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[Determination of free prostatic specific antigen cut point for the selection of patients in first prostate biopsy].

OBJECTIVES: Determine the cut point of free PSA rate for optimize the first prostate biopsy indication. MATERIAL AND METHODS: Prospective trial between june 2002-september 2004, We included patients in first prostate biopsy with normal rectal digital examen, total PSA between 3-10 ng/ml and normal transrectal prostate ultrasound. We realize descriptive stadistic analisis of variables age, total PSA, prostate volume and % free PSA and analitic stadistic analisis with ROC curves of variables total PSA and % free PSA for determine as of her predicts the best one rate of prostate cancer. RESULTS: We reclute 727 men with a mean age 62.91 years, total PSA mean 6.12 ng/ml, prostate volume mean 42.78 cc and % free PSA mean 15.22%. We had 106 prostate cancer, the prostate cancer rate in first biopsy was 14.6%; 77 cases had 1 lobe prostate cancer and 29 in 2 lobes. The most frecuent gleason was 6 (46 cases 43.4%) and the second gleason 7 (43 cases 40.6%). In the ROC curves analysis, total PSA had area under the curve 0.476 (p=0.3) and 0.611 (p=0.023) for % free PSA. The optime cut point for % free PSA in our trial was 19% (Sensibility 91.4% and Specificity 20%). The use of this cut point had allowed the saving us 138 biopsies (19.11%) with the lost one of diagnose of 10 cases of cancer of prostate. CONCLUSIONS: The use of the % free PSA is useful and allows in our region the best indication of the patients who are going to first biopsy of prostate, avoiding the accomplishment of unnecessary biopsies.

Biopsy↗

Immunohistochemical labelling for prostate specific antigen in non-prostatic tissues.

Immunohistochemical detection of prostate specific antigen (PSA) in metastases of adenocarcinomas is widely used as an aid to identify the prostatic origin of metastatic cells. However, on the one hand, PSA may not be expressed in some poorly differentiated prostatic carcinomas, while on the other, PSA immunoreactivity has been found in small amounts in non-prostatic tissues. The aim of the current study was to evaluate the prevalence of PSA immunoreactivity in normal non-prostatic tissues and in breast carcinoma. PSA was localized by immunohistochemistry with four commercial antibodies in 34 different normal human tissues, and in 15 ductal and seven apocrine breast carcinomas. Concentrations of PSA in tissue homogenates of prostate and nine non-prostatic tissues from autopsied subjects were measured by a two-site immunoradiometric assay. Weak PSA immunoreactivity was found by immunohistochemistry in kidney, parotid gland and pancreatic tissues. Variable PSA immunoreactivity was seen in three cases of ductal (20%) and two cases of apocrine breast carcinoma (28%). No consistent PSA immunoreactivity was found in homogenates of non-prostatic tissues by the immunoradiometric assay. We conclude that PSA is a quite specific marker of prostatic tissue. However, there are some non-prostatic neoplastic and normal tissues that express PSA. Therefore, a definite diagnosis of metastasis of prostatic origin cannot be made on the basis of immunolabelling for PSA alone.

Antibodies, Neoplasm↗

Prostate activity and prostate cancer in spinal cord injury.

In addition to androgen, autonomic nerves may be involved in prostatic function. As patients with spinal cord injury (SCI) have impaired innervation of the prostate, the prostate volume and prostate-specific antigen (PSA) level in patients with SCI may be different from those of healthy men. Experiments in rats with SCI indicate that neurogenic factors play an important role in prostate growth and function but the same phenomena may not occur in men with SCI because the current animal models differ from clinical results in humans in several respects. Although many of studies indicate the importance of intact peripheral innervation on the secretory function of the prostate, the effect of more central denervation such as occurs in complete SCI at the cervical, thoracic, or lumbar levels on prostatic function is unclear. In addition, the impact of central nervous system injury on prostatic secretory activity, and consequently on serum PSA levels, is also not clear. Furthermore, the impact of hormonal changes on prostate cancer development and prognosis observed in patients with SCI may also be affected by the level of injury and patient age at the time of injury, which have not been studied. In this article, we review prostate activity and prostate cancer in SCI and discuss how they may relate to neurogenic factors.

Adolescent↗

New simple method of transabdominal ultrasound to assess the degree of benign prostatic obstruction: size and horizontal shape of the prostate.

BACKGROUND: Transabdominal ultrasound has been the standard clinical tool for evaluating prostatic size; however, the severity of benign prostatic obstruction does not always correspond to the size of the prostate. The purpose of this study was to consider the utility of two parameters, (i) the prostatic volume (Pvol) and (ii) the ratio of the height : width of the maximum horizontal section of prostate (H : W) obtained by transabdominal ultrasound, in screening the degree of benign prostatic obstruction. The results were compared with the linear passive urethral resistance relation (lin-PURR) obtained by pressure-flow studies. METHODS: Fifty-one men with lower urinary tract symptoms were prospectively evaluated in regard to urodynamic parameters, transabdominal ultrasound volume of the prostate, and calculation of lin-PURR. RESULTS: A significant positive correlation was found between Pvol and the degree of benign prostatic obstruction. When the ultrasonographic parameters of greater than 30 mL Pvol and 0.8 H : W were adopted as provisional cut-off points for detecting patients with obstruction, the selected 10 cases had lin-PURR > 3. In addition, there were six cases classified with lin-PURR >or= 3 despite the fact that their Pvol was less than 30 mL. Their H : W values were > 0.8. CONCLUSIONS: Transabdominal ultrasound is useful as a screening test for evaluating the prostate. In addition to the size of the prostate, the parameter of the horizontal shape (H : W ratio) makes an assessment of the degree of benign prostatic obstruction more reliable.

Aged↗

Abnormal prostatic cells in ejaculates from men with prostatic cancer--a preliminary report.

OBJECTIVE: To relate findings from a novel approach, ejaculate cytology, to the established reference, histopathology from transrectal ultrasonography (TRUS)-guided prostatic biopsies, in patients at risk of having prostatic cancer on the basis of an abnormal digital rectal examination (DRE) and/or an elevated serum prostate specific antigen (PSA). PATIENTS SUBJECTS AND METHODS: Thirty-seven men suspected of having prostatic carcinoma provided ejaculate specimens which were collected in Hanks solution. The specimens were centrifuged to form a pellet from which smears were made for cytological examination. Immunohistochemical staining for PSA and prostatic acid phosphatase (PAP) were performed on embedded blocks of these cells. TRUS-guided sextant biopsies were performed for histological specimens using standard clinical procedures. A control group of 32 men < 30 years of age, with no family history of prostatic cancer, also produced specimens of ejaculate which were processed similarly. RESULTS: Frankly malignant and atypical prostatic cells were identified in ejaculate specimens from 14 of the 37 patients. Of 12 patients with TRUS biopsies positive for malignancy, nine (75%) had abnormal cells in their ejaculates. Furthermore, five of 25 patients with negative biopsies for adenocarcinoma also had abnormal ejaculate cytology; two of these five patients had high-grade prostatic intra-epithelial neoplasia (PIN). In the control group, no PSA- or PAP-positive prostatic epithelial cells were identified. Normal prostatic cells were not seen in any of the ejaculate specimens examined. CONCLUSIONS: These results indicate that ejaculate cytology, which is a non-invasive and easily repeated investigation, may prove to be a useful approach in the early detection of cancer of the prostate. However, its value in this role, together with the clinical significance of cytological findings, needs to be established, especially in relation to PSA and TRUS biopsy.

Acid Phosphatase↗

Immunohistochemical evaluation of proliferating cell nuclear antigen, prostate-specific antigen and alpha 1-antichymotrypsin in human prostate cancer.

OBJECTIVE: To determine the relationship between growth fractions defined by proliferating cell nuclear antigen (PCNA), prostate-specific antigen (PSA) and alpha 1-antichymotrypsin (ACT) staining in prostate cancer. MATERIALS AND METHODS: A total of 96 lesions, including 71 from prostate cancers and 25 from benign prostatic hyperplasia (BPH) were evaluated in microscopic sections of the prostatic tissues from 34 patients with prostate cancer. Immunohistochemical staining was performed with an avidin-biotin system using monoclonal anti-PCNA antibodies, polyclonal anti-PSA and anti-ACT antibodies. RESULTS: There was a significant difference in the mean PCNA labelling index between tissue from prostate cancer (4.2 +/- 7.1) and BPH (0.5 +/- 1.1) (P = 0.002). The mean labelling index of PCNA tended to increase with increasing Gleason score. The proportion of cells positive for PSA was significantly higher in tissue from BPH than from prostate cancer (P = 0.005). While the proportion of cells immunostaining for ACT was significantly higher in tissue from BPH compared to that from prostate cancer (P = 0.02), there was no significant difference in the proportion of ACT-positive cells among prostate cancers of differing Gleason score. The mean labelling index of PCNA decreased significantly with the increase in the proportion of PSA-positive cells (P = 0.013). There was a significant relationship between the proportion of ACT- and PSA-positive cells (P = 0.001). CONCLUSION: These results indicate a reciprocal relationship between cell growth and tumour differentiation in prostate cancer. Although the significance of ACT deserves further study, there was evidence for the complexing of PSA with ACT from the immunohistochemical studies.

Humans↗

The value of endotoxin concentrations in expressed prostatic secretions for the diagnosis and classification of chronic prostatitis.

OBJECTIVE: To clarify the value of endotoxin concentrations in expressed prostatic secretions (EPS) in the diagnosis and classification of chronic prostatitis. PATIENTS, SUBJECTS AND METHODS: The study included 88 consecutive patients with chronic prostatitis and 15 controls with no urological disease. The diagnosis and classification were based on a history, symptoms, a digital rectal examination of the prostate, and a white blood cell count in the EPS. Endotoxin concentrations in the EPS or urine were measured using a colorimetric assay and standard microbiological methods used to identify bacterial growth. RESULTS: In men with chronic prostatitis caused by Gram-negative or combined Gram-negative and -positive bacteria, the endotoxin levels in urine collected immediately after prostatic massage were significantly greater (P < 0.01) than in a midstream urine sample, and the concentration in the EPS was significantly higher (P < 0.05) than that in the control group. The same was true of patients with chronic prostatitis and Gram-positive bacteria isolated from the EPS or urine after massage. In patients with chronic pelvic pain syndrome (grade IIIA) the endotoxin level in the urine after massage was also significantly higher (P < 0.05) than that of the midstream sample, but there was no significant difference between the concentration in these samples in patients with grade IIIB, and no significant difference between the endotoxin concentration of the EPS in patients with grade IIIB and that in controls. CONCLUSION: Endotoxin concentrations are increased in the EPS or urine (after prostatic massage) of men with bacterial chronic prostatitis or chronic pelvic pain syndrome grade IIIA. The current routine examinations (including bacterial culture and routine examination of EPS or urine) before diagnosis and classification of chronic prostatitis are insufficient to describe the cause and pathogenesis of this condition. The endotoxin concentration of the EPS or urine after massage may provide a supplementary tool to identify the cause of chronic prostatitis.

Adult↗

Assessing the vascular-stromal coefficient in patients with benign prostatic hyperplasia or prostate cancer using transrectal ultrasonography and power Doppler analysis.

OBJECTIVES: To assess a coefficient of the prostatic blood supply in patients with prostate cancer or benign prostatic hyperplasia (BPH), and thus improve the diagnostic and prognostic variables needed to evaluate patients with prostate cancer. PATIENTS AND METHODS: The vascular-stromal coefficient was defined as the ratio of the blood vessel surface area and the surface area of the prostate, using power Doppler functions and transrectal ultrasonography. The index was calculated for the plane of the prostatic surface from the apex to the widest points of the peripheral zone, and for the plane across the highest density of blood vessels in the transition zone. A micobubble contrast agent was used to intensify the acoustic signals from prostatic vessels. The images were reconstructed in three dimensions. In all, 61 patients with BPH and 32 with confirmed prostate cancer were examined, and compared with a control group of young men. RESULTS: In the horizontal plane crossing the apex of the prostate, the vascular-stromal coefficient was 0.0054 for the controls, 0.0072 for BPH and 0.0067 for cancer. At the level of the highest density of blood vessels the respective values were 0.0083, 0.038 and 0.029. The respective values for the first plane after using the contrast agent were 0.025, 0.092 and 0.0365, and in the second level 0.04, 0.15 and 0.14. CONCLUSION: The vascular-stromal coefficient measured at both levels was higher in patients with BPH than in those with cancer or than in the controls. The prostatic vascular system can be computer-reconstructed in three dimensions, allowing an evaluation of asymmetry and other vascular abnormalities. The contrast agent effectively increases the vascular acoustic signals from the prostate, enhancing by a factor of five the visualization of blood vessels when using the power Doppler option.

Aged↗

Prostate cancer vs hyperplasia: relationships with prostatic and adipose tissue fatty acid composition.

The objective of the present study was to study whether adipose tissue and prostatic tissue fatty acid composition differentiates between prostate cancer and benign hyperplasia patients. In addition, the present investigation aimed at exploring the extent to which prostatic tissue fatty acid composition differentiates between prostate-confined cancer and extraprostatic disease including possible metastasis. The subjects were 71 male patients from the island of Crete. Half the patients (n=35) had been diagnosed with benign hyperplasia of the prostate, half with prostatic malignancy (n=36). Patients were examined at the outpatient clinic of the urology unit, University Hospital, Medical School, University of Crete. Relative to benign hyperplasia patients, cancer patients had elevated adipose tissue saturated and reduced monounsaturated fatty acid levels. Cancer patients had reduced prostate tissue stearic to oleic acid ratios and stearic acid levels as opposed to hyperplasia patients. The most pronounced difference between cancer patients and hyperplasia patients was a 3-fold elevated prostatic palmitoleic acid in the former group. Relative to benign hyperplasia patients, cancer patients had reduced prostate tissue arachidonic and docosahexaenoic acid levels. Finally, there was a significantly reduced omega-3/omega-6 polyunsaturated fatty acid ratio in the prostate cancer patient as opposed to the benign hyperplasia group. The pronounced elevations in prostatic tissue palmitoleic acid in cancer patients highlight a possible role of this fatty acid in neoplastic processes. The decreased arachidonic acid levels in cancer patients possibly stem from enhanced metabolism of arachidonic acid via lipoxygenase and cyclooxygenase pathways, and the formation of derivatives such as 5-HETE, 15-HETE, 12(S)-HETE and PGE(2).

Adipose Tissue↗

Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer.

The identification of cell surface antigens is critical to the development of new diagnostic and therapeutic modalities for the management of prostate cancer. Prostate stem cell antigen (PSCA) is a prostate-specific gene with 30% homology to stem cell antigen 2, a member of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA encodes a 123-aa protein with an amino-terminal signal sequence, a carboxyl-terminal GPI-anchoring sequence, and multiple N-glycosylation sites. PSCA mRNA expression is prostate-specific in normal male tissues and is highly up-regulated in both androgen-dependent and -independent prostate cancer xenografts. In situ mRNA analysis localizes PSCA expression in normal prostate to the basal cell epithelium, the putative stem cell compartment of the prostate. There is moderate to strong PSCA expression in 111 of 126 (88%) prostate cancer specimens examined by in situ analysis, including high-grade prostatic intraepithelial neoplasia and androgen-dependent and androgen-independent tumors. Flow cytometric analysis demonstrates that PSCA is expressed predominantly on the cell surface and is anchored by a GPI linkage. Fluorescent in situ hybridization analysis localizes the PSCA gene to chromosome 8q24.2, a region of allelic gain in more than 80% of prostate cancers. A mouse homologue with 70% amino acid identity and similar genomic organization to human PSCA has also been identified. These results support PSCA as a target for prostate cancer diagnosis and therapy.

Amino Acid Sequence↗

PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression.

Prostate cancer, the most frequent solid cancer in older men, is a leading cause of cancer deaths. Although proliferation and differentiation of normal prostate epithelia and the initial growth of prostate cancer cells are androgen-dependent, prostate cancers ultimately become androgen-independent and refractory to hormone therapy. The prostate-specific antigen (PSA) gene has been widely used as a diagnostic indicator for androgen-dependent and -independent prostate cancer. Androgen-induced and prostate epithelium-specific PSA expression is regulated by a proximal promoter and an upstream enhancer via several androgen receptor binding sites. However, little progress has been made in identifying androgen-independent regulatory elements involved in PSA gene regulation. We report the isolation of a novel, prostate epithelium-specific Ets transcription factor, PDEF (prostate-derived Ets factor), that among the Ets family uniquely prefers binding to a GGAT rather than a GGAA core. PDEF acts as an androgen-independent transcriptional activator of the PSA promoter. PDEF also directly interacts with the DNA binding domain of androgen receptor and enhances androgen-mediated activation of the PSA promoter. Our results, as well as the critical roles of other Ets factors in cellular differentiation and tumorigenesis, strongly suggest that PDEF is an important regulator of prostate gland and/or prostate cancer development.

Amino Acid Sequence↗

Men's attitudes toward prostate cancer and seeking prostate-specific antigen testing.

BACKGROUND: Although the Australian Cancer Society recommends against performing PSA tests to screen for prostate cancer, many Australian men currently undergo such screening. This study investigated attitudinal variables that may predict prostate cancer screening behaviors in this context. METHODS: A questionnaire was administered by mail in a two-phase procedure, first to a sample of 1,461 men (46% response), then to 919 men from the initial sample. Prostate cancer screening behaviors of men > 40 years old were examined. The questionnaire assessed worry about prostate cancer, perceived vulnerability to prostate cancer, belief in the efficacy of PSA testing for detection, having received a PSA test for detection, and the presence of urologic symptoms at the time of testing. RESULTS: Men who had had PSA testing with urologic symptoms at the time of the test were more worried about prostate cancer and perceived themselves as more vulnerable to prostate cancer compared with both asymptomatic tested and untested men. Men who had undergone PSA testing believed the test to be more effective in the detection of prostate cancer than did men who had not. CONCLUSIONS: Urologic symptoms act as a risk cue for men to prostate cancer. Asymptomatic men should be considered separately from symptomatic men in the investigation of psychological variables predictive of seeking screening for prostate cancer. These findings are discussed in terms of both the focus and design of interventions to alter prostate cancer screening behavior and their implications for the clinical management of men with urologic symptoms.

Adult↗

The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D.

The hormonal form of vitamin D, 1 alpha,25-dihydroxyvitamin D [1 alpha,25(OH)(2)D] promotes the differentiation and inhibits the proliferation, invasiveness and metastasis of prostate cells. However, 1 alpha,25(OH)(2)D is not suitable as a chemopreventive agent because its administration can cause hypercalcemia. Serum levels of 1 alpha,25(OH)(2)D are tightly regulated by the renal enzyme, 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase), which synthesizes 1 alpha,25(OH)(2)D from the prohormone, 25-hydroxyvitamin D [25(OH)D]. Normal prostate epithelial cells in primary culture, as well as several prostate cancer cell lines, also express 1 alpha-OHase and synthesize the hormone intracellularly. We now investigated the regulation of the prostate 1 alpha-OHase by the three most important regulators of the renal 1 alpha-OHase: calcium, 1 alpha,25(OH)(2)D and parathyroid hormone (PTH). The 1 alpha-OHase activity in the primary cultures of prostate epithelial cells was inhibited by 1 alpha,25(OH)(2)D(3) at 10 and 100 nM, whereas PTH at 10 and 100 nM had no significant effect. Calcium at 1.2 and 2.4 mM had no significant effect on the enzyme activity in the PZ-HPV-7 cell line, a prostate epithelial cell line derived from normal prostate tissue. Conversely, 1.2 or 2.4 mM calcium markedly inhibited 1 alpha-OHase activity in a human kidney cell line used as a positive control. Furthermore, PTH at 100 nM and calcium at 1.2 and 2.4 mM had no effect on the 1 alpha-OHase gene promoter activity in prostate cells, whereas the promoter activity was inhibited 48 +/- 5% by 100 nM 1 alpha,25(OH)(2)D(3). Our findings suggest that, unlike the renal enzyme, the prostate 1 alpha-OHase appears to be largely unregulated by serum levels of PTH and calcium. These findings support the hypothesis that vitamin D or 25(OH)D may be useful as chemopreventive agents for prostate cancer because their administration should cause an increased synthesis of 1 alpha,25(OH)(2)D within prostate cells.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Screening for prostate cancer using prostate-specific antigen alone as a first-line checkup parameter: results of the health checkup system.

BACKGROUND: The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS: Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS: Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS: These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

Aged↗

Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer.

BACKGROUND: Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells. METHODS: We coupled a chemically modified form of thapsigargin, L12ADT, to a peptide carrier that is a substrate for the prostate-specific antigen (PSA) protease to produce a soluble, cell-impermeant latent prodrug that is specifically activated extracellularly within metastatic prostate cancer sites by PSA. We analyzed the kinetics of PSA hydrolysis of the prodrug, the in vitro cytotoxicity of the prodrug against PSA-producing LNCaP human prostate cancer and PSA non-producing HCT-116 human colon cancer cells, and the in vivo pharmacokinetics of the prodrug in mice. We also analyzed antitumor efficacy of the prodrug in nude mice xenograft models of prostate cancer (using LNCaP cells) and renal carcinoma (using human SN12C cells). RESULTS: The L12ADT peptide prodrug was hydrolyzed efficiently by PSA, was selectively toxic to PSA-producing prostate cancer cells in vitro, and was stable in human plasma. A single dose of 7 mg/kg resulted in a peak serum prodrug concentration of 15.4 +/- 1.1 microM and a half-life of approximately 2.8 hours. Over 24 hours, less than 0.5% of free L12ADT was observed in plasma. Levels of prodrug and liberated L12ADT in prostate cancer xenograft tumors were approximately eightfold and sixfold, respectively, higher than the in vitro LD50s. Prostate cancer xenograft tumors in mice treated with prodrug by intravenous administration were growth-inhibited without substantial host toxicity. Continuous subcutaneous prodrug administration in mice produced complete growth inhibition of established PSA-producing prostate cancer xenograft tumors but had no effect on PSA non-producing renal carcinoma xenograft tumors. CONCLUSION: Further development of PSA-activated thapsigargin prodrugs as therapy for metastatic prostate cancer is warranted.

Animals↗

The impact of polymorphism on prostate specific antigen gene on the risk, tumor volume and pathological stage of prostate cancer.

PURPOSE: A single nucleotide polymorphism with adenine (A) to guanine (G) substitution is identified at position -158 in the androgen response elements region of the prostate specific antigen (PSA) gene. We evaluated the relationship between the PSA -158A/G polymorphism and the risk, tumor volume and pathological stage of prostate cancer. MATERIALS AND METHODS: Peripheral venous blood samples were obtained from 122 patients with prostate cancer and 84 controls with benign prostatic hyperplasia. The diagnosis, tumor volume and pathological stage of prostate cancer were all determined according to the pathological reports of transrectal ultrasound guided prostate biopsy, transurethral prostate resection and radical prostatectomy. The PSA -158A/G polymorphism was determined by polymerase chain reaction based restriction fragment length polymorphism methods. RESULTS: Patients with prostate cancer had significantly greater frequencies of the G allele (87.3% vs 77.4%) and GG genotype (78.7% vs 61.9%) than the control group (p = 0.008 and 0.028, respectively). The OR of GG to AG and AA was 2.27 (p = 0.008). In the prostate cancer group the GG genotype was also associated with larger tumor volume (2.34 vs 0.82 ml) and higher pathological stage (organ confined cancer 68.2% vs 31.8% and extracapsular extension 100% vs 0%) than the GA and AA genotypes (p = 0.013 and 0.036, respectively). CONCLUSIONS: The PSA -158A/G polymorphism is associated with prostate cancer. The G allele increases the risk of prostate cancer and the GG genotype is associated with larger tumor volume and higher pathological stage.

Aged↗

Distorted rectal tissue on prostate needle biopsy: a mimicker of prostate cancer.

Rectal tissue is often seen in needle biopsies of the prostate gland. On rare occasion distorted rectal glands can mimic prostatic adenocarcinoma, an issue not previously addressed in the peer-reviewed literature. We evaluated 16 prostate needle biopsies received in consultation where the submitting pathologist questioned whether a focus of rectal tissue was prostate cancer. In addition to the distorted architecture, features mimicking prostate cancer included: (1) blue-tinged intraluminal mucinous secretions in 10 cases (63%), (2) prominent nucleoli in 6 cases (37%), (3) mitotic activity in 6 cases (37%), (4) extracellular mucin in 5 cases (31%), and (5) adenomatous changes of the rectal tissue in 1 case (6%). Immunohistochemical results further mimicked prostate cancer with negative stains for the basal cell markers high-molecular weight cytokeratin (n=6) and p63 (n=4), and positive stains for racemase in 4 of 5 biopsies. Diagnostic clues to recognizing that these foci were distorted rectal fragments were the presence of (1) lamina propria in 12 cases (75%), (2) rectal tissue located on a detached fragment of tissue in 10 biopsies (63%), (3) associated inflammation in 10 cases (63%), (4) goblet cells in 7 cases (44%), and (5) muscularis propria in 6 cases (37%). In 2 cases, there was negative staining for prostate specific antigen (PSA) and in 1 case negative staining for cytokeratin 7 and positivity for cytokeratin 20. Rectal glands are associated with many of the classical features of prostate cancer, and immunohistochemistry may be misleading. Recognition of these features mimicking prostate cancer and awareness of other findings that are diagnostic of rectal tissue on biopsy can prevent a misdiagnosis of atypical prostate glands or prostate cancer.

Adenocarcinoma↗

Measurement of prostate specific antigen complexed to alpha1-antichymotrypsin to avoid unnecessary biopsy in patients with serum prostate specific antigen levels 4-20 ng/mL.

AIM: To investigate whether measuring prostate specific antigen complexed to alpha1-Antichymotrypsin (PSA-ACT) can increase sensitivity and specificity in detecting prostate cancer. METHODS: In this prospective study, we measured serum total PSA, PSA-ACT, free PSA, prostate volume and transition zone volume on 210 patients with total PSA level of 4-20 ng/mL. From fitted curves between positive predictive values for prostate cancer and age, prostate volume, transition zone volume, total PSA, PSA-ACT or F/T ratio, each function predicting prostate cancer was determined. Relative probabilities for prostate cancer (RPpca) which were defined by combined functions of age, F/T ratio, prostate volume or transition zone volume, and total PSA or PSA-ACT were calculated. Furthermore, using logistic regression, analysis was performed to determine the probability of prostate cancer. Receiver-operating characteristic analysis was performed to clarify the areas under the curve (AUC) for conventional single parameters, RPpca and logistic regression probability. RESULTS: F/T ratio showed the largest AUC among conventional parameters. The AUC of RPpca was larger than those of F/T ratio and logistic regression probability. RPpca using the functions of age, transition zone volume, PSA-ACT and F/T ratio showed the largest AUC and highest specificity at sensitivity 95% level, however, specificities at sensitivity 90% and 85% were identical to those of RPpca using the functions of age, prostate volume, total PSA and F/T ratio. CONCLUSIONS: RPpca using the functions of age, transition zone volume, PSA-ACT and F/T ratio was the best way to detect prostate cancer, however, the usefulness of PSA-ACT appears limited, considering the cost.

Aged↗