multivariate analysis to 3 preoperative variables: linear extent of carcinoma, exponential number of positive cores, and serum PSA. A predictive model generated based on these 3 variables accounted for only 65% of the natural deviance of the data owing to data-point scatter for individual patients, suggesting that additional variables are needed to more accurately predict tumor volume. Findings highlight the importance of reporting quantitative measures of tumor amount in prostate needle biopsy specimens; several measures of tumor extent (vs 1 measure) provide maximal information on prostate cancer size.