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At least 793 records · Page 44Linked to original sources
PubMed2005

Easy method of assessing volume of prostate adenocarcinoma from estimated tumor area: using prostate tissue density to bridge gap between percentage involvement and tumor volume.

AIM: To determine prostate carcinoma tumor volume in routine pathology practice by using prostate tissue density. METHODS: Prostate tissue density was determined experimentally by using picnometry in 57 unfixed prostate tissue fragments of different size. The percentage of prostate involvement was converted to tumor volume using the equation V=m/rho (g/mL). Additionally, all tumor foci were outlined in 46 prostates. A high grade component was also designated. The percent of prostate involvement by the tumor and separately by the high-grade component was determined using the fine grid method (0.9 mm resolution) in all cases. Pathologist's estimated square area method was applied for comparison in 27 cases. All tumor foci were evaluated for Gleason grades. RESULTS: Prostate tissue density (rho) was 0.98 or approximately 1.0 (g/mL). Quicker estimated square area method was fully comparable to more laborious fine grid method for determination of percent of prostate involvement. The percentage of prostate involvement by the tumor as measured by the grid method was not significantly associated with the Gleason sum of the tumor. However, the total tumor volume that was calculated from the percent tumor involvement, mass of the prostate, and tissue density was positively associated with the Gleason sum (P=0.035, linear-by-linear association). CONCLUSION: Our results show that prostate tissue density can be used to determine prostate carcinoma tumor volume in routine pathology practice.

Adenocarcinoma↗
PubMed2003

Prostate carcinoma risk subsequent to diagnosis of benign prostatic hyperplasia: a population-based cohort study in Sweden.

BACKGROUND: Pathologically, benign prostatic hyperplasia (BPH) is not considered a precursor for prostate carcinoma. However, because the two conditions share not only a similar hormonal environment within the prostate but also several common risk factors, it is possible that men with BPH may be at increased risk of prostate carcinoma due to these shared factors. METHODS: To elucidate this further, the authors used Swedish nationwide population-based record-linkage data to assess prostate carcinoma risk up to 26 years after the diagnosis of BPH among 86,626 men. RESULTS: Overall, relative to the general population, patients with BPH experienced little, if any, excess risk of prostate carcinoma (2% excess incidence after 10 years of follow-up). However, patients with BPH with and without surgical intervention experienced different prostate carcinoma risk patterns. Those undergoing transvesicular adenomectomy had a significant 22% lower incidence and a 23% lower mortality after the first 5 years of follow-up and those undergoing transurethral resection had a significant 10% higher incidence but a 17% lower mortality. In contrast, after the first 5 years, patients with BPH who did not receive surgical intervention experienced significant excesses of both prostate carcinoma incidence (18%) and mortality (77%). CONCLUSIONS: The differences in prostate carcinoma incidence and mortality by BPH treatment type suggest that factors related to treatment or health reasons underlying the selection of treatment influence subsequent prostate carcinoma risk. Further studies are needed to confirm the minimal excess risk of prostate carcinoma among BPH patients overall and the possible impact of BPH treatment methods on subsequent prostate carcinoma risk.

Aged↗
PubMed2004

FGF17 is an autocrine prostatic epithelial growth factor and is upregulated in benign prostatic hyperplasia.

BACKGROUND: Fibroblast growth factors (FGFs) are known to play an important role in the growth of prostatic epithelial cells. Benign prostatic hyperplasia (BPH) is characterized by increased epithelial and stromal proliferation within the transition zone of the prostate. FGF2, FGF7, and FGF9 are expressed in BPH tissue but expression of FGF17 has not been previously characterized in human prostate tissue. METHODS: Expression of FGF17 in human prostate tissue and primary cultures of prostatic epithelial and stromal cells was determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Growth response to FGF17 was assessed by addition of recombinant FGF17 to immortalized normal and neoplastic epithelial cell lines and primary cultures of prostatic stromal cells in the presence of insulin. Quantitative analysis of expression of FGF17 relative to keratin 18 and/or beta-actin in normal and hyperplastic prostate and prostate carcinoma was carried out by real-time quantitative RT-PCR. RESULTS: FGF17 is expressed by prostatic epithelial cells and can act as an autocrine growth factor for immortalized and neoplastic prostatic epithelial cells. It can also promote stromal proliferation, although only at higher concentrations. Expression of FGF17 per epithelial cell was increased 2-fold in BPH. CONCLUSIONS: FGF17 is expressed by normal, hyperplastic, and neoplastic prostatic epithelial cells and can promote epithelial proliferation in an autocrine manner. FGF17 expression is increased 2-fold in BPH and may contribute to the increased epithelial proliferation seen in this disease.

Cell Culture Techniques↗
PubMed2005

The potential impact of prostate volume in the planning of optimal number of cores in the systematic transperineal prostate biopsy.

OBJECTIVES: We compared the detection rates of different transperineal prostate biopsy protocols with the aim to optimize the number of cores to sample according to prostate volume. MATERIAL AND METHODS: From October 2002 to October 2004 we evaluated 480 consecutive patients with PSA between 2.5 and 20 ng/ml undergoing the first set of prostate biopsy. All patients underwent a 14-core TRUS-guided transperineal prostate biopsy, including 12 cores in the peripheral and two in the transitional zone. The detection rate of the 14-core scheme was compared to the one of the other biopsy schemes obtained through the exclusion of pairs of cores. Data were stratified according to the different TRUS estimated prostate volumes. RESULTS: The detection rate of the standard sextant was 35.2%, while those of the 8-core schemes ranged from 37.1 to 38.8%. The 10-core schemes yielded detection rates of 39.6-40.8% and the protocol with 12 biopsies in the peripheral zone diagnosed prostate cancer in 42.1% of the patients. In patients with <30 cc prostate volume, the detection rate of the 14-core scheme was 43.8% and resulted statistically overlapping to the 8-peripheral cores protocol. In patients with 30.1-50 cc prostate volume a 12-peripheral core biopsy reproduced the results of the 14-core sampling. In prostates larger than 50 cc, an even more extensive procedure was mandatory, considering the low detection rate of the 14-core scheme (24.2%). CONCLUSION: Transperineal prostate biopsy is a safe procedure with a very low complication rate and high cancer detection rate. Prostate volume is the most relevant variable in the planning of the optimal number of cores in the extensive first biopsy set. A protocol with more than 8 peripheral cores) is recommended only in patients with prostate volume larger than 30 cc.

Adult↗
PubMed2002

Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer.

PURPOSE: Gap junctions composed of connexin proteins have an essential role in intercellular communication and differentiation. Dysregulation of connexin expression is believed to have a role in carcinogenesis. The human prostate has been reported to express connexin 32 and 43. However, the expression pattern in prostate cancer is controversial, while to our knowledge connexin expression has not been reported in benign prostatic hyperplasia (BPH). To understand the potential involvement in prostate disease connexin 32 and 43 expression was evaluated in a series of normal prostate, BPH and prostate cancer specimens that were surgically removed due to bladder outlet obstruction. MATERIALS AND METHODS: Frozen sections of 23 normal, 43 BPH and 40 cancer involved prostates were evaluated for the presence, staining intensity and pattern of connexin 32 and 43 by immunocytochemical testing. RESULTS: In all specimens examined connexin 43 stain was punctate along the borders of the basal epithelial cells, whereas connexin 32 immunolocalized to luminal epithelial cells. In normal prostate connexin 43 and 32 were present in 87% and 65% of specimens, respectively, at low to moderate stain intensity. Importantly none of the normal samples were negative foreach connexin. In BPH specimens there was a marked increase in the incidence and intensity of connexin 43 and 32 immunostaining within epithelial cells. In addition, 23% of BPH samples showed strong connexin 43 expression in stromal cells. In contrast, connexin was decreased in prostate cancer specimens, of which 65% and 38% were negative for connexin 43 and 32, respectively, and 28% were negative for each type. In poorly differentiated tumors connexin 43 and 32 were present in only 10% and 40% of tumors, respectively, at low immunostaining intensity. CONCLUSIONS: In normal human prostate basal cells communicate via connexin 43 gap junctions, whereas luminal cells communicate via connexin 32 gap junctions. In BPH gap junctional intercellular communication is increased in epithelial and stromal cells, which may have a role in BPH pathogenesis. In prostate cancer gap junctional intercellular communication is decreased, is as indicated by decreased expression of connexin 43 and 32 with severe loss in poorly differentiated prostate cancer. These alterations in connexin expression may have a role in dedifferentiation and tumor progression.

Adenocarcinoma↗
PubMed2001

The molecular pathogenesis of prostate cancer: Implications for prostate cancer prevention.

Prostate cancer has become 1 of the most commonly diagnosed cancers in the United States and 1 of the leading causes of cancer death in North America and Western Europe. Survey studies of prostate tissues obtained at autopsy indicate that the development of life-threatening prostate cancer in the US likely occurs over decades. Insights from epidemiologic studies implicate environmental factors, principally dietary components, as major risk factors for prostate cancer development. An accumulating body of basic research data suggests that normal and neoplastic prostate cells may be subjected to a relentless barrage of genome-damaging stresses, and that dietary components and male sex steroids might modulate the level of genome threatening insults. Finally, over the past 5 years, analyses of somatic genome alterations in prostatic carcinoma cells have revealed that somatic inactivation of GSTP1, encoding the carcinogen-detoxification enzyme glutathione S-transferase pi, may serve as an initiating genome lesion for prostatic carcinogenesis. These diverse observations can be integrated into a transcendent mechanistic hypothesis for the pathogenesis of prostate cancer: normal prostate cells acquiring somatic GSTP1 defects may suffer chronic genome damage, influenced by dietary practices, that promote neoplastic transformation, while prostatic carcinoma cells, which characteristically contain defective GSTP1 alleles, remain susceptible to further genome-damaging stresses that promote malignant cancer progression. This hypothesized critical role for GSTP1 inactivation in the earliest steps of prostatic carcinogenesis provides several attractive opportunities for prostate cancer prevention strategies, including (1) restoration of GSTP1 function, (2) compensation for inadequate GSTP1 activity (via use of therapeutic inducers of other glutathione S-transferases (GST), and (3) abrogation or attenuation of genome-damaging stresses.

Atrophy↗
PubMed2003

Influence of prostate volume in the detection of prostate cancer.

OBJECTIVES: To assess the influence of prostate volume on prostate cancer (CaP) detection in men who underwent repeated sextant transrectal ultrasound biopsy of the prostate. METHODS: Between September 1991 and September 2000, 4376 men underwent sextant transrectal ultrasound-guided biopsy of the prostate. Of the 4376 men, 556 underwent repeat biopsy because of persistent prostate-specific antigen elevation (greater than 4 ng/mL) and/or an abnormal digital rectal examination or suspicious pathologic findings. The percentage of CaP missed on the initial biopsy and detected on the repeat biopsy between arbitrary prostate volumes of less than 50 and 50 cm3 or greater and between less than 37.5 and 37.5 cm3 or greater, the median prostate volumes of men with CaP, were compared. Patient age, prostate-specific antigen level, digital rectal examination findings, and Gleason score in each volumetric cutoff group were also compared. RESULTS: CaP was detected in 22% of men who underwent a repeat biopsy. The percentage of CaP missed on the initial biopsy but subsequently detected on the repeat biopsy consistently increased as the volume increased. A statistically significant difference in the percentage of CaP not detected on the initial biopsy was found between prostate volumes of less than 50 and 50 cm3 or greater and between less than 37.5 and 37.5 cm3 or greater (P <0.05). No statistically significant difference in prostate-specific antigen, age, digital rectal examination, or Gleason score was found between each volumetric cutoff group. CONCLUSIONS: A significant percentage of men are diagnosed with CaP after a repeat biopsy. We have demonstrated that the percentage of CaP missed on the initial biopsy and detected on the repeat biopsy increases as the prostate volume increases. The results of our study suggest that in men with large prostates, traditional sextant biopsies may not be adequate to detect CaP.

Age Factors↗
PubMed1999

Immunohistochemical finding of alpha-1-antichymotrypsin in tissues of benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Ratio of free to total (F/T) prostate-specific antigen (PSA) is higher in the blood of patients with benign prostatic hyperplasia than those with prostate cancer. To clarify the difference between ratios in these two, alpha-1-antichymotrypsin, the major component of the bound PSA in the blood, was immunohistochemically examined. METHODS: Tissues were obtained surgically via a retropubic approach from patients with benign prostatic hyperplasia (nine cases) and prostate cancer (27 cases). These samples were processed in paraffin blocks, cut into 5 mm sections and stained with antibodies against alpha-1-antichymotrypsin and PSA. RESULTS: The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer was higher than that in benign prostatic hyperplasia (P<0.05). Almost all of glandular and cancer cells were stained with PSA antibody. The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer did not correlate to histologic grade, although alpha-1-antichymotrypsin-stained cells were more widely scattered in high grade tissues. No correlation was found between alpha-1-antichymotrypsin-stained cells and ratio of F/T in the blood of cancer patients. In about 20% of cancer tissues, histiocytes with positive alpha-1-antichymotrypsin staining were found in stroma but not in that of benign prostatic hyperplasia. CONCLUSIONS: Prostate cancer tissues are shown to have a richer environment of alpha-1-antichymotrypsin than those of benign prostatic hyperplasia. Some cancer tissues contained alpha-1-antichymotrypsin-stained histiocytes. These local events may correlate to a high amount of the bound form among total PSA in the blood of prostate cancer patients.

Aged↗
PubMed2001

Prostatic fluid-free insulin-like growth factor-1 in relation to prostate cancer.

OBJECTIVES: To establish the feasibility of measuring free insulin-like growth factor-1 (IGF-1) in prostatic fluid and to determine if there is a difference in free IGF-1 levels in the prostatic fluid of patients with prostatic adenocarcinoma and in normal men. PATIENTS AND METHODS: Prostatic fluid samples were collected from men with histologically confirmed prostate cancer and from control subjects with no malignancy. Prostatic fluid and serum free IGF-1 levels were measured in duplicate by radioimmunoassay, and the differences analysed using the Mann-Whitney U-test and Pearson correlation. RESULTS: Prostatic fluid free IGF-1 concentrations did not differ significantly (P = 0.23) and there was no difference in serum free IGF-1 levels between the groups. While serum PSA level was significantly correlated with age (P < 0.001) the free IGF-1 level of prostatic fluid was not. There was also no correlation between prostatic fluid free IGF-1 and serum PSA levels. CONCLUSIONS: Free IGF-1 can be detected in prostatic fluid with acceptable sensitivity. However, the free IGF-1 level in prostatic fluid does not help to detect patients with prostate cancer and is not a tumour marker.

Adenocarcinoma↗
PubMed1998

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.

Animals↗
PubMed2003

Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml.

PURPOSE: In contemporary screening populations a major drawback of prostate specific antigen (PSA) is its relative lack of specificity, especially in the range of 4 to 10 ng/ml, where prostate cancer is found 25% of the time. ProPSA is a derivative of free PSA (fPSA) consisting of the truncated forms (eg [-2]proPSA, [-4]proPSA or the full-length [-7]proPSA). There is increasing evidence that proPSA is associated preferentially with prostate cancer. The objective of this study was to determine whether proPSA can influence the detection of early prostate cancer. MATERIALS AND METHODS: Archival serum samples obtained from 93 men who underwent a systematic 12-core prostate biopsy (total PSA range 4.0 to 10.0 ng/ml) were assayed for percent free PSA, total PSA and the 3 forms of proPSA (Hybritech Tandem Assays Beckman Coulter Access, Beckman Coulter, Inc., Brea, California). Free PSA, the cumulative sum of individual proPSA forms ([-2], [-4] and [-7], or sum-proPSA) and derivatives were determined. Of the 93 men assessed 41 (44%) had evidence of prostate cancer (76% Gleason 5/6, 19% Gleason 7 and 5% Gleason 8). Prostate volume was measured at systematic 12-core biopsy for the detection of prostate cancer. Results were analyzed using univariate and multivariate logistic regression (LR) nonparametric statistical methods. RESULTS: Using univariate LR, fPSA, percent fPSA (%fPSA), percent sum-proPSA and prostate volume significantly (p <0.05) differentiated men with prostate cancer from those with benign disease. However, applying stepwise backward multivariate LR, total PSA, %fPSA and sum-proPSA were retained and generated a receiver operator characteristic curve with an area under the curve of 76.6%. At 90% sensitivity these 3 variables collectively achieved a specificity of 44% for the detection of prostate cancer. Individually, the 3 retained variables had a specificity of 23% (total PSA), 33% (%fPSA) and 13% (sum-proPSA). CONCLUSIONS: Sum-proPSA, total PSA and %fPSA in combination improve the specificity of early prostate cancer detection in men with a total PSA of 4 to 10 ng/ml compared with the results of individual PSA molecular forms measured.

Adenocarcinoma↗
PubMed2005

Relationship between prostate specific antigen and indexes of prostate volume in Japanese men.

PURPOSE: We determined the relationship between serum prostate specific antigen (PSA) and indexes of prostate volume in Japanese men, and compared that relationship with the one in white men. MATERIALS AND METHODS: Data on a clinical cohort of 535 Japanese men with at least moderate lower urinary tract symptoms (LUTS) and clinical benign prostatic hyperplasia were examined. PSA, and total and transition zone prostate volume were related to age and linear regression analyses were performed to analyze the relationship between PSA and volume indexes. RESULTS: The group of 535 men with a median age of 68 years had a median serum PSA of 1.5 ng/ml, and a median total and transition zone volume of 26.8 and 8.8 ml, respectively. PSA, total prostate volume and transition zone volume increased almost linearly with age. On univariate regression with age with each successive decade total prostate volume increased by 10.65% (95% CI 5.4 to 16.2), transition zone volume increased by 20.84% (95% CI 11.84 to 30.56) and the transition zone index increased by 3.1% (95% CI 1.66 to 4.57). On multivariate analysis the PSA-total prostate volume relationship was statistically independent of age. The study suggests that Japanese men might produce or release more PSA per unit prostate volume than white men. CONCLUSIONS: Japanese men with LUTS and clinical benign prostatic hyperplasia but no evidence of prostate cancer might produce and/or release more PSA per unit prostate volume than white men. To our knowledge the cutoffs for PSA and prostate volume to predict the response to LUTS therapy and the development of complications in Japanese men are unknown. Future studies in Japanese men are needed to identify these cutoffs.

Adult↗
PubMed1988

Clinical behavior of prostatic specific antigen and prostatic acid phosphatase: a comparative study.

We assayed prostatic specific antigen and prostatic acid phosphatase serum levels in 1,383 patients using a double antibody radioimmunoassay (RIA) 125I. Establishing the upper normal limit in 10 ng/ml for prostatic specific antigen and 2.5 ng/ml for prostatic acid phosphatase, the false positive results were only 1.9 and 5.1% in men with nonprostatic benign or malignant pathology and 0 and 2.2% in women, respectively. We detected false positive levels in 3.5 and 4.7% of the patients with noncomplicated benign prostatic hypertrophy, 64.8 and 19.2% in complicated benign prostatic hypertrophy, 24 and 16% in acute prostatitis and 3.3% in chronic prostatitis for both tumoral markers. The sensibility in patients with prostate cancer was 87.2 and 64.1%, respectively, and there was better correlation with prostatic specific antigen than prostatic acid phosphatase levels on tumoral spread and histologic grading. Finally, the clinical efficacy was higher with prostatic specific antigen and it did not increase with the quantification of both tumoral markers.

Acid Phosphatase↗
PubMed1994

Prostate-specific antigen density: a means to enhance detection of prostate cancer.

The ability of serum prostate-specific antigen (PSA) and PSA density (PSAD) to distinguish patients with prostate cancer from those with benign diseases of the prostate was assessed in 495 men. All men were evaluated with PSA determination, digital rectal examination (DRE), transrectal ultrasonography (TRUS) and ultrasound-guided prostatic biopsies. PSA was analysed by the polyclonal (Yang) assay. Prostate volume was estimated from TRUS. PSAD was determined by dividing the serum PSA by the volume of the prostate. Prostatic biopsies identified cancer in 246 of the 495 patients (49.7%). The entire group was divided into 6 subgroups according to PSA level at presentation. Cancer and noncancer patients were compared in each subgroup with respect to the values of PSA, prostate volume and PSAD. For the entire group of patients, there was no statistically significant advantage, for PSAD over serum PSA alone, in distinguishing between benign and malignant prostatic conditions. However, when patients were stratified according to PSA level, PSAD was statistically significantly superior to serum PSA alone in the detection of prostate cancer for PSA values in the intermediate range (2.6-30 ng/ml). This analysis with respect to the DRE and TRUS results showed PSAD to be superior to PSA when both examinations are normal. Our results demonstrate that the influence of PSAD level on cancer detection proportionally increases as the PSAD value increases. Curves constructed from the incidence of prostate cancer according to PSAD values may be useful to select patients with intermediate levels of serum PSA, and normal DRE and TRUS for prostatic biopsies.

Adult↗
PubMed2006

Significance of noninvasive diagnosis of prostate cancer with cytologic examination of prostatic fluid.

OBJECTIVES: While reassessing the value of exfoliative cytologic examination of prostatic fluid (PF) for the diagnosis of prostate cancer, we found that PF is easily obtained with transrectal ultrasonography during prostate biopsy and that cytologic examination of PF is useful for the diagnosis of prostate cancer. METHODS: The cohort included 53 consecutive patients who underwent transrectal prostate biopsy from May through September 2005. Patient age was 66.7 +/- 7.24 years, and the mean concentration of prostate-specific antigen (PSA) was 15.1 +/- 25.8 ng/ml. The PF for cytologic examination was obtained before biopsy, and Papanicolaou's staining was performed. The results of cytologic examination are expressed as class 1 to 5. Results of cytologic examination and prostate tissue pathologic examination were analyzed. Patient age, PSA levels, total prostate volume (TPV), and PF volume were compared with cytologic class by means of analysis of variance. RESULTS: The mean PF volume was 378.4 +/- 245.3 microl, and the mean TPV was 38.0 +/- 18.8 ml. The numbers of patient in classes 1 to 5 were 1 (1.9%), 37 (69.8%), 11 (20.7%), 1 (1.9%), and 3 (5.7%), respectively. Pathologic examination showed 23 (43.4%) cases of cancer, 27 (50.9%) cases of benign prostatic hyperplasia, and 3 (5.7%) cases of high-grade prostatic intraepithelial neoplasia. All three patients with class 5 results had prostate cancer (Gleason score, 7 to 10). All 9 patients with a PSA level greater than 16 ng/ml had biopsy-proven cancer, and 3 of these 9 patients (33.3%) were in cytology class 5. Therefore, PF cytologic examination showed a specificity of 100% and a sensitivity of 33.3% in patients with PSA levels higher than 16 ng/ml. The cytologic classes differed in PSA levels (F=8.271, P=0.000) but not in patient age, TPV, or PF volume. CONCLUSIONS: Exfoliative cytologic examination of PF is a valuable, noninvasive method for detecting prostate cancer, especially in patients with high PSA levels.

Aged↗
PubMed2006

Conditional expression of human 15-lipoxygenase-1 in mouse prostate induces prostatic intraepithelial neoplasia: the FLiMP mouse model.

The incidence and mortality of prostate cancer (PCa) vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1), which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN), and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM) models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP)]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt), FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC), and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN) according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN). In summary, targeted overexpression of h15-LO-1 (a gene overexpressed in human PCa and HGPIN) to mouse prostate is sufficient to promote epithelial proliferation and mPIN development. These results support 15-LO-1 as having a role in prostate tumor initiation and as an early target for dietary or other prevention strategies. The FLiMP mouse model should also be useful in crosses with other GEM models to further define the combinations of molecular alterations necessary for PCa progression.

Animals↗
PubMed2000

Antibody immunity to prostate cancer associated antigens can be detected in the serum of patients with prostate cancer.

PURPOSE: Several immune based therapies targeting prostate cancer associated proteins are currently undergoing clinical investigation. In general, however, little is known about the immunogenicity of prostate cancer or which prostate cancer associated proteins elicit immune responses. We determine whether patients with prostate cancer have antibody immunity to known prostate cancer associated proteins, what the prevalence of this immunity is and whether immunity to individual proteins is associated with the stage of disease. MATERIALS AND METHODS: We evaluated the inherent humoral immune response against prostate specific antigen (PSA), prostatic acid phosphatase, p53 and HER-2/neu, all known prostate cancer associated proteins, in 200 patients with various stages of disease and male controls. RESULTS: Antibody immunity to PSA was significantly different between the patient (11%, 22 of 200) and control populations (1.5%, 3 of 100, p = 0.02), and titers 1:100 or greater were particularly prevalent in the subgroup of patients with androgen independent disease (11%, 6 of 56). Antibody immunity to prostatic acid phosphatase and p53 was detected (5.5%, 11 of 200 and 6%, 12 of 200), and was not different from the control population (4%, 4 of 100, p = 0.57 and 7%, 7 of 100, p = 0.74). Antibody immunity to HER-2/neu was significantly higher in patients with prostate cancer (15.5%, 31 of 200) compared to controls (2%, 2 of 100, p = 0.0004), and titers 1:100 or greater were most prevalent in the subgroup of patients with androgen independent disease (16%, 9 of 56). CONCLUSIONS: These findings suggest that prostate cancer is an immunogenic tumor. Moreover, for PSA and HER-2/neu the prevalence of antibody immunity was higher in patients with androgen independent disease, indicating that even patients with advanced stage prostate cancer can have an immune response to their tumor.

Acid Phosphatase↗
PubMed2001

The usefulness of prostate specific antigen density as a screening method for prostatic carcinoma.

Prostate specific antigen (PSA) has been used extensively for monitoring the progression of prostatic cancer since its discovery in 1979. Unfortunately the measurement of PSA in serum is not sufficiently specific for early detection of prostatic carcinoma (CaP) as it is secreted by normal as well as hyperplastic or cancerous prostatic tissue. As serum PSA is the reflection of the number of prostatic epithelial cells, a small cancerous prostate gland having increased number of cells per unit volume leaks more PSA in serum than a benign, large gland. Thus the concept of PSA density (PSAD) has been proposed (the quotient of serum PSA divided by the volume of prostate in cubic centimeter) as an indicator for prostatic malignancy. In the present study pre-operative PSAD values of 65 cases of prostatic diseases were calculated [54 cases of benign prostatic hyperplasia (BPH) and 11 cases of C3P]. Serum PSA was measured by enzyme linked immunosorbent assay (ELISA) method and the prostatic volume was measured by transrectal ultrasonography (TRUS). Although 8 cases of BPH (14.8%) had raised PSA level, abnormal PSAD (0.1 or above) was noted in only 3 cases. All cases having PSAD value above 0.2 had carcinoma. The PSAD value above 0.1 in cases of CaP was found to be significant (p<0.001). By using PSAD as screening test the sensitivity increased from 85.1% to 94.4% and positive predictive value increased from 55.5% to 75%, compared to the detection of carcinoma by measuring PSA alone. The present study concludes that PSAD is more useful for prediction of CaP and the need of prostatic biopsy for early detection.

Aged↗