Prostate-specific antigen adjusted for the transition zone volume versus free-to-total prostate-specific antigen ratio in predicting prostate cancer

BACKGROUND: We performed this study to assess the efficacy of prostate-specific antigen adjusted for the transition zone volume (PSATZ) and free-to-total prostate-specific antigen (PSA) ratio (F/T ratio) in predicting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. METHODS: Between March 1997 and September 1998, PSATZ was obtained from 67 patients who underwent ultrasonography guided systemic sextant biopsies and had a PSA of 4.1-10.0 ng/mL. PSATZ was compared with F/T ratio via receiver operating characteristic (ROC) curves. RESULTS: Of 67 patients, 22 (32.8%) had prostate cancer and 45 (67.2%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSA density, F/T ratio and PSATZ were 7.96+/-2.01ng/mL, 0.28+/-0.14 ng/mL/cc, 0.10+/-0.06 and 0.70+/-0.28 ng/mL/cc in patients with prostate cancer and 6.39+/-1.68 ng/mL, 0.16+/-0.06 ng/mL/cc, 0.15+/-0.05 and 0.29+/-0.10 ng/mL/cc in patients with BPH, respectively. The ROC curve analysis demonstrated that PSATZ predicted the biopsy outcome significantly better than F/T ratio in all 67 patients (P<0.01) and in a subset of 53 men with normal digital rectal examination (P<0.01). With a cut-off value of 0.35 ng/mL/cc, PSATZ had a sensitivity of 86% and a specificity of 89% for predicting prostate cancer. CONCLUSIONS: These results suggest that PSATZ and F/T ratio may be useful in diagnosing prostate cancer with intermediate levels of PSA. Prostate-specific antigen adjusted for the transition zone volume is more accurate than F/T ratio in distinguishing benign prostatic disease from prostate cancer. But large prospective studies are required to assess the precise role of PSATZ and F/T ratio in early prostate cancer detection.     

Using multiple cutpoints for the free-to-total prostate specific antigen ratio improves the accuracy of prostate cancer detection

BACKGROUND: Using a single cutpoint for the free-to-total (F/T) prostate specific antigen (PSA) ratio loses important diagnostic information. We evaluated the performance of multiple F/T PSA cutpoints in detecting prostate cancer in men with nonspecific PSA values. METHODS: We extracted sensitivity and specificity data from 12 studies reporting on >or=30 cancer patients with PSA values between 2.0 and 10.0 ng/mL. We calculated stratum-specific likelihood ratios (LR) and areas under the receiver operating characteristic (ROC) curves. RESULTS: Multiple cutpoints for the F/T PSA ratio significantly increased the area under the ROC (0.70) compared with the single investigator-selected cutpoint (0.62), P < 0.004. The LR for the most positive cutpoint stratum (2.62) was significantly higher than the LR for a positive test from the single cutpoint (1.36), P < 0.004. CONCLUSIONS: Using multiple cutpoints increased the discriminating power of the F/T PSA ratio and led to greater probability revisions in the most positive test-result strata.     

Effect of prostatic biopsy on free-to-total prostate-specific antigen ratio in patients with prostate cancer

BACKGROUND: We determined the effect of prostatic biopsy on the changes in total and free prostate-specific antigen (PSA) and free-to-total PSA ratio (F/T ratio) and examined if there are differences in these parameters between patients with benign and malignant histologic findings. METHODS: The concentration of total and free PSA and the F/T ratio were determined in 35 men before and 1 h after prostatic biopsy. The level of PSA was measured with a chemiluminescent enzyme assay. Of 35 patients, nine were diagnosed as having prostate cancer. RESULTS: In patients whose biopsy revealed cancer, the F/T ratio was lower than those without cancer, although there were no differences in total and free PSA value before prostatic biopsy. One hour after prostatic biopsy, there was an increase in the level of total and free PSA and the F/T ratio in all men. The increase in the F/T ratio was greater in patients whose biopsies revealed no prostate cancer. In patients with stage B cancer, these parameters increased more than those with stage C/D cancer. CONCLUSION: Prostatic biopsy causes a dramatic increase in total and free PSA. The F/T ratio also increased after biopsy. The PSA response to prostatic biopsy might be different in patients with and without prostatic malignancy. The response might also be different according to stage of prostate cancer.     

Early diagnosis of prostate cancer using free／total prostate specific antigen ratio： a population based screening data

Aim: To evaluate the use of free/total prostate specific antig enratio (fPSA/tPSA ratio) in improving the early diagnosis of prostate cancer. Methods: The fPSA/tPSA ratio in the serum was analyzed in 187 men with tPSA ranging between 4.0 and 20.0μg/L. Allof them underwent ultrasound guided sextant prostatic biopsy.The results were calculated by SPSS 10.0 software.     

Second to fourth digit ratio: a predictor of prostate‐specific antigen level and the presence of prostate cancer

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The Homeobox genes, Hox a and d, control urinogenital system differentiation and digit development. The patterns of digit formation may be related to gonad function and may be reflected in 2nd to 4th digit ratio (digit ratio). Digit ratio is negatively correlated with prenatal testosterone levels and androgen receptor activity which is related to the increased prostate cancer risk. Patients with a lower digit ratio have a higher risk of prostate biopsy due to high PSA level, and of prostate cancer. Digit ratio could be a predictor of high PSA level and the presence of prostate cancer.

OBJECTIVE

To investigate the relationships between the 2nd to 4th digit ratio (digit ratio) and prostate volume, prostate‐specific antigen (PSA) level, and the presence of prostate cancer.

PATIENTS AND METHODS

Of the men that presented with lower urinary tract symptoms (LUTS) at a single tertiary academic center, 366 men aged 40 or older with a PSA level ≤40 ng/mL were prospectively enrolled. Right‐hand 2nd and 4th digit lengths were measured prior to the PSA determinations and transrectal ultrasonography (TRUS). Prostate volumes were measured by TRUS without information about digit length. Patients with a PSA level ≥3 ng/mL underwent prostate biopsy.

RESULTS

No relationship was found between prostate volume and digit ratio [correlation coefficient (r) =?0.038, P= 0.466]. But, significant negative correlations were found between digit ratio and PSA (r=?0.140, P= 0.007). When the patients were divided into two groups (Group A: digit ratio <0.95, n= 184; Group B: digit ratio ≥0.95, n= 182), Group A had a higher mean PSA level than Group B (3.26 ± 5.54 ng/mL vs 1.89 ± 2.24 ng/mL, P= 0.002) and had significantly higher risks of prostate biopsy [odds ratio (OR) = 1.75, 95% CI = 1.07–2.84] and prostate cancer (OR = 3.22, 95% CI = 1.33–7.78).

CONCLUSIONS

Patients with a lower digit ratio have higher risks of prostate biopsy and prostate cancer.     

The distribution of serum prostate-specific antigen levels among American men: implications for prostate cancer prevalence and screening

BACKGROUND: The purpose of this study was to describe the distribution of serum prostate-specific antigen (PSA) among American men and to estimate the number of prevalent cases of biopsy detectable prostate cancer among men with normal serum PSA. METHODS: We analyzed data of the National Health and Nutrition Examination Survey 2001-2002 (NHANES 2001-2002) data and combined these results with published data from the Prostate Cancer Prevention Trial (PCPT). RESULTS: Most men in the US have a serum PSA < or = 4.0 ng/ml, and mean and median serum PSA values rise steadily with age. There are an estimated 1,607,585 (95% CI 1,370,848-1,844,322) prevalent cases of biopsy detectable prostate cancer in men aged 62-85 years with a serum PSA < or = 4 ng/ml. Among men aged 62-75 years, there are an estimated 1,252,143 (95% CI 1,054,677-1,449,609) prevalent cases, including an estimated 195,499 (95% CI 140,234-250,764) high-grade tumors. CONCLUSION: A large number of prevalent cases of biopsy detectable prostate cancer exist in American men with a normal PSA.     

Polymorphisms in the androgen receptor and the prostate-specific antigen genes and prostate cancer risk

BACKGROUND: Prostate cancer (PCa) is an androgen-dependent disease. Polymorphic CAG and GGC microsatellites in the androgen receptor (AR) can alter transactivation of androgen-responsive genes in in vitro studies. Potentially, this may influence PCa risk. METHODS: Germline DNA samples and survey data were collected from 591 newly diagnosed PCa cases and 538 population-based controls of similar age (40-64 years), from King County, WA. Odds ratios (ORs) and 95% confidence limits were estimated using logistic regression models. RESULTS: No association was detected between PCa and having <22 versus > or =22 CAG repeats (OR = 1.1; 95% CI 0.9, 1.4) or < or =16 GGC versus >16 GGC repeats (OR = 1.0; 95% CI 0.9, 1.4). These findings were unchanged after controlling for body mass index or family history of PCa. No clear relation was detected between APS -158 G/A genotype and risk of PCa or serum prostate-specific antigen (PSA) levels. These findings did not differ by stage or grade of PCa. CONCLUSIONS: We found no evidence that risk of PCa is associated with the AR CAG, GGC, or PSA-158 AREI genetic polymorphisms in middle-aged Caucasian men.     

Combined tests of prostate specific antigen and testosterone will improve diagnosis and monitoring the progression of prostate cancer

Prostate-specific antigen (PSA) testing has been widely used to screen men for prostate cancer (PCa) and to monitor PCa progression. However, more studies have shown that around 15% of men with low or normal PSA levels have PCa. In this study, we aimed to investigate the relationship of androgen and PSA levels and to better understand the reason that some PCa patients have low serum PSA values. The in vitro data demonstrated that cultured LNCaP cells ceased to produce PSA after androgen withdrawal and resumed PSA production after androgen was re-added. The in vivo experiment results showed that 48% of PCa xenografts carrying mice have serum PSA level lower than 4 ng ml⁻¹. The serum PSA levels increased significantly with rises in testosterone (T) levels 1 week after T pellet implantation. These data indicated that the androgen is a key factor controlling the production of PSA. Low serum PSA levels in mice with PCa xenografts are associated with low serum T levels. Raising serum T levels in tumor caring mice will also significantly increase serum PSA level. This may have clinical implications when screening PSA in men, who have occult PCa.     

Effect of intra-observer variation in prostate volume measurement on prostate-specific antigen density calculations among prostate cancer active surveillance participants

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The Epstein criteria, which utilize prostate specific antigen density (PSAD) benchmarks, are recognized to be a reasonable method of selecting men for active surveillance of prostate cancer. Transrectal ultrasonography, however, may not be a sufficiently precise method of measuring prostate volume for the determination of PSAD. This study shows that despite impressive intra‐observer variability in transrectal ultrasonography guided prostate volume measurements, this variability typically does not affect the PSAD to an extent by which qualification for active surveillance would be altered.

OBJECTIVE

? To determine intra‐observer variability in transrectal ultrasonography (TRUS) guided prostate volume measurements in the Johns Hopkins active surveillance group and to establish whether or not this variability could affect prostate‐specific antigen density (PSAD) estimates in this cohort.

PATIENTS AND METHODS

? In all, 253 patients with a combined total of 1111 prostate biopsies underwent TRUS‐guided prostate volume measurements performed by the same physician at least three times over the course of their care. ? Coefficients of variation (CV) were calculated for each set of measurements performed on each patient by the same physician, and average CVs were determined for each physician and for physicians overall. The CVs were correlated with the average of each patient’s measured prostate volumes to look for any trend. ? Finally, measured prostate volumes were used with each patient’s initial prostate‐specific antigen (PSA) value to calculate PSAD to reveal whether or not the degree of variability found in these measurements would have led to PSADs that would have otherwise precluded qualification for active surveillance.

RESULTS

? The average CV for all sets of prostate volume data was 0.168. Average CVs for each physician ranged from 0.136 to 0.234. ? However, actual CVs ranged anywhere from 0.013 to 0.549. The CVs were found to have no correlation with prostate volumes (Pearson correlation coefficient: 0.04). ? In 95% of cases, variability in TRUS‐guided prostate volume measurement did not affect PSAD sufficiently to elicit a value greater than 0.15.

CONCLUSIONS

? Even among individuals who are highly experienced in TRUS‐guided prostate volume measurement, significant intra‐observer variation exists. However, this variability is not enough to affect one’s eligibility for prostate cancer active surveillance when PSAD criteria are used. ? The TRUS‐guided prostate volume measurements remain a reliable method of assessing PSAD in patients with prostate cancer.     

不同治疗方案与局部晚期前列腺癌患者前列腺特异性抗原进展及生存状况的Meta分析

目的 应用Meta分析探讨不同治疗方案对局部晚期前列腺癌前列腺特异性抗原(PSA)进展及生存状况的影响. 方法制订原始文献的纳入标准、剔除标准及检索策略.以优势比(OR)及其95%可信区间(95%CI)为效应尺度,应用Meta分析固定效应模型和随机效应模型对有关治疗局部晚期前列腺癌不同方案的纳入文献进行综合定量评价. 结果 符合纳入标准的8篇文献进入Meta分析,共3826例.5篇为前列腺根治性切除术(RP)联合辅助治疗与单纯用RP或不用RP进行比较,以PSA进展率为评价指标,合并后的OR值为0.86,95%CI为0.48～1.56;3篇为RP联合激素治疗与单纯用RP或不用RP进行比较,以疾病特异性死亡率为评价指标,合并后的OR值为0.72,95%CJ为0.51～1.02. 结论 RP联合辅助治疗可以显著减少局部晚期前列腺癌患者术后PSA进展,对疾病特异性死亡率却无显著影响.     

Preoperative prediction of final pathological features is not improved by the free-to-total prostate-specific antigen ratio in Japanese men with clinically localized prostate cancer

BACKGROUND: The objective of the present study was to determine whether the percentage of free/total prostate-specific antigen (f/tPSA) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can preoperatively predict organ-confined versus extraprostatic disease. METHODS: Serum levels of fPSA and tPSA were measured in 97 patients with clinically organ-confined disease before they underwent radical prostatectomy. The relationships of tPSA, f/tPSA and the pathological stage of the prostatectomy specimens were analyzed. Furthermore, the ability of f/tPSA to predict the pathological features was compared with those of tPSA and systematic biopsy findings. RESULTS: Organ-confined and extraprostatic extension diseases were present in 51 and 46 men, respectively. tPSA in patients with extraprostatic diseases was significantly higher than that in those with organ-confined diseases; however, there was no significant difference in f/tPSA between these two groups. There was also a significant difference in tPSA levels at each pathological stage, while f/tPSA did not parallel the pathological stage. Furthermore, there was no additional information concerning the extent of prostate cancer obtained when f/tPSA was combined with tPSA or with the percent of positive biopsy cores, which is the most significant predictor of the extent of prostate cancer among factors associated with systematic biopsy. CONCLUSION: f/tPSA could not predict the final pathological features in patients with clinically localized prostate cancer before radical prostatectomy. Moreover, the predictive value provided by tPSA or systematic biopsy findings was not improved by combined analysis with f/tPSA.     

Population-based screening for prostate cancer by measuring total serum prostate-specific antigen in Iran

OBJECTIVE: To report the results from an Iranian large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer. MATERIALS AND METHODS: A total of 3758 Iranian men older than 40 years were mass checked by PSA-based screening. Men with an abnormal digital rectal examination (DRE) and serum total PSA level of greater than 4 ng/mL, underwent transrectal ultrasonography (TRUS)-guided extended prostate biopsy. RESULTS: The PSA value (mean +/- standard deviation, SD) in all men without prostate cancer was 1.6 +/- 1.1 ng/mL and in those with cancer 18 +/- 44.8 ng/mL (P = 0.001). PSA values increased with age. In those aged 40-49, 50-59, 60-69 and > or = 70 years, the mean +/- SD PSA values were 1.3 +/- 0.7, 1.4 +/- 0.8, 1.8 +/- 1 and 2.2 +/- 1.6 ng/mL, respectively. Among the screened men, 323 (8.6%) had a serum PSA concentration greater than 4 ng/mL. Of patients who underwent prostate biopsy (230, 71.2%), 129 (positive predictive value, 56.1%) had prostate cancer. Additionally, nine cancers were detected among 16 patients with PSA of less than 4 ng/mL who had a doubtful DRE finding. The overall cancer detection rate was 3.6%; 1.4% at 40-49, 1.6% at 50-59, 4.2% at 60-69 and 12.9% at >/=70 years. Conventional systematic sextant biopsies, which accounted for six of the 10 cores in our biopsy scheme, detected 98 (71%) of the cancers. CONCLUSIONS: The Iranian male population develops prostate cancer quite commonly if their serum PSA levels are greater than 4.0 ng/mL. In this study, 65.9% of the detected cancers were clinically significant. The conventional systematic sextant technique may be inappropriate for detection of all prostate cancers. The results need to be confirmed in other randomized trials.     

Prostate‐specific antigen kinetics in localized and advanced prostate cancer

The successful management of prostate cancer requires early detection, appropriate risk assessment and optimum treatment. To this end, much research has been conducted over many years with the goal of identifying a reliable and easily measurable tumour marker that could be used on a large scale for the diagnosis, staging and monitoring of the disease. Prostate‐specific antigen (PSA) was independently discovered by two groups in the 1960s and 1970s, in semen and prostate tissue, and given different names. It later became evident that these proteins were encoded by the same gene and were the same protein. PSA was then identified as a useful marker for assessing patients with prostate cancer during their follow‐up. In 1986, PSA was approved by the United States Food and Drug Administration to monitor prostate cancer, and in 1994 approved as a tool for detecting the disease in men aged ≥50 years. PSA is now the most widely used serum marker for detecting and monitoring prostate cancer, but its use as a diagnostic marker is controversial because it has several limitations, including its low specificity (PSA levels are also increased in benign prostatic hyperplasia, and in general inflammatory responses) and low sensitivity. Furthermore, PSA levels are highly variable over time, and PSA poorly distinguishes indolent from aggressive cancers. As such, the use of PSA level as a diagnostic tool can lead to over‐detection of cancers that pose little threat to health and/or life. Moreover, the impact of PSA screening on prostate cancer mortality rates remains controversial, and will do so until the results of currently ongoing randomized controlled studies in Europe and the USA become available. To overcome the limitations of using PSA, research on PSA kinetics has developed considerably in the last decade. We review publications on the added value of PSA kinetics compared with single PSA measurements in the early detection of prostate cancer, and in predicting the outcome of patients with localized and advanced disease.     

F/T比值在前列腺癌筛选中的应用价值

目的：评价F／T比值在前列腺癌筛选中的作用。方法：运用直肠指检、B超、PSA、PSA密度（PSAD）、F／T比值对389例行健康体检的50岁以上男性进行前列腺癌筛选，并对各项方法的准确性、特异性、敏感性进行比较。结果：共检出前列腺癌15例，其中F／T比值在敏感性不降低的情况下，其特异性明显优于PSA和PSAD，特别是在PSA的诊断灰区能很好地将良、恶性病变区分开来，使将近50％的可疑患者免受活检。结论：F／T比值是前列腺癌筛选的有效手段。     

Concentration of enzymatically active prostate-specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models

BACKGROUND: Prostate-specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized. METHODS: The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC-82, LNCaP, LAPC-4) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor-bearing animals, was likewise assayed. RESULTS: Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600-2100 nM). The majority of this PSA is enzymatically active (i.e., 80-90%). Human PC-82 prostate cancer xenografts also have high concentrations of PSA in the ECF (624 +/- 360 nM), and the majority of this PSA is also enzymatically active (i.e., 66 +/- 4%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45 +/- 9 nM) and LAPC-4 (7.3 +/- 0.6 nM). Only a small portion of the total PSA isolated from DHT-containing, serum-free, conditioned media from these cell lines is enzymatically active (i.e., approximately 18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples. CONCLUSIONS: Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC-82 prostate cancer xenografts. In contrast, LNCaP and LAPC-4 human prostate cancer xenograft models secrete approximately 70-300-fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC-82, the most, optimized xenograft model for screening PSA targeted prodrugs.     

Usefulness of prostate-specific antigen velocity in screening for prostate cancer

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.     

Tumour markers for managing men who present with metastatic prostate cancer and serum prostate-specific antigen levels of <10 ng/mL

OBJECTIVE: To define immunohistochemical features of the primary cancers that might help in the differential diagnosis and monitoring of treatment in men presenting with metastatic prostate cancer and low serum levels of prostate-specific antigen (PSA), who can be difficult to diagnose and manage. PATIENTS AND METHODS: Paraffin blocks of prostate biopsies were obtained for 33 patients presenting with untreated metastatic prostate cancer and serum PSA levels of <10 ng/mL. Sections were immunostained for PSA, prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), androgen receptor (AR), chromogranin A and CD 56. RESULTS: The combined Gleason scores were 8-10 in 25 men (76%) and 6 or 7 in the other eight (24%). Morphologically, there were no neuroendocrine features. PSA immunostaining was equivocal in 12 (36%) cases and in a further 19 (58%) was strong but focal and could be missed on biopsy sampling. PSMA was expressed in 90% of cases, and staining was widely distributed in nine of the 12 in which PSA staining was equivocal. There was strong AR expression in 30 (91%) cases and it was present in areas where PSA was absent. CONCLUSION: In this patient group, immunohistochemical assessments of PSMA and AR are potentially useful as diagnostic markers.