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A lectin histochemistry comparative study in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma.

The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH differed from that of normal prostate in having more intense staining with DSA, HPA, UEA-I and AAA, and in showing lesser staining with WGA and SBA. Prostatic carcinoma differed from normal prostates in displaying the more intense labeling with PNA, DSA, SBA, DBA, UEA-I and AAA, and in having lesser labeling with WGA. The main differences in labeling pattern between prostatic carcinoma and BPH were that the latter specimens showed more marked staining with PNA, DSA, DBA, SBA, UEA-I and AAA, and lesser staining with WGA and HPA. The staining patterns of SNA, MAA, ConA, LCA and GNA were similar in all three groups of specimens. For most of the lectins studied, including those showing a similar immunohistochemical staining in the three groups of specimens studied, the Western blot analysis showed differences in the banding pattern among normal, hyperplastic, and carcinomatous prostates. Present results suggest that the glycosylation of proteins was modified in both BPH and prostatic carcinoma. In BPH a strong expression of N-acetylgalactosamine residues occurred, while in prostatic carcinoma an increase of sialic acid, galactose and fucose residues was observed. No changes in mannose residues were detected.

Adult↗

The role of the androgen receptor in the development of prostatic hyperplasia and prostate cancer.

The androgen receptor (AR) is an androgen-inducible transcription factor characterized by a modular primary structure, with each module representing a distinct functional unit. After its interaction with androgens, the cytoplasmic AR is activated and translocated to the nucleus where it binds to target genes at the androgen responsive element(s) and recruits coregulators to form a multiprotein complex that interacts with transcriptional mediators and the basal transcription machinery to regulate gene transcription. Androgens play an essential role in the morphogenesis and physiology of the normal prostate. The etiology of benign prostatic hyperplasia (BPH) and prostatic neoplasia, which can progress to adenocarcinoma, is androgen-dependent, and reduction/obliteration of androgen action in the prostate has been the therapy of choice for BPH and prostate cancer. After androgen withdrawal and antiandrogen treatment, the androgen responsive prostate cancer cells cease to proliferate and undergo apoptosis, causing tumor regression. However, relapses are seen invariably, when tumors emerge as androgen-independent and apoptosis-resistant. Gene amplification and amino acid substitutions in the AR are detected at a high frequency in recurrent tumors. These changes confer growth advantage to the tumor cells due to either hypersensitivity of AR to low, castrate-level androgens or a realignment of the receptor conformation, leading to altered ligand specificity that enables antiandrogens, adrenal androgens and non-androgen steroids act agonistically to increase AR activity. Persistence of signaling by the wild-type AR in therapy-resistant tumors is due to the increased receptor activity caused by cross talk of AR with multiple intracellular signaling cascades, especially the growth factor activated MAP kinase/ERK and PI3 kinase/Akt pathways. Ablation of AR function using antisense oligodeoxynucleotides, ribozymes or small interference RNAs (RNAi) holds promise as future approaches to the successful treatment of hormone-refractory, apoptosis-resistant prostate tumors.

Adenocarcinoma↗

Aromatase mRNA levels in benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Estrogens are suspected to play a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. In this study, the expression of aromatase messenger ribonucleic acid (mRNA) was determined, and these levels were quantitated, in human prostatic tissues to evaluate the role of estrogens in the pathogenesis of BPH and prostate cancer. METHODS: Prostatic tissues were obtained either by retropubic prostatectomy, radical prostatectomy, or radical cystectomy from patients with BPH, prostate cancer, and bladder cancer. The expression of aromatase mRNA in the prostatic tissues was studied by Southern blot analysis of the reverse transcription and polymerase chain reaction technique (RT-PCR) products. Aromatase mRNA levels were measured in human prostatic tissues by the RT-PCR using a fluorescent primer. RESULTS: Aromatase mRNA was identified in all specimens by Southern blot analysis of the RT-PCR products. The concentrations of aromatase mRNA (mean +/- SD) which were measured by fluorometric quantitation in 16 of 19 patients with BPH and in 3 of 4 patients with prostate cancer, were 1.81 +/- 3.02, and 0.84 +/- 0.27, x 10(-3) attomoles/micrograms of total RNA, respectively. CONCLUSIONS: These results demonstrate local formation of estrogen in the prostates of patients with BPH and prostate cancer. Controlled studies will be necessary to determine whether this may be a factor in the development of BPH and prostate cancer.

Aged↗

The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer.

OBJECTIVE: To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS: The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS: Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS: TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.

Humans↗

Comparison of the clinical value of complexed PSA and total PSA in the discrimination between benign prostatic hyperplasia and prostate cancer.

BACKGROUND: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. METHODS: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves. RESULTS: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively. CONCLUSIONS: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionable.

Diagnosis, Differential↗

Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer?

BACKGROUND: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except alpha(2)-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. RESULTS: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P <0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 microg/L (areas under the curve, 0.851 vs 0.838). CONCLUSIONS: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.

Adult↗

Practice patterns of Canadian urologists in benign prostatic hyperplasia and prostate cancer. Canadian Prostate Health Council.

PURPOSE: We reviewed the practice patterns of Canadian urologists in benign prostatic hyperplasia (BPH) and prostate cancer, and assessed the changes that occurred between 1995 and 1998. MATERIALS AND METHODS: In 1995 and 1998 questionnaires were mailed to all active members of the Canadian Urological Association who practiced adult urology in Canada. Many questions were similar, allowing for the assessment of changes in practice patterns. RESULTS: A number of changes were observed between 1995 and 1998. Cystoscopy and imaging of the upper urinary tract were used less often to evaluate uncomplicated cases of BPH. However, 39% of respondents continued to perform cystoscopy routinely. Finasteride was no longer administered in men with a smaller prostate. In 1998 before radical prostatectomy 28% of respondents routinely performed a bone scan, 29% cystoscopy and 57% chest x-ray. The number believing that maximal androgen blockade is the most effective hormonal therapy decreased from 90% to 62%, while 24% reported in the 1998 survey that they frequently administered intermittent hormonal therapy. Comparison with an American study from 1995 indicated that American urologists used the American Urological Association symptom score and performed a prostate specific antigen test more frequently than Canadian urologists. However, Canadian urologists performed cystoscopy more frequently. CONCLUSIONS: These surveys provide a useful insight into the variations in clinical practice of Canadian urologists and help to determine whether changes are occurring in regard to the development of practice guidelines. They also indicate the need to develop further guidelines, and ensure that these guidelines are widely promoted and accepted by the urological community.

Adult↗

Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China.

OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.

China↗

Free to complexed PSA ratio in differentiating benign prostate hyperplasia from prostate cancer.

BACKGROUND: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.

Diagnosis, Differential↗

Serum sialic acid and prostate-specific antigen in differential diagnosis of benign prostate hyperplasia and prostate cancer.

In order to improve the diagnostic accuracy of the serum total and free prostate-specific antigen (PSA) in differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer, the serum total sialic acid (TSA) was measured and logistic regression (LR) models were built. Significantly higher serum PSA (p<0.001) concentrations were observed in patients with prostate cancer compared to control subjects, but no statistically significant differences were found in serum TSA concentrations between these groups. Serum PSA reliably discriminated patients with prostate cancer from control subjects, the area under the ROC curve (AUC) being 0.991 (0.010). When serum PSA was in the gray zone, from 4 to 10 microg/l, the diagnostic accuracy of PSA in discriminating patients with prostate cancer from BPH patients was very poor, AUC being 0.563 (0.132). However, using the same set of patients the LR model combining serum PSA, free to total PSA ratio and TSA values, as well as digital rectal examination results, had good diagnostic accuracy in discriminating the prostate cancer patients from patients with BPH, the area under the ROC curve being 0.895 (0.054). The present data suggest that the logistic regression model combining laboratory measurements and results of the clinical examination may be a useful adjunct in the differential diagnosis of benign and malignant prostate disease.

Biomarkers, Tumor↗

[Comparison of PSAD and PSAD-TZ value in prostatic hyperplasia and prostatic cancer].

OBJECTIVES: To compare PSAD, PSAD-TZ, PSA, FPSA/TPSA detection used in diagnosis of prostatic hyperplasia(BPH) and prostatic cancer(PCa). METHODS: Fourty-three cases of BPH and twenty cases of PCa with PSA < 20 micrograms/L were chosen, then compared PSA, PSAD, FPSA/TPSA, PSAD-TZ between BPH and PCa. RESULTS: The mean PSA in BPH and PCa is (10.47 +/- 6.25) microgram/L and (13.92 +/- 3.20) microgram/L respectively with no statistic difference (P > 0.05). The mean PSAD in BPH and PCa is (0.15 +/- 0.12) microgram/L and (0.24 +/- 0.13) microgram/L respectively with statistic difference (P < 0.05). The mean FPSA/TPSA in BPH and PCa is (0.58 +/- 0.42) microgram/L and (0.26 +/- 0.17) microgram/L respectively with statistic difference (P < 0.05). The mean PSA-TZ in BPH and PCa is (0.26 +/- 0.22) and (0.51 +/- 0.28) respectively with obviously statistic difference (P < 0.01). CONCLUSIONS: The results suggest PSAD, FPSA/TPSA, especially PSAD-TZ could be used to distinguish BPH and PCa.

Aged↗

[Expression and significance of clusterin in normal prostate, benign prostate hyperplasia and prostate cancer].

OBJECTIVE: To investigate the expression and significance of Clusterin in normal prostate, benign prostate hyperplasia (BPH) and prostate cancer. METHODS: Clusterin expression in samples of 12 normal prostate, 15 BPH, and 56 prostate cancer were studied by immunohistochemical stain. RESULTS: Of 83 cases, 67 are positive or weak positive (81%). The rate of positive or weak positive for normal prostate, BPH and prostate cancer was 17% (2/12), 73% (11/15), and 96% (54/56) respectively. The expression level of Clusterin in prostate cancer was much higher than in normal prostate (t = 8.82, P < 0.01). BPH (t = 7.63, P < 0.01) was related positively with pathological grade (r = 0.649, P < 0.01) and stage (r = 0.609, P < 0.01) of prostate cancer. CONCLUSION: Clusterin may play an important role in the biological characteristics of prostate cancer by the anti-apoptosis pathway.

Apoptosis↗

[Tumor infiltrating dendritic cells and Mucin1 gene expression in benign prostatic hyperplasia and prostate cancer].

OBJECTIVE: To study the expression of Mucin1 gene and tumor infiltrating dendritic cells(TIDC) in the tissues of benign prostatic hyperplasia (BPH) and prostate cancer. METHODS: Mucin1 and TIDC were detected in 20 specimens of BPH and 30 specimens of prostate cancer by immunohistochemistry SP method. RESULTS: MUC1 expressed in both prostate cancer and BPH. The staining patterns were significantly associated with tumor pathological grade (P < 0.001). The number of TIDC was negatively correlated with tumor pathological grade, the higher the grade, the smaller the number of TIDC (P < 0.001). CONCLUSIONS: The expression pattern of MUC1 and the number of TIDC could be considered as useful markers to evaluate the malignant degree and prognosis of prostate cancer. The decrease of TIDC plays an important role in tumor immune evasion and immune tolerance. Highly expressed MUC1 could lead to the failure of hormonal treatment for prostate cancer, and contribute much to tumor infiltration and metastasis.

Antigens, Neoplasm↗

[Further studies on the relationship between benign prostatic hyperplasia and prostatitis].

Benign prostatic hyperplasia(BPH) and prostatitis are two common diseases in aging men. In recent years, the study of correlation between these two diseases has been paid more and more attention to. Some researchers presumed that inflammation is one of the most important causations of BPH, however, it is not profound enough on this etiologic hypothesis at present. The writer, on the base of his clinical experiences, dissertated the etiology of BPH, the pathologic figures of coexistence of BPH and prostatitis, and the presumption of inflammation promoting BPH on the molecular biology level. We hope our colleagues pay attention to this problem, and do more study on it.

Humans↗

[Expression and its significance of b-FGF in human benign prostatic hyperplasia and prostatic carcinoma tissues].

AIM: To investigate the clinical significance of basic fibroblast growth factor (b-FGF) in human benign prostatic hyperplasia (BPH) and prostatic carcinoma (Pca). METHODS: b-FGF expressions were examined by RNA dot blot hybridization and immunohistochemical staining in prostate tissues from 40 normal cases (NP), 38 BPH and 36 Pca. RESULTS: The expressions of b-FGF in BPH and Pca tissues were significantly higher than those in normal prostate tissues (P < 0.01). There was no significant correlation between the increased expression of b-FGF and the graduation of BPH, pathologic grading as well as clinical stages of Pca. CONCLUSION: b-FGF may be secreted from BPH and Pca tissues themselves, which is closely involved in the genesis and development of BPH and Pca.

Aged↗

[Analysis of the differences in the expression of HSP27 and c-kit between benign prostatic hyperplasia and prostatic cancer tissues].

OBJECTIVE: To examine the differences in the expression of HSP27 and c-kit between benign prostatic hyperplasia (BPH) and prostatic cancer (PCa) tissues and to analyse the relationship between their expression and BPH and PCa, especially the relationship with the occurrence, development, prognosis and treatment of PCa. METHODS: An immunohistochemical staining (SP method) for HSP27 and c-kit was undertaken on 40 BPH and 40 PCa tissues samples. RESULTS: Consistent patterns of cytoplasmic staining for HSP27 were seen in all sections of tissue from BPH. The glandular epithelium stained very strongly positively and the stroma stained positively. The staining for HSP27 in PCa tissues was located in the cytoplasm of glandular epithelia, but the expression of HSP27 in PCa was higher than BPH (P < 0.05). The staining for c-kit in BPH tissues was located in the cytoplasm of smooth muscle cells, and in PCa tissues was located in epithelial cells. The expression of c-kit in PCa tissues was lower than BPH (P < 0.05). The expression level of both HSP27 and c-kit were decreased with the development of grade of PCa (P < 0.05); HSP27 was increased with the development of clinical stage of PCa (P < 0.05 ); c-kit was decreased with the development of clinical stage of PCa (P < 0.05). CONCLUSION: The expression level of HSP27 and c-kit was highly correlated with the process of the development from BPH to PCa, and also correlated with tumor grades and stages. The expression of HSP27 and c-kit may be used as an important pathological index and may be helpful for the treatment of PCa.

Aged↗

Apoptosis-related gene expression in benign prostatic hyperplasia and prostate carcinoma.

BACKGROUND: The aim of this study was to examine the expressions of the bcl-2, bax, fas and c-myc apoptosis-related genes in benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) to determine whether significant differences exist within each disease and between the two groups of patients. The correlation between gene expression and tumour diameter, stage, Gleason score and serum PSA was also investigated. PATIENTS AND METHODS: Tissue specimens from 51 cases of BPH and 27 cases of CaP were examined for bcl-2, bax, fas and c-myc expression by reverse transcriptase-PCR (RT-PCR). RESULTS: In BPH, bcl-2 and bax gave the weakest signals (p < 0.001). In CaP, bcl-2 was the least expressed gene (p < 0.001). In both patient groups, fas and c-myc were the most highly expressed genes (p < 0.05). Both bcl-2 and bax were expressed at higher levels in CaP than in BPH (p < 0.02). The bcl-2/bax ratio was lower in CaP than in BPH (p < 0.001). Bcl-2 was more highly expressed in high Gleason grade (> 7) tumours (p < 0.05). In the BPH group, bax showed a positive relationship with fas (p < 0.01), while the bcl-2 level inversely correlated with that of c-myc (p < 0.05). CONCLUSION: Our data showed that all the apoptosis-related genes were expressed in both BPH and CaP. The stronger expression of bax and the lower bcl-2/bax ratio observed in CaP may suggest a pro-apoptotic stimulus, while the higher bcl-2 levels appear to counterbalance the tendency to cell death.

Aged↗

[Expression of nucleosomal binding protein 1 in normal prostate benign prostate hyperplasia, and prostate cancer and significance thereof].

OBJECTIVE: To investigate the expression of nucleosomal binding protein 1 (NSBP1) in normal prostate (NP), benign prostate hyperplasia (BPH), and prostate cancer (PCa) and significance thereof. METHODS: Western blotting was used to detect the expression of NSBP1 in 10 specimens of NP from voluntary donors who died of accidents, and 15 specimens of PCa resected during operation. Immunohistochemistry was used to detect the NSBP1 expression in 19 specimens of NP resected during complete cystectomy from patients with bladder carcinoma, and 26 specimens of BPH and 40 specimens of PCa, all resected during operation. RESULTS: Western blotting showed that the relative optical density (OD) of NSBP1 in the PCa tissue was 0.66 +/- 0.02, significantly higher than that of the NP tissue (0.26 +/- 0.03, t = 37.308, P < 0.01). Immunohistochemistry showed that the positive and weak positive rates of protein expression of NSBP1 in the PCa tissue was 80.0% (32/40), significantly higher than those of the NP tissue (36.8%, 7/19) and BPH (34.6%, 9/26) (t = -3.569 and t = -4.152, both P < 0.01). The NSBP1 expression level in the PCa tissue was not correlated with the pathological staging, grade, and serum prostate-specific antigen (P = 0.911, 0.666, and 0.779). CONCLUSION: Highly expressed in the PCa tissue, NSBP1 protein is may be involved in the carcinogenesis of PCa.

Adult↗