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Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumour cells.

Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA- HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Immunological characterization and activity of transglutaminases in human normal and malignant prostate and in prostate cancer cell lines.

Using biochemical assays, we compared enzyme activities with the immunoreactivity of antibodies against rat seminal transglutaminase (TGase), human erythrocyte TGase and guinea pig liver TGase in human normal prostate, primary prostatic carcinomas and prostatic carcinoma cell lines. Glandular cells of the epithelium were only exceptionally positive with the antibody against (rat) secretory TGase. Using the antibodies against tissue-type TGase, most immunoreactive cells were found in the basal cell layer of prostatic epithelium as well as in stroma (fibroblasts, endothelial cells), whereas immunoreactive glandular cells were sparse. In the case of benign prostatic hyperplasia, few, irregularly distributed secretory cells along with a small number of stromal cells were also immunoreactive with the tissue-type TGase antibody. In dedifferentiated carcinomas, immunoreactive cells were nearly completely absent. Of the prostate cancer cell lines, the LNCaP line showed neither TGase enzyme activity nor immunoreactivity, whereas the PC-3 cell line displayed significant enzyme activity and immunoreactivity. No hormone-dependent changes in either enzyme activity or immunoreactivity were recorded after in vitro treatment of the respective cell lines with estrogens, androgens and antiandrogens. As there is no correlation between androgen deprivation and TGase expression in nonmalignant and malignant human prostatic epithelial cells, TGase activity more likely indicates cellular lesions and consecutive repair mechanisms.

Aged↗

Zinc concentration in human prostatic fluid: normal, chronic prostatitis, adenoma and cancer.

Radionuclide induced energy dispersive X-ray fluorescence was used to estimate zinc content in prostatic fluid in normal, chronic prostatitis, adenoma and cancer cases, Groups of patients suffering from chronic prostatitis, adenoma and malignant tumours consisting of 28, 28 and 13 men, respectively, were examined. The control group included 22 healthy volunteers. Expressed prostatic fluid was obtained by digital rectal massage. The zinc concentration of intact prostatic fluid was 590 +/- 45 (SE) micrograms/ml. Almost no difference was found between the zinc concentration for chronic prostatitis and for adenoma, and those for normal levels being 455 +/- 60 (SE) and 540 +/- 50 (SE) micrograms/ml, respectively. Prostatic neoplasm resulted in a significant decrease of zinc secretion, with the concentration averaging 34.7 +/- 9.6 micrograms/ml, p < 0.000001.

Adult↗

Proton MR spectroscopy of prostatic tissue focused on the detection of spermine, a possible biomarker of malignant behavior in prostate cancer.

To investigate whether polyamines may be valuable diagnostic and prognostic markers in prostate cancer, the presence of polyamines was studied in various human prostatic tissues using both proton magnetic resonance (MR) spectroscopy and high-pressure liquid chromatography (HPLC). The HPLC results showed that normal and benign hyperplastic prostatic tissues were characterized by a high content of spermine. Spermine levels were reduced in tumor tissue, especially in prostatic carcinoma with metastases, and in xenografts of human prostatic carcinoma cells. These preliminary results indicate that spermine may be used as a biomarker for malignant behavior. The MR spectroscopy study showed that it is possible to detect spermine resonances in prostatic biopsy material by one-dimensional and two-dimensional J-resolved MR spectroscopy at high field (600 MHz). Localized one-dimensional in vitro MR spectra obtained at the clinical field strength of 1.5 T showed spermine signals in the region between 3.0 and 3.3 ppm. In in vivo MR spectra of the human prostate, however, these signals were obscured by resonances of choline (3.2 ppm) and creatine (3.0 ppm).

Biomarkers, Tumor↗

Galectin-1 and galectin-3 expression in human prostate tissue and prostate cancer.

Galectin-1 and galectin-3, two beta-galactoside-binding proteins, have been suggested to play a role in the development and progression of cancer. We have studied the expression of these molecules in normal human prostate tissue and prostate adenocarcinoma. Immunohistochemistry was used to examine formalin-fixed, paraffin-embedded sections of seven normal human prostates, eight cases of prostatic intraepithelial neoplasia (PIN), 20 primary adenocarcinomas of the prostate, and 12 prostate cancer metastases. Galectin-1 was expressed in most cases of all four histologic types. In contrast, galectin-3 expression was significantly decreased in primary carcinoma and metastatic disease compared with normal and premalignant tissue. Galectin-3 expression in primary tumors tended to be less than that of surrounding normal glands. We conclude that loss of galectin-3 expression may be associated with the progression of prostate cancer.

Adenocarcinoma↗

Combination of signal intensity measurements of lesions in the peripheral zone of prostate with MRI and serum PSA level for differentiating benign disease from prostate cancer.

The aim of this study was to predict the benign or malignant nature of a prostatic lesion by defining a threshold value of signal intensity ratio and a limiting value of serum prostate-specific antigen (PSA) in patients with elevated PSA level. Twenty-six patients with elevated PSA level and no hypoechogenic lesions at endosonography underwent MR imaging using an endorectal body phased-array coil at 1.5 T (Siemens Magnetom Symphony). A T2-weighted turbo-spin-echo (TSE) pulse sequence was applied in a transverse orientation. Two radiologists evaluated the images. In the presence of a pathological finding they defined regions of interest (ROI) in the suspicious pathological area of the peripheral zone and in muscle for reference. The quotient of the two ROIs was calculated and then correlated with the actual PSA level. Diagnosis was confirmed by prostate biopsy. Ten of 12 patients with quotients smaller than 4 showed cancer at histology. Nine of 12 men with cancer proven by biopsy had PSA levels higher than 10 ng/ml. A significant difference (p < 0.001) was found between the quotients of cancer and quotients of chronic prostatitis, fibrosis, or glandular atrophy. The accuracy of tumor differentiation of the method was 77%. Measurement of signal intensity quotients in the peripheral zone of the prostate in combination with knowledge of defined limits of PSA levels the technique could be helpful in detecting additional cancer areas for prostate biopsy. False-negative tumor results of standard sextant biopsy can be reduced. In men with high PSA values the method has a role in differentiating between patients who require prostate biopsy and those of clinical observation.

Adult↗

Distribution of prostate carcinoma foci within the peripheral zone: analysis of 8,062 prostate biopsy cores.

The aim of this study was to evaluate the distribution of prostate cancer within the peripheral zone by prostate biopsies excluding the influence of the transition zone. A prospective, multicenter study was carried out using a consecutive series of men who underwent transrectal ultrasound guided prostate biopsies using different biopsy techniques at six institutions. Biopsies were directed strictly within the peripheral zone or strictly within the transition zone. A model of the peripheral zone with 18 sectors of similar volume was established and the biopsy cores obtained were associated with these sectors and analysed with respect to prostate cancer detection rate. A total of 904 men (mean age 66.8 years, range 42-86) with a median serum PSA of 8.1 ng/ml (2.2-940 ng/ml) entered the study. A total of 8,062 biopsy cores (mean 8.92/patient) were obtained. Each of the peripheral zone sectors tested by biopsies yielded a similar percentage of prostate cancer ( P=0.6). There was no increase in the incidence of cancer toward the lateral sectors compared to midline sectors ( P=0.53) of the peripheral zone. Biopsy sampling of the peripheral zone from the apex to the base yielded a similar percentage of prostate cancer ( P=0.47). Our data suggest that the distribution of cancer foci detected by biopsies in the peripheral zone of the prostate is homogeneous.

Adult↗

Prostatic fatty acids and cancer recurrence after radical prostatectomy for early-stage prostate cancer.

OBJECTIVE: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurrence following primary therapy. METHODS: Fatty acids were measured by capillary gas chromatography in fresh, non-cancerous prostate tissue collected from 184 men undergoing radical prostatectomy for clinically localized prostate cancer. Their association with risk of biochemical disease recurrence (a rising serum prostate-specific antigen following a disease-free [<0.1 ng/ml] interval > or =6 months) was analyzed using Cox proportional hazards models incorporating patient age, body mass index, tumor characteristics at diagnosis, and ethnicity. RESULTS: During an average follow-up of 48.7 months (median = 47), 14 patients experienced biochemical recurrence. Percent total polyunsaturated fatty acid and the ratio of oleic-to-stearic acid associated with risk (multivariable hazards ratio [HR] = 0.51, 95% confidence interval [CI] = 0.29 to 0.90, p = 0.021 and HR = 1.68, 95% CI = 1.21 to 2.33, p = 0.002, respectively, per 1 standard deviation increase). CONCLUSIONS: The results of this study are preliminary, but they suggest that pre-diagnostic prostatic concentrations of fatty acids associate with risk of biochemical recurrence following radical prostatectomy for clinically localized prostate cancer.

Black or African American↗

Soluble CD44 molecules in serum of patients with prostate cancer and benign prostatic hyperplasia.

Recent studies suggest that expression of CD44 splice variants are of prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exists between the concentration of soluble CD44 molecules in serum (CD44 standard form and CD44 splice variants v5 and v6) and the prostate cancer stage. Serum levels of these soluble CD44 isoforms were measured by ELISA tests specific for these proteins in controls (n = 30), patients with benign prostatic hyperplasia (BPH; n = 30), with prostate cancer without metastasis (T1,2,3pN0M0; n = 30) and with locally advanced prostate cancer and/or metastatic disease (T3,4pN1,2M1; n = 19). sCD44std and sCD44v6 concentrations were not significantly different among the four groups studied, with few patients' levels outside the central 95% reference intervals. The mean sCD44v5 concentrations of both prostate cancer and BPH patients were significantly lower than those of the controls. There was no significant difference between the soluble CD44 concentrations of the two groups of prostate cancer patients studied. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum is not suitable for providing additional prognostic information on patients with prostate cancer.

Adult↗

Negative prostatic biopsies in patients with a high risk of prostate cancer. Is the combination of endorectal MRI and magnetic resonance spectroscopy imaging (MRSI) a useful tool? A preliminary study.

OBJECTIVE: Repeated biopsies in patients with a high risk of prostate cancer only allow a small proportion of new cancer diagnosis. The aim of this study was to evaluate the use of combined MRI and magnetic resonance spectroscopy imaging (MRSI) for these patients. METHODS: Between April 2003 and April 2004, 42 patients with negative multiple cores prostatic biopsies and serum PSA>4 ng/ml underwent a combined MRI/MRSI analysis. Suspicious zones on standard MRI included low intensity signals on T2 weighted images. A high choline+creatine-to-citrate ratio defined a MRSI suspicious zone. A 10 cores following peripheral biopsy scheme was done to which were added supplementary biopsies on the MRI/MRSI suspicious zones. RESULTS: The mean age was 62.3 years (51-74), the mean pre-biopsy serum PSA was 12 (3.87-35), the mean free/total PSA ratio was 11% (5-20). The mean number of previous prostate biopsy rounds was 2.04. 15 prostate cancers were diagnosed (35.7%). In 9 cases, abnormal MRI/MRSI findings and positive biopsy sites were located on the same prostatic zones. In 5 cases, MRSI alone located the positive biopsy zones. Sensitivity of combined MRI/MRSI in this study was 73.3%; specificity, positive predictive value, negative predictive value and accuracy were 96.3%, 91.6%, 86.6% and 88% respectively. CONCLUSIONS: This preliminary study shows that the combination of MRI and MRSI might be able to guide and therefore limit the number of iterative biopsies and cores for patients who are at high risk of having a prostate cancer. In some cases, MRSI alone allows identification of neoplasic prostatic zones. Other studies are needed to confirm these data.

Aged↗

Volume-based evaluation of serum assays for new prostate-specific antigen isoforms in the detection of prostate cancer.

OBJECTIVES: Recently, disease-specific isoforms of the prostate-specific antigen (PSA) have been identified. We evaluated the efficacy of precursor isoforms of PSA (pPSA) and an internally cleaved form of PSA referred to as the benign prostatic hyperplasia-associated PSA (BPSA) for the detection of prostate cancer. METHODS: Serum concentrations of [-2], [-4], and [-7]pPSA, sum pPSA ([-2] + [-4] + [-7]pPSA), and BPSA were retrospectively measured in 43 selected men. The median total PSA levels in men with and without cancer were 6.5 microg/L (range 0.4 to 12.1 microg/L) and 6.1 microg/L (range 3.7 to 21.5 microg/L), respectively. Of the 43 men, 15 had clinical T2 prostate cancer with an ultrasound-estimated prostate volume (PV) of greater than 50 mL, 13 had clinical T2 prostate cancer with PV less than 25 mL, and 15 were prostate cancer free with PV greater than 50 mL. RESULTS: The median values for BPSA, free-to-total PSA ratio (f/tPSA), and benign-to-total PSA ratio (B/tPSA) differed statistically between men with cancer and a PV less than 25 mL and men with cancer and a PV greater than 50 mL (P <0.05) and between the men with cancer and a PV less than 25 mL and men without cancer and a PV greater than 50 mL (P <0.005). All evaluated variables had no correlation with tumor volume in 15 men who had undergone radical prostatectomy. CONCLUSIONS: In this preliminary study, the level of [-2], [-4], sum pPSA, and BPSA seemed to be PV related, but only BPSA and B/tPSA and f/tPSA were significantly associated with PV. Therefore, pPSA did not aid in better discriminating cancer from noncancer.

Adenocarcinoma↗

Microvessel density as a molecular marker for identifying high-grade prostatic intraepithelial neoplasia precursors to prostate cancer.

BACKGROUND: Existing clinical data have shown that high-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor to prostate cancer (CaP). Criteria to distinguish HGPIN that progress to CaP from those that do not remain poorly defined. Our objective was to evaluate microvessel density as a molecular marker for distinguishing HGPINs that have the potential of progressing to cancer. MATERIALS AND METHODS: Human prostatic tissue samples were collected randomly from 50 prostatectomy and cystoprostatectomy patients. Formalin-fixed and paraffin-embedded sections were used for immunohistochemical localization of rabbit anti-human von Willebrand factor VIII (vWF) IgG, mouse anti-high molecular weight cytokeratin 34BE-12 in basal cells, and mouse anti-heparan sulphate proteoglycan (HSPG) IgGs in basement membranes associated with benign prostatic hyperplasia (BPH), PIN associated with some BPH (isolated PIN), and PIN associated with CaP. RESULTS: Analysis of immunostaining data showed that PINs could be categorized according to their distributions within and outside 2 standard deviations (SD) of the mean for microvessel density. The average number of microvessels was significantly higher (P < 0.0001) in PINs associated with Gleason score 7 tumors than those associated with Gleason scores 4-6 (P < 0.1328) or 8 and 9 tumors (P < 0.1708). Morphologically, PINs within 2 SD were composed of low- and high-grade type, whereas those outside 2 SD of microvessel density were predominantly of high-grade type. Cytokeratin and HSPG localization patterns also showed differences in PINs found within and outside 2 SD of microvessel density. We found localization of cytokeratin 34BE-12 in basal cells of specimens with BPH alone, isolated PIN, and PIN associated with CaP within 2 SD, whereas many PINs outside 2 SD showed disruptions in cytokeratin localization. The basement membranes of PINs within 2 SD of microvessel density were relatively intact, whereas those outside 2 SD were fragmented. CONCLUSIONS: Our immunostaining data indicates that once HGPIN is found in the initial prostatic biopsy, it should be evaluated for microvessel density by localization of vWF. Our data indicate that characteristics of HGPIN can be augmented by evaluations of cytokeratin and HSPG molecular markers to assess the potential of HGPIN progression to malignancy. When biopsy samples show HGPIN with increased microvessel density and disrupted cytokeratin and HSPG markers, the patient may be a candidate for repeat biopsy. Since our study is limited to 50 prostate tissue samples, we emphasize that our conclusion is tentative and ought to be confirmed in a study with a larger sample size. This is the first report to show that microvessel density may distinguish HGPIN that is a precursor to prostate cancer.

Aged↗

p63 is a prostate basal cell marker and is required for prostate development.

The p53 homologue p63 encodes for different isotypes able to either transactivate p53 reporter genes (TAp63) or act as p53-dominant-negatives (DeltaNp63). p63 is expressed in the basal cells of many epithelial organs and its germline inactivation in the mouse results in agenesis of organs such as skin appendages and the breast. Here, we show that prostate basal cells, but not secretory or neuroendocrine cells, express p63. In addition, prostate basal cells in culture predominantly express the DeltaNp63alpha isotype. In contrast, p63 protein is not detected in human prostate adenocarcinomas. Finally, and most importantly, p63(-/-) mice do not develop the prostate. These results indicate that p63 is required for prostate development and support the hypothesis that basal cells represent and/or include prostate stem cells. Furthermore, our results show that p63 immunohistochemistry may be a valuable tool in the differential diagnosis of benign versus malignant prostatic lesions.

Adenocarcinoma↗

Decreased concentrations of prostate-specific antigen and human glandular kallikrein 2 in malignant versus nonmalignant prostatic tissue.

OBJECTIVES: To study quantitatively the relative expression of human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) in paired (from the same patient) cancerous and noncancerous prostatic tissue to evaluate whether these proteins are overexpressed or underexpressed in cancer. METHODS: We studied 14 patients who underwent radical retropubic prostatectomy for prostate cancer. Cancerous and adjacent normal tissues were excised and then extracted to prepare cytosolic extracts. The extracts were analyzed for total protein, and for hK2 and PSA using sensitive and specific immunofluorometric procedures. RESULTS: PSA was present in the prostatic extracts at about 50 to 100 times higher amounts than hK2. The correlation between PSA and hK2 values was good. Both prostate kallikreins were expressed more in noncancerous than in cancerous prostatic tissue. CONCLUSIONS: Our results demonstrated that both PSA and hK2 are down-regulated in prostate cancer compared with noncancerous tissue. The degree of down-regulation was higher for PSA than for hK2. The mechanism and physiologic consequences of this down-regulation are unknown.

Aged↗

High-grade prostatic intraepithelial neoplasia with adjacent atypia is associated with a higher incidence of cancer on subsequent needle biopsy than high-grade prostatic intraepithelial neoplasia alone.

OBJECTIVES: High-grade prostatic intraepithelial neoplasia (HGPIN) is often considered a premalignant lesion of the prostate. Its incidence ranges from 0.7% to 20% in all prostate biopsies, and patients with HGPIN on initial biopsy are reportedly found to have a higher risk of cancer on subsequent biopsy. The purpose of our study was to determine the incidence of HGPIN in our patients who underwent prostate biopsy and to determine whether a further pathologic subclassification of HGPIN between HGPIN alone and HGPIN with adjacent atypical glands has any prognostic value in predicting the rate of prostate cancer on subsequent prostate biopsy. METHODS: A total of 485 patients who underwent prostate biopsy between January 1998 and October 1999 were included in the study. Each set of slides was reviewed by a single urologic pathologist to determine the presence of HGPIN alone or HGPIN with adjacent atypical glands. If any HGPIN was identified, a repeat biopsy was performed, and the presence of cancer was recorded. RESULTS: The overall incidence of HGPIN alone and HGPIN with adjacent atypical glands on initial biopsy was 33 (6.8%) of 485. Of these 33 patients, 21 (64%) had HGPIN alone and 12 (36%) had HGPIN with adjacent atypical glands. Three (14%) of 21 patients with HGPIN alone were found to have cancer on subsequent biopsy compared to 9 (75%) of 12 patients with HGPIN with adjacent atypia on initial biopsy. This difference is statistically significant (P <0.005). CONCLUSIONS: The incidence of HGPIN alone in our experience is 4.3% (21 of 485). Patients with HGPIN with adjacent atypical glands suspicious for cancer have a significantly higher incidence of cancer on subsequent biopsy than patients with HGPIN alone.

Aged↗

Biochemical outcome for hormone-naive patients with Gleason score 3+4 versus 4+3 prostate cancer undergoing permanent prostate brachytherapy.

OBJECTIVES: To determine the effect of the dominant pattern in Gleason score 7 histologic findings on biochemical no evidence of disease survival for hormone-naive patients undergoing permanent prostate brachytherapy. METHODS: A total of 114 hormone-naive patients with Gleason score 7 histologic findings underwent transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1c-T3a NxM0 adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. Sixty-four patients were diagnosed with Gleason score 3+4 and 50 with Gleason score 4+3 prostate cancer. Twenty-one patients were implanted with either palladium 103 or iodine 125 monotherapy, and 93 patients received supplemental external beam radiotherapy with a brachytherapy boost. The median patient age was 69 years (range 49 to 79). The median follow-up was 46.4 months (range 20 to 80). The American Society for Therapeutic Radiology and Oncology consensus definition was used to determine the biochemical disease-free survival. RESULTS: The actuarial 5-year biochemical disease-free survival rate was 90.3%. No statistically significant difference in outcome was found when stratified by the dominant pattern in Gleason score 7 histologic features (89.4% versus 91.5% for 3+4 and 4+3, respectively, P = 0.700). The biochemical no evidence of disease survival analysis in terms of the Gleason cohorts revealed no difference in terms of the choice of isotope, use of supplemental external beam radiotherapy, or preimplant prostate-specific antigen level. The median and mean postimplant prostate-specific antigen level was less than 0.1 ng/mL and 0.12 +/- 0.20 ng/mL, respectively, without a significant difference between Gleason score 3+4 and 4+3. CONCLUSIONS: Our results indicate that the 5-year biochemical outcome with a hormone-naive prostate brachytherapy approach that uses multiple periprostatic seeds is not dependent on Gleason score 3+4 versus 4+3 histologic features.

Adenocarcinoma↗

Can volume measurement of the prostate enhance the performance of complexed prostate-specific antigen?

We assessed whether volume-based complexed prostate-specific antigen (cPSA) indices could enhance prostate cancer detection in men with serum total PSA (tPSA) between 2.5 and 10.0 ng/mL. Between December 1998 and April 2000, cPSA assay was measured in 480 men who underwent transrectal ultrasound-guided prostate biopsies at 7 institutions. We compared the usefulness of cPSA and its indices with the ratio of free PSA (fPSA) to tPSA (percent fPSA) for early detection of prostate cancer. Overall, 168 men (35%) had cancer. In the 341 men with tPSA between 4.01 and 10.0 ng/mL at approximately 90% sensitivity and areas under the receiver operating characteristics curve, the performances of volume-based parameters were significantly better (P <0.05) than those of tPSA and cPSA. In the 139 men with tPSA between 2.5 and 4.0 ng/mL, at 90% sensitivity, the specificity of the ratio of cPSA to tPSA (percent cPSA) was best, followed by cPSA density (cPSAD). In the 101 men with the history of a previous prostate biopsy, at approximately 90% sensitivity, the specificity of cPSAD was significantly better than those of tPSA and percent fPSA (P <0.05). In the 371 men with a total prostate volume of >or=30 cm(3) at approximately 90% sensitivity, the specificity of the cPSAD was significantly better than that of tPSA, percent fPSA, and cPSA (P <0.05). In the 109 men with a total prostate volume of <30 cm(3), at 90% sensitivity the specificity of cPSA and cPSAD was better than that of percent fPSA. In conclusion, volume-based cPSA can modestly enhance the performance of cPSA.

Humans↗

Significance of prostatic intraepithelial neoplasia on prostate needle biopsy.

Prostatic intraepithelial neoplasia (PIN) is a putative premalignant change in the human prostate. Previously, the spatial association of PIN with invasive carcinoma has been described in the study of total prostatectomies. PIN is frequently recognized in prostate needle biopsy specimens in which no carcinoma is apparent. To further define the potential significance of PIN, we performed repeat ultrasound-guided prostate needle biopsy in 21 men who had PIN identified on prostate biopsy performed because of an abnormal finding on digital rectal examination. Twelve patients (57%) had carcinoma identified on their second procedure including all who had intermediate- and high-grade PIN on the initial procedure. Prostate-specific antigen correlated with PIN grade and carcinoma on the secondary procedure, although this did not achieve statistical significance. Men with PIN on prostate needle biopsy should undergo repeat sampling to exclude missed carcinoma.

Adenocarcinoma↗