Epidural anaesthesia for caesarean section in an achondroplastic dwarf

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. Telomerase activation has been seen in many immortal cell lines and cancers. Telomerase activity was analyzed in prostate carcinoma; in coexistent prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), atrophy and normal tissue; and in benign prostate glands. Telomerase activity was detected in 80 of 87 (92%) prostate cancers. Forty-one matched samples (from a total of 32 cases) were available for comparative analysis. The presence of telomerase activity in adjacent PIN, BPH, and normal tissue was correlated with telomerase activity in the malignant epithelium. In these adjacent tissues, telomerase activity was found in 11 of 15 (73%) PINs, 13 of 26 (50%) BPHs, and 1 of 6 (16%) atrophy and 4 of 11 (36%) normal tissues. In contrast to the BPH tissue from cancer-bearing glands, all 16 BPH specimens from patients only diagnosed with BPH were telomerase activity negative. In cancer samples, there was no correlation between telomerase activity and Gleason grade or preoperation prostate-specific antigen level. Our data indicate that telomerase activity is present in most prostate cancers. The high rate of telomerase activity in the benign-appearing areas of these glands may be attributed either to the presence of occult cancer cells or to early molecular alterations of cancer that were histologically inapparent.     

The quotient of prostate-specific antigen and prostate volume. Improved differentiation between benign prostatic hyperplasia and locally circumscribed prostate cancer

Absolute serum prostate-specific antigen (PSA) values are of little help in the identification of locally confined prostatic cancer (PCA), because of a considerable overlap with the PSA values found in benign prostatic hyperplasia (BPH). Prostate gland volumes were estimated sonographically in 112 patients using the product of the three maximal diameters (longitudinal, anterior-posterior, transverse) and the factor 0.52. PSA was determined with a monoclonal immunoenzymetric assay (Tandem-E, Hybritech). The prostates were removed by either transvesical prostatectomy (for BPH) or radical retropubic prostatovesiculectomy (for PCA). In each case the diagnosis was verified by systematic histological examination. The ratio of serum PSA to estimated prostate volume did not exceed 0.4 ng/(ml x ml) in any of the 74 patients with BPH, whereas 23 of the 38 patients with PCA had a ratio above 0.4 ng/(ml x ml). The information provided by the PSA-prostate volume ratio is superior to absolute PSA values in preoperative differentiation between BPH and PCA. With a PSA-prostate volume ratio over 0.4 ng/(ml x ml) patients are at high risk for PCA and should be evaluated by prostate biopsy.     

Preliminary immunohistochemical characterization of a monoclonal antibody (PRO:4-216) prepared from human prostate cancer nuclear matrix proteins

OBJECTIVES: A nuclear matrix protein (PC-1) was previously identified and reported to be present only in human prostate cancer but absent in tissue from the same prostate containing either benign prostatic hyperplasia (BPH) or normal prostate tissue. The PC-1 protein was identified by high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and exhibited a molecular mass of 56 kDa and an isoelectric point of 6.58. This work investigates the immunohistochemical characterization of PRO:4-216, a monoclonal antibody to PC-1. METHODS: Areas of the 2D-PAGE gels containing the human prostate cancer nuclear matrix proteins near PC-1 were isolated, eluted, and injected into mice to develop monoclonal antibodies. Antibodies were screened by immunofluorescence for nuclear reactivity to a human prostate cancer cell line (LnCaP) and by 1D and 2D Western blots for reactivity with prostate cancer nuclear matrix proteins. Monoclonal antibodies from the selected clones were affinity purified. The monoclonal antibody PRO:4-216 was used to analyze frozen tissue from 20 cancerous, 22 BPH, and 22 normal regions from fresh human prostate specimens. Tissue sections were analyzed for their immunohistochemical (IHC) (horseradish peroxidase) staining. RESULTS: Using a reference value for positive staining at an IHC score of greater than 50, 85% (17 of 20) of the cancerous, 5% (1 of 22) of the BPH, and 9% (2 of 22) of the normal prostate tissues stained positive. The one BPH and two normal tissues that stained positive were taken from prostates in which the adjacent cancerous tissue also demonstrated high IHC scores (greater than 225). CONCLUSIONS: These data demonstrate nuclear reactivity on fresh frozen human prostate cancer tissue for the monoclonal antibody PRO:4-216. PRO:4-216 may aid in distinguishing normal prostate and BPH from cancerous tissue.     

Secretion of insulin-like growth factors and their binding proteins by human normal and hyperplastic prostatic cells in primary culture

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Because insulin-like growth factors (IGFs) with their binding proteins (IGFBPs) are involved in the control of cellular proliferation, differentiation, and metabolism, we compared their secretion by prostatic epithelial and stromal cells in primary culture from the four different zones of normal prostate and from hyperplastic tissue to assess their contributions to the hyperplastic development. IGF-I could not be detected in the conditioned medium from either epithelial or stromal cells from normal and BPH tissues. IGF-II concentrations were the same in the conditioned medium from the epithelial cells of the different zones of the normal prostate and that of BPH cells. IGF-II concentrations secreted in stromal cell culture medium, however, were higher in the periurethral zone than in the peripheral and central zones. Moreover, in the periurethral zone, stromal cells secreted higher concentrations of IGF-II than did epithelial cells. Also, BPH stromal cells secreted more IGF-II than did BPH epithelial cells. IGFBP-3, IGFBP-2, and IGFBP-4 were all secreted by both epithelial and stromal cells. In contrast, IGFBP-5 was only produced by stromal cells of the periurethral zone of the normal prostate and BPH tissue. IGFBP-3 was predominantly secreted by normal stromal cells of the transitional zone. We observed that BPH stromal cells presented the same pattern of IGF-II and IGFBP production as normal stromal cells of the periurethral zone. These data support the hypothesis that the periurethral zone is the main region of the prostate implicated in the development of BPH. They also suggest that the variability in both IGF-II secretion and the secreted forms of IGFBPs, depending on anatomical location within the organ, may be important for the autocrine regulation of normal and hyperplastic prostate growth.     

Prostate specific antigen in the expressed prostatic fluid of men with benign prostatic hyperplasia and prostate carcinoma

PURPOSE: We tested the hypothesis that the histochemically demonstrated prostate specific antigen (PSA) content of prostate carcinoma cells does not necessarily reflect PSA production and secretion by evaluating expressed prostatic fluid. MATERIALS AND METHODS: Expressed prostatic fluid and serum from 152 men with clinical benign prostatic hypertrophy (BPH), 132 with histologically proved BPH and 46 with prostate carcinoma were analyzed with the Hybritech PSA assay. RESULTS: Expressed prostatic fluid PSA levels from carcinoma patients (median 1.70 mg./ml., mean 2.25) were significantly higher than in the histologically proved BPH group (median 1.28 mg./ml., mean 1.42, p < 0.05). CONCLUSIONS: PSA concentration is increased in the expressed prostatic fluid of prostates of men with carcinoma compared to those with histological BPH. This finding may be a functional manifestation of a field change or paracrine effects within the prostate.     

The precursor form of the human kallikrein 2, a kallikrein homologous to prostate-specific antigen, is present in human sera and is increased in prostate cancer and benign prostatic hyperplasia

Prostate-specific antigen (PSA, hK3) is a diagnostic marker for prostatic cancer but lacks the specificity to sufficiently distinguish between prostatic cancer and benign prostatic hyperplasia (BPH). Human glandular kallikrein 2 (hK2) has been proposed as a potential diagnostic marker for prostate cancer that could complement the current PSA test. Recently we demonstrated that proPSA is present in prostate cancer sera. This study examines the expression of prohK2 in prostate cells and its presence in human sera. Western blot analysis was used to assess prohK2 expression in the human carcinoma cell line, LNCaP. A highly specific and sensitive dual monoclonal immunoassay for prohK2 was developed and used to assess the presence of prohK2 in human sera. prohK2 was detected in the spent media of LNCaP cells. Furthermore, prohK2 was present at immunodetectable concentrations in human sera, and its concentration was increased in prostatic cancer and BPH. These results indicate for the first time that prohK2 is secreted by human prostate cells and is a major component of uncomplexed (free) hK2 in human sera. In addition, prohK2 in human sera is associated with prostate disease and thus may be a useful marker for prostatic cancer and BPH.     

Ratio of free-to-total prostate specific antigen in serum cannot distinguish patients with prostate cancer from those with chronic inflammation of the prostate

PURPOSE: We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy. RESULTS: The median values of total, free and percentage of free PSA were 4.11 microg./l., 0.75 microg./l. and 20.4% in patients with BPH, 10.0 microg./l., 0.84 microg./l. and 8.5% in those with prostate cancer, and 7.60 microg./l., 1.23 microg./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis. CONCLUSIONS: Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.     

Epidemiological study on diet, smoking and alcohol drinking in the relationship to prostatic weight

BACKGROUND: There have been no epidemiological studies on the relationship between the prostatic weight and blood examination data. This study was carried out to evaluate this relationship. SUBJECTS AND METHODS: Blood examination (beta-carotene, GOT, GPT, total cholesterol, etc.) and measurement of the prostatic weight were performed in 432 subjects aged 50 years or more of a town in Japan, and the possible relationship between blood analysis data and the prostatic weight was evaluated. The prostates were examined by transrectal ultrasonography (TRUS) and classified into the normal prostate and benign prostatic hypertrophy (BPH). The prostatic weight was measured by Watanabe's method based on TRUS images. In addition, the possible association between the prostatic weight and smoking, drinking, height, body weight, or age was evaluated. RESULTS: Analysis by the logistic procedure and the general linear models procedure showed a significant positive correlation between the normal prostatic weight and beta-carotene, height, as well as body weight and a significant negative correlation between the normal prostatic weight and smoking. Comparison between subjects with the normal prostate and those with BPH suggested that serum beta-carotene is a significant positive risk for BPH, and HDL-cholesterol, drinking, and smoking are negative risks by logistic procedure analysis. CONCLUSION: It was thought that serum beta-carotene and smoking are associated with the development of BPH.     

Studies on the expression of fibroblast growth factors and fibroblast growth factor receptors in human prostate cancer

PURPOSE: We tried to clarify the role of fibroblast growth factors (FGFs) and those receptors (FGF-Rs) in cell proliferation of human prostate cancer. METHODS: The mRNA expression of FGF1, FGF2, FGF7, FGF-R1, FGF-R2 (IIIb), and FGF-R2 (IIIc) was investigated by RT-PCR in androgen sensitive cells (LNCaP), androgen-independent cells (PC3) and primary cultured stromal (PS) and epithelial cells (PE) from benign prostatic hyperplasia (BPH). Expression of the mRNA of FGF-R1, FGF-R2 (IIIb) and FGF-R2 (IIIc) in human prostate cancer tissue was similarly analyzed. Furthermore, the level of FGF-R1 expression in human prostate cancer was measured by semi-quantitative RT-PCR. RESULTS: FGF-R1 mRNA was detected in LNCaP, PC3 and the primary cultured stromal cells of BPH. FGF-R2 (IIIb) was seen in LNCaP cells and the primary cultured epithelial cells of BPH, while FGF-R2 (IIIc) was only observed in PC3. FGF1 mRNA was expressed in LNCaP and PC3, while FGF2 mRNA was in PC3 alone. The expression of FGF7 mRNA was detected only in the primary cultured stromal cells. Of 17 patients with human prostate cancer, FGF-R2 (IIIb) was detected in 2 and FGF-R2 (IIIc) in 15. Histological type of two cases having FGF-R2 (IIIb) were well differentiated adenocarcinoma. The mRNA levels of FGF-R1 in poorly and moderately differentiated types were significantly higher than those in well differentiated ones (p < 0.05). CONCLUSION: These findings suggest that several changes of expression in FGFs and FGF-Rs may correlate with malignant progression of human prostate cancer.     

The clinical utility of measuring free-to-total prostate-specific antigen (PSA) ratio and PSA density in differentiating between benign prostatic hyperplasia and prostate cancer

OBJECTIVE: To evaluate the role of free-to-total prostate-specific antigen ratio (f/tPSA), prostate volume and PSA density in differentiating between men with prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study comprised 51 patients who were assessed after transurethral electroresection of the prostate (16 with prostate cancer and 35 with BPH). Patients with a tPSA of < or = 4.0 ng/mL and > or = 30.0 ng/mL were excluded from the analysis. Total and fPSA were measured using an immunoradiometric assay and prostate volume was determined by transrectal ultrasonography. The incidence of prostate cancer and BPH was then compared with the PSA variables to determine specificity and predictive value. RESULTS: Most patients with BPH had a tPSA of 4.0-6.0 ng/mL; no patients with BPH had a tPSA of > 20.0 ng/mL. Most patients with prostate cancer had a f/tPSA of 6-10%. The area under the receiver operating characteristic curve for f/tPSA was significantly greater than that for tPSA (P < 0.003). CONCLUSIONS: The measurement of f/tPSA and PSA density increase the specificity of the differential diagnosis between BPH and prostate cancer.     

Carcinogenic responses of transgenic heterozygous p53 knockout mice to inhaled 239PuO2 or metallic beryllium

BACKGROUND: To investigate if serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of deoxypyridinoline (D-Pyr) are useful markers of bone metastasis in patients with prostate carcinoma, we measured these markers in patients with untreated benign prostatic hyperplasia (BPH) and untreated prostate carcinoma (PCA). METHODS: Serum PICP, ICTP and urinary D-Pyr levels were determined in 53 patients; 16 patients with BPH, 15 patients with PCA without bone metastasis (stage A, B, C and D1) and 22 patients with PCA with bone metastasis (stage D2). At the same time correlations among these markers and serum total alkaline phosphatase (ALP) activity were studied. RESULTS: Serum PICP, ICTP and urinary D-Pyr levels in the PCA patients with bone metastasis were significantly higher than those of BPH. The serum levels of PICP in patients with PCA with bone metastasis group were significantly higher than those of without bone metastasis group. The serum levels of ICTP in patients with PCA without bone metastasis group were significantly higher than those of BPH group, while no significant difference was observed between PCA group with and without bone metastasis. In the PCA patients with bone metastasis, serum PICP and serum total alkaline phosphatase (ALP) activity were significantly correlated (r = 0.80). In these patients, serum ICTP and urinary D-Pyr levels were also significantly correlated (r = 0.70). CONCLUSION: These results suggest that serum PIPC, ICTP and urinary D-Pyr are the useful markers to quantitate bone metastasis in the patients with PCA. Moreover, the determination of serum ICTP levels may be significant for detecting occult bone metastasis in the patients with PCA.     

Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.     

Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma

BACKGROUND: The p27KIP1 gene, whose protein product is a negative regulator of the cell cycle, is a potential tumor suppressor gene; however, no tumor-specific mutations of this gene have been found in humans. This study was undertaken to identify and to assess potential alterations of p27KIP1 gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. METHODS: We analyzed 130 prostate carcinomas from primary and metastatic sites, as well as prostate samples from normal subjects and from patients with BPH. Immunohistochemistry and in situ hybridization were used to determine the levels of expression and the microanatomical localization of p27 protein and messenger RNA (mRNA), respectively. Immunoblotting and immunodepletion assays were performed on a subset of the prostate tumors. Associations between alterations in p27KIP1 expression and clinicopathologic variables were evaluated with a nonparametric test. The Kaplan-Meier method and the logrank test were used to compare disease-relapse-free survival. Prostate tissues of p27Kip1 null (i.e., knock-out) and wild-type mice were also evaluated. RESULTS: Normal human prostate tissue exhibited abundant amounts of p27 protein and high levels of p27KIP1 mRNA in both epithelial cells and stromal cells. However, p27 protein and p27KIP1 mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions. Furthermore, p27Kip1 null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27KIP1 mRNA but either high or low to undetectable levels of p27 protein. Primary prostate carcinomas expressing lower levels of p27 protein appeared to be biologically more aggressive (two-sided P = .019 [Cox regression analysis]). CONCLUSIONS/IMPLICATIONS: On the basis of these results, we infer that loss of p27Kip1 expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer.     

Extended survivability of prostate cancer cells in the absence of trophic factors: increased proliferation, evasion of apoptosis, and the role of apoptosis proteins

This project was undertaken to study the survival properties of various prostate cells, including normal (NHP), BPH (benign prostate hyperplasia), primary carcinoma (PCA), and metastatic prostate cancer cells (LNCaP, PC3, and Du145), in the absence of trophic factors. Cell proliferation and cell death were quantitated by enumerating the number of live cells using MTS/PMS kit and of dead (apoptotic) cells using 4',6-diamidino-2-phenylindole dihydrochloride nuclear staining. These cells demonstrated an overall survivability in the order of BPH < NHP < LNCaP < PC3 < PCA < Du145. Upon growth factor deprivation, NHP/BPH cells rapidly underwent apoptosis, leading to a decreased number of live cells. PCA/PC3/Du145 cells, in contrast, demonstrated an initial phase of aggressive growth during which apoptosis rarely occurred, followed by a "plateau" phase in which cell loss by apoptosis was compensated by cell proliferation, followed by a later phase in which apoptosis exceeded the cell proliferation. LNCaP cells demonstrated survival characteristics between those of NHP/BPH and PCA/PC3/Du145 cells. We concluded that the increased survivability in prostate cancer cells results from enhanced cell proliferation as well as decreased apoptosis. The molecular mechanisms for evasion of apoptosis in prostate cancer cells were subsequently investigated. Quantitative Western blotting was used to examine the protein expression of P53 and P21WAF-1, Bcl-2 and Bcl-X(L) (anti-apoptotic proteins), and Bax, Bak, and Bad (proapoptotic proteins). The results revealed that, upon trophic factor withdrawal, NHP and BPH cells upregulated wild-type p53 and proapoptotic proteins Bax/Bad/Bak and down-regulated the expression of P21. Furthermore, NHP and BPH cells endogenously expressed little or no Bcl-2. In sharp contrast, prostate cancer cells expressed nonfunctional P53 and various amounts of Bcl-2 proteins. Upon deprivation, these cancer cells up-regulated P21 and Bcl-2 and/or BclX(L), lost response to withdrawal-induced up-regulation of Bax/Bad/Bak or decreased or even completely lost Bax expression and expressed some novel proteins such as P25 and P54/55 complex. These data together suggest that prostate cancer cells may use multiple molecular mechanisms to evade apoptosis, which, together with increased proliferation, contribute to extended survivability of prostate cancer cells in the absence trophic factors.     

Significance of abnormal diploid DNA histograms in localized prostate cancer and adjacent benign prostatic tissue

To clarify the relationship of DNA ploidy to tumor grade and volume, 32 clinical Stage B prostate cancers, with low and high Gleason scores and small and large tumor volumes, were compared with adjacent histologically normal prostate tissue and with samples from benign prostatic hyperplasia (BPH). All 22 samples from benign glands were diploid, with 2.7 +/- 1.2% tetraploid (4C) cells. Samples from cancer-bearing glands were considered diploid (normoploid) if they had a major diploid (2C) peak and a small 4C peak with the percentage of cells falling within 3 standard deviations of the figure found for BPH. Abnormal ploidy included abnormal diploid (6.3-14.9% 4C), tetraploid (> or = 15% 4C), and aneuploid samples (peaks not at 2C or 4C). Abnormal DNA ploidy was found to be related to tumor volume. All five tumors smaller than 0.4 cm3 and their adjacent benign tissue were normoploid; however, 10 of 13 cancers with volumes of 0.4-1 cm3 had abnormal ploidy (9 abnormal diploid, 1 tetraploid) and 6 of 9 of the adjacent benign tissue samples also were abnormal diploid. All larger tumors (> 1 cm3) showed abnormal ploidy (7 abnormal diploid, 3 tetraploid, 5 aneuploid). For large tumors, abnormal ploidy was present in 10 of 13 of the adjacent benign areas (8 abnormal diploid, 2 benign areas that were clearly aneuploid). Abnormal diploid cancers are intermediate forms between diploid and tetraploid tumors, as defined above. Although they have fewer 4C cells than tetraploid cancers, they have equivalent numbers of hypertetraploid cells (BPH: 1.3 +/- 0.9%; abnormal diploid: 10.8 +/- 5.4%; tetraploid: 11.1 +/- 6.8% hypertetraploid cells). Thus, the authors propose that abnormal diploid cancers represent an early stage in ploidy progression. DNA ploidy abnormalities also occur in benign prostatic tissue adjacent to many prostate cancers, consistent with the concept that human prostatic cancer is a field-change disease.     

Morphology of brain stem lesion and bera findings after 60Co irradiation

BACKGROUND: We assessed the frequency and molecular basis of p53 mutations in clinically localized prostatic adenocarcinoma. METHODS: Prostate specimens were examined from 100 patients with clinically localized prostatic adenocarcinoma and 13 patients with benign prostatic hyperplasia (BPH). Mutations producing nuclear accumulation of p53 were detected immunohistochemically. Exon-specific mutations were analyzed by polymerase chain reaction amplification and single strand conformation polymorphism (PCR-SSCP) and sequenced. RESULTS: p53 accumulation was detected in 5 tumors using antibody DO-1, and in 4 of these using antibody PAb 1801, but not in BPH. PCR-SSCP detected mutations in all 5 tumors, with alterations in exon 5 for 1 tumor, exon 6 for 3 tumors, and exon 7 for 1 tumor. An exon 6 mutation was also found in a tumor with no anti-p53 staining. CONCLUSIONS: p53 mutations are uncommon in clinically localized prostatic adenocarcinoma and absent from BPH. 5 of the 6 mutations were derived from locally invasive, prostate carcinomas, supporting the hypothesis that mutation of p53 is a late event in prostate carcinoma progression.     

The role of prostate specific antigen in diagnosis of localized adenocarcinoma of the prostate. Nara Uro-Oncology Research Group

The number of cases of prostate carcinoma (PCA) is steadily inceasing in Japan. The clinical application of a reliable tumor marker, prostate specific antigen (PSA) for the diagnosis, as well as the increasing elderly population in Japan may account for this increase. The subjects were patients at the Nara Medical University and its affiliated hospitals; 1) 687 cases without PCA were evaluated for age-specific PSA and the incidence of abnormal PSA following urological manipulations, 2) 135 cases with histological proven BPH by transurethral resection of prostate (TUR-P) were examined for PSA density (PSAD) and positive PSA rate in BPH, 3) 135 cases receiving a needle biopsy with suspicion of PCA were examined for the efficacy of PSA and PSAD and other parameters, and 4) 459 PCA cases treated between 1988 and 1994, were examined for specific PSA and PSAD values by stage and degree of cell differentiation. The PSA assay used in this study was MARKIT-M PA (normal range < or = 3.6 ng/ml). The PSA was decreased gradually with age in non-PCA patients, and abnormal PSA was found in 5.5% of these patients following manipulations. The average PSA was 2.95 +/- 2.03 ng/ml in 130 BPH patients (mean age: 71.1 +/- 7.0 years old. and average prostate volume: 32.9 +/- 16.1 ml). And abnormal PSA level (more than 3.61 ng/ml) was found in 22.3%. The mean PSAD was 0.1.0 +/- 0.06, and PSAD was below 0.15 in 86.1% of these BPH cases. Among the 135 cases receiving a needle biopsy, 33 cases had PSA values between 3.61 and 10.0 ng/ml. Of these cases, PCA was found in 18.5% of the 27 cases with a PSAD below 1.5, and in 33.3% of the 6 cases with a PSAD over 1.5. PSA and PSAD were proportionally increased with stage, and a significant difference in the PSA value was observed between stage B1 and B2, and stage C and D (P < 0.05). However, PSA and PSAD values were not significantly correlated with the cell differentiation in PCA stage A2-C. In total, PSA was 18.1 ng/ml in well, 23.9 ng/ml in moderately and 35.9 ng/ml in poorly differentiated type PCA. The positive rate of PSA was 22.3, 65.4 and 83.5%, that of prostate acid phosphatase (PAP) was 10.0, 17.8 and 45.8%, and that of GSM was 25.0, 14.7 and 68.4%, in BPH, stage A PCA and stage BPCA, respectively. In conclusion, PSA is the most reliable tool in the diagnosis of localized PCA. However, the differential diagnosis of BPH and localized PCA is difficult when the PSA value is between 3.61 and 10.0 ng/ml, and accurate staging of localized PCA is difficult with PSA or PSAD alone. At present, it is necessary to use all possible tools for the early detection of localized PCA, and to perform the needle biopsy in all PCA-suspicious cases.