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PubMed1999

Influence of high-grade prostatic intra-epithelial neoplasia on total and percentage free serum prostatic specific antigen.

OBJECTIVE: To analyse the influence of high-grade prostatic intra-epithelial neoplasia (HGPIN) on total and percentage free serum prostatic specific antigen (PSA). PATIENTS AND METHODS: The total and free serum PSA levels were measured (using a double-monoclonal antibody immunoassay, Tandem and Tandem free PSA, Hybritech Inc, Liège, Belgium) in 570 consecutive patients undergoing sextant ultrasound-guided prostatic biopsy because of an abnormal digital rectal examination or a serum PSA concentration of > 4.0 ng/mL. The main diagnosis was benign disease in 321 (56%) and prostate cancer in 249 (44%). HGPIN was detected in 85 (15%) of the patients; in 17 (20%) it was associated with benign tissue and in 68 (80%) with prostate cancer. RESULTS: Patients with benign disease had a median total serum PSA level of 7.2 with no HGPIN and 7.7 ng/mL when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 16.0 and 15.9 ng/mL (P>0.05). The median percentage free serum PSA was 15.8 in patients with HGPIN-free benign disease and 14.1 when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 9.7 and 11.0 (P>0.05). In a multivariate analysis, prostate cancer was the major contributor to total and percentage free serum PSA levels. CONCLUSION: The presence of HGPIN does not contribute significantly to total and percentage free serum PSA levels.

Adult↗
PubMed1987

Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate.

To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.

Acid Phosphatase↗
PubMed1988

Prostate-specific antigen in prostatic cancer.

In an attempt to establish the value of prostate-specific antigen (PSA) in prostatic cancer, serum PSA measurements were performed in 600 patients, including 75 previously untreated prostatic cancer patients. The mean PSA levels in the benign prostatic hypertrophy (BPH) and cancer groups were highly significantly different, but less difference was found between BPH and localized prostatic cancer. A PSA level above 50 ng/ml was never recorded for BPH, but lower levels can be due to either prostatic cancer or to BPH. Our data suggest that PSA is not a specific marker of prostatic cancer but increased serum PSA levels must draw the physician's attention to the possible presence of prostatic cancer.

Antigens, Neoplasm↗
PubMed1995

Correlation between serum prostate specific antigen levels and the volume of the individual glandular zones of the human prostate.

To analyze the correlation between serum prostate specific antigen (PSA) levels and the volume of the individual glandular zones of the human prostate, we examined 31 cystoprostatectomy specimens as well as 13 radical prostatectomy specimens with a prostate cancer volume of 0.3 cc or less, no bladder cancer infiltrating the prostate, no granulomas or severe inflammation, as well as no patient history of radiation, transurethral resection of the prostate or hormonal treatment. The volumes of the peripheral zone, transition zone and central zone were separately determined by outlining the zonal boundaries during microscopic examination of all slides at each level of section. PSA was measured by the Yang polyclonal assay. In the univariant regression analysis the correlation coefficients among serum PSA and transition zone, peripheral zone and central zone volumes were 0.934, 0.546 and 0.368, respectively, strongly suggesting that most PSA leakage from the prostate into the serum comes from the transition zone. The regression of serum PSA and transition zone volumes leads to a prediction of approximately 0.261 ng./ml. PSA per gm. benign prostatic hyperplasia (BPH) plus an intercept of 0.878, a number in keeping with our 1987 estimates of 0.3 ng./ml./gm. BPH. The volumes of the 3 zones appeared to be independent variables. Transition zone volume showed the greatest variation because of BPH. The mean average ratio of peripheral zone volume to central zone volume was nearly 3:1. These data strongly support the concept of age-adjusted PSA levels, since most of the increase in size of the prostate with increasing patient age comes from the transition zone from which BPH develops.

Adult↗
PubMed2005

C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer.

OBJECTIVE: To further analyse the relationship of c-reactive protein (CRP) levels to prostate cancer, by measuring CRP in men with prostate cancer and benign prostatic hypertrophy (BPH), as chronic inflammation has long been linked to cancers with an infectious cause and CRP is a nonspecific marker for inflammation, associated with prostate cancer incidence and progression. PATIENTS AND METHODS: Data from 114 men, most of whom had had radioactive seeds implanted, were evaluated from November 1990 to April 2002. In addition, 27 men were included who had biopsy-confirmed BPH. CRP was assessed with an automated chemiluminometric high-sensitivity assay kit. RESULTS: There was no significant difference in CRP levels in men with localized prostate cancer or BPH but levels were significantly higher in men with bone metastases. There was also a significant correlation of CRP level with prostate-specific antigen (PSA) in those with cancer. Because PSA is correlated with disease stage, multiple linear regression was used with CRP as the dependent variable, and PSA and disease stage as independent variables. The regression was significant overall (P < 0.001) and the effect of disease stage on CRP (P < 0.001) was independent of the effect of PSA level (P = 0.001). CONCLUSION: The strong association of CRP with PSA, independent of tumour stage, suggests that inflammation might be fundamental in prostate cancer, and that chronic inflammation may be a legitimate target for prostate cancer chemoprevention and treatment.

Aged↗
PubMed2000

Determination of the percentage of free prostate-specific antigen helps to avoid unnecessary biopsies in men with normal rectal examinations and total prostate-specific antigen of 4-10 ng/ml.

OBJECTIVE: To assess the usefulness of measuring the percentage of free prostate-specific antigen (PSA) in serum to reduce the number of prostate biopsies in men with serum PSA levels between 4 and 10 ng/ml and benign prostate examinations. MATERIALS AND METHODS: The percentage of free PSA (Immulite((R))) in serum was analyzed prospectively in 180 men with benign digital rectal examinations and total PSA serum levels of between 4 and 10 ng/ml. All patients underwent ultrasound-guided sextant prostatic biopsies. Sensitivity, specificity and positive and negative predictive values were calculated as well as the percent of patients in which biopsies could have been avoided for various cutoff values of the percentage of free PSA as an indicator for biopsy. Influence of age in the determination of cut points was evaluated. RESULTS: Cancer was detected in 22.2% (40/180) of the patients. Mean percentage of free PSA was 13.4% in patients with cancer and 18.9% in patients with benign prostatic hyperplasia (p = 0.001). Using a percentage of free PSA cutoff of 22% or less as a criterion for performing prostatic biopsy would have detected 95% of cancers, avoided 25% of benign biopsies and yielded a positive predictive value of 29% in patients who underwent biopsy. Mean percent of free PSA values increased as mean subject age increased, influencing the calculation of cut points, sensitivity and specificity. Leaving the cut point constant across all age groups will oblige older patients to undergo an increased number of unnecessary biopsies, although allowing for higher sensitivity in younger men. CONCLUSIONS: Measurement of the percentage of free serum PSA improves specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations. Subject age seemed to influence the determination of optimal cut points.

Aged↗
PubMed2006

Study of prostatic fluid from patients with elevated levels of prostate-specific antigen.

INTRODUCTION: Characteristics of prostatic fluid (PF), which can be obtained in large amounts during screening transrectal ultrasound just before prostate biopsy to detect prostate cancer, were investigated. These characteristics include the amount of PF obtained and the number of leukocytes in PF, which would be useful for planning cell-biological or immunological studies of leukocytes in PF and for increasing the understanding of prostatitis in elderly men. PATIENTS AND METHODS: The volume of PF and the number of leukocytes in PF were measured in 50 patients suspected of having prostate cancer because of elevated levels of serum prostate-specific antigen (PSA). Correlations of the volume of PF, the number of leukocytes per milliliter, the total leukocyte number with age and prostate volume and correlation of PSA levels with the number of leukocytes per milliliter and total leukocyte number were also investigated. RESULTS: The average patient age was 67.2 years, and PF specimens were obtained from 43 of the 50 patients (86%). The mean +/- SD of PF volume, number of leukocytes in PF, and total leukocyte number were 347.65 +/- 305.76 microl, 4.84 +/- 6.07 x 10(6) /ml, and 1.47 +/- 2.10 x 10(6), respectively. A correlation was observed only between the total leukocyte number and the volume of the transitional zone (P=0.039). CONCLUSIONS: These data provide information for investigators to plan cell-biological or immunological studies of leukocytes in PF and for understanding prostatitis in elderly men.

Aged↗
PubMed2006

Analysis of the risk factors for incidental carcinoma of the prostate in patients with benign prostatic hyperplasia.

PURPOSE: To determine the occurrence of incidental carcinoma of the prostate, its characteristics, and the risk factors for this diagnosis in a group of patients surgically treated for benign prostatic hyperplasia. METHODS: The study comprised a retrospective analysis of 218 patients. After surgical treatment, patients with the finding of incidental carcinoma of the prostate were compared to those without this finding. The preoperative variables analyzed were patient age, digital rectal examination, PSA, PSA density, prostate volume, and preoperative prostate biopsy. We also determined the sensitivity, specificity, positive predictive value, and negative predictive value of digital rectal examination and PSA for the finding of incidental carcinoma of the prostate at surgical specimen analysis. RESULTS: Thirteen (6.2%) out of the 218 patients presented incidental carcinoma of the prostate. Eight (61.5%) of these tumors were classified as T1a and 5 (38.5%) as T1b. Only advanced age (P = 0.003) and the presence of a suspect digital rectal examination (P = 0. 016) were statistically related to the findings of the surgical specimen analysis. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of incidental carcinoma were 23.0%, 96.6%, 30.0%, and 95.2% for a suspect digital rectal examination and 85.0%, 34.1%, 7.5%, and 97.2% for a PSA greater than 4.0 ng/mL. The accuracy for these methods was 92.2% and 37.1%, respectively. CONCLUSIONS: Advanced age and the presence of a suspect digital rectal examination represent the most important risk factors for the diagnosis of an incidental carcinoma of the prostate. However, the low positive predictive values reflect the weak correlations among these variables.

Age Factors↗
PubMed2004

[Prostate cancer after prostatectomy for benign prostatic hyperplasia].

OBJECTIVE: To study the diagnosis and treatment of prostate cancer after prostatectomy for benign prostatic hyperplasia (BPH). METHODS: Twelve cases of prostate cancer after prostatectomy for benign prostatic hyperplasia were reviewed and studied. The mean intervals between prostatectomy for BPH and the diagnosis of prostate cancer was 10 months to 14 years, 5.6 years on average. The main symptoms were dysuria, hematuria and pain. Serum prostate specific antigen (PSA) was elevated in 11 cases. Digital rectal examination (DRE) was abnormal in 8 cases. Three cases were in clinical stage B, 3 in stage C and 6 in stage D. Ten cases received combined androgen blockade therapy. Monotherapy with surgical castration was given to 2 cases. Three patients with urinary tract obstruction received additional treatment of TURP. RESULTS: During the 4 months to 8 years follow-up, 3 patients died, 6 remained stable and 2 deteriorated. CONCLUSION: Surgery for BPH could not prevent the development of prostate cancer. PSA and DRE were the main methods for the diagnosis of this prostate cancer.

Aged↗
PubMed1991

[Clinical and pathological study of tumor marker in benign prostatic hypertrophy and incidental prostatic cancer].

To determine the value of prostatic markers for prostate cancer, serum prostatic acid phosphatase (PAP), prostate specific antigen (PSA) and gamma-Seminoprotein (gamma-Sm) were measured in 81 patients with benign prostatic hypertrophy and in 12 patients with incidental prostatic cancer. gamma-Sm was the most sensitive but the least specific of the three markers. Large prostate glands, especially hyper-glandular type tended to be associated with high gamma-Sm levels in our study. Patients with acute urinary retention, acute prostatitis and necrosis also showed positive markers. Out of 12 patients with incidental cancer, 5 patients had more than 2 elevated markers. Four patients with poorly differentiated adenocarcinoma failed to show increased markers.

Acid Phosphatase↗
PubMed1998

Prostate-thyroid axis: stimulatory effects of ventral prostate secretions on thyroid function.

BACKGROUND: Endocrine cells of the prostate secrete thyrotropin (TSH)-releasing hormone (TRH), TRH- and TSH-like peptides, and growth factors. Propylthiouracil- and methimazole-induced hypothyroidism increased prostatic levels of TRH in rats as in hypothalamus, whereas thyroxine (T4) replacement decreased TRH. From these reports, we inferred the existence of a prostate-thyroid axis. METHODS: The influence of the prostate on the thyroid gland was studied in albino rats. Ventral prostate was surgically removed on day 31 postpartum. The animals were sacrificed on day 60 postoperation. Serum thyroid hormones were assayed by radioimmunoassay (RIA). For in vitro studies, normal thyroid and ventral prostate glands were cocultured with or without thyroid-stimulating hormone (TSH) antibody, to assess the direct influence of prostatic secretions on thyroid hormone secretion. RESULTS: Serum total and free T4 and triiodothyronine (T3) were significantly reduced in ventral prostatectomized rats. Histological analysis of the thyroid showed that the diameters of the peripheral and middle follicles, colloid epithelial cells, and nuclei were increased in prostatectomized rats, indicating hypothyroid status. Total T3 and T4 were significantly elevated in the culture medium when thyroid and prostate were cocultured, irrespective of the presence of TSH antibody. CONCLUSIONS: The present study suggests that ventral prostatic secretions have a stimulatory role on the thyroid gland.

Aging↗
PubMed2000

Prostatic luminal cell differentiation and prostatic steroid-binding protein (PBP) gene expression are differentially affected by neonatal castration.

BACKGROUND: Although normal prostatic development is androgen-dependent, the prostate continues to grow in the neonate despite castration. However, the manner in which neonatal growth of the prostate occurs, in the absence of the testis, remains largely unknown. The purpose of this study was to examine the differentiation of prostatic epithelial cells after neonatal castration. METHODS: Immunohistochemistry was utilized to detect the expression of differentiation products: basal-cell cytokeratin (CK 5), luminal-cell cytokeratin (CK 18), and prostatic steroid-binding protein (PBP), a ventral prostate-specific marker indicative of secretory function in luminal cells. The reverse transcription-polymerase chain reaction was used to detect transcription products of the three polypeptide subunits of PBP, designated C1, C2, and C3. Rats were castrated on day 5 after birth, and ventral prostates were collected on day 14. Dihydrotestosterone was injected (100 microg/animal every 2 days) in castrated animals to determine if PBP expression could be initiated by androgen. RESULTS: Although no major effects of castration were detected on the differentiation of stromal or basal cells (which differentiate prior to day 5), castration had a pronounced effect on luminal-cell differentiation. Castration inhibited PBP protein expression, but did not affect the expression of luminal-cell cytokeratin (CK 18) protein. Furthermore, castration reduced C1, C2, and C3 transcription. Androgen replacement to castrated animals allowed for the initiation of PBP expression, although its onset was delayed. CONCLUSIONS: These observations indicate that the testis is not necessary for prostatic luminal-cell differentiation, but is necessary for full expression of luminal-cell secretory phenotype. Furthermore, our study suggests that factors of testicular origin, in addition to androgen, are needed for proper timing of PBP expression. This investigation establishes that the cytological and the physiological differentiation of the rat prostate are differentially regulated.

Androgen-Binding Protein↗
PubMed2001

Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells.

BACKGROUND: The neuroendocrine cells of the human prostate have been related to proliferative disorders such as prostatic cancer. Their origin, distribution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. METHODS: Prostatic tissue specimens (n = 20) from human fetuses (n = 8), prepubertal and pubertal children (n = 8) and mature men (n = 4) were studied immunohistochemically using antibodies directed against neuroendocrine, epithelial as well as secretory markers. Semiquantitative computer-assisted evaluation of different epithelial and stromal components based on stereological principles was performed on azan-stained sections representative of all developmental stages. RESULTS: By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely associated with the formation of urethral prostatic buds. The fetal and postnatal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular peripheral acini. In peripheral ducts, the distribution is random. Maturation of the NE cells precedes that of the secretory cells by about 10-16 years. CONCLUSIONS: A second prostatic stem cell lineage, different from the urogenital sinus (UGS)-lineage is hypothesized originating from immature neuroendocrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. Their presence is apparently important for proliferation regulation of the UGS-derived lineage of the prostate.

Adolescent↗
PubMed2005

Combined c-Myc and caveolin-1 expression in human prostate carcinoma predicts prostate carcinoma progression.

BACKGROUND: Over-expression of the oncogene c-Myc has been implicated in the development and progression of human prostate carcinoma. However, previous assessments of c-Myc expression have not revealed its potential for predicting prostate carcinoma progression. Caveolin-1 is associated with prostate carcinoma progression and is a downstream target gene of c-Myc. The observation that caveolin-1 can suppress c-Myc-induced apoptosis suggested the potential for cooperation between c-Myc and caveolin-1 in malignant progression. In this study, the authors evaluated the prognostic potential of combined c-Myc and caveolin-1 expression in human prostate carcinoma progression. METHODS: Immunostaining with c-Myc and caveolin-1-specific antibodies was performed on paraffin sections from 104 radical prostatectomy specimens from men with lymph node negative prostate carcinoma. Combined c-Myc and caveolin-1 immunostaining scores were related with the clinical and pathologic features and the probability of prostate-specific antigen recurrence after surgery. RESULTS: The combination of c-Myc and caveolin-1 immunopositivity correlated positively with Gleason score (rho = 0.219; P = 0.0253) and positive surgical margin (rho = 0.333; P = 0.0006). The combination of positive c-Myc and caveolin-1 in patients with clinically confined prostate carcinoma was a significant prognostic marker for the time to disease progression after surgery in both univariate analysis (P = 0.0039; hazard ratio, 3.035) and multivariate analysis (P = 0.0114; hazard ratio, 2.916). CONCLUSIONS: The coexpression of c-Myc and caveolin-1 showed potential as a useful prognostic marker for human prostate carcinoma. The current results suggest interactions between c-Myc and caveolin-1 in the progression of human prostate carcinoma.

Adenocarcinoma↗
PubMed1992

The inhibition of the paracrine progression of prostate cancer as an approach to early therapy of prostatic carcinoma.

The prevalence of neural elements in prostatic carcinoma and their effects on the behavior of the lesion have recently been recognized. Recent reports suggest that chromogranin-A- and neuron-specific enolase-expressing tumors have an earlier progression and a lower response rate to hormonal therapy. The extreme presentation of this tumor is presumed to be small cell carcinoma of the prostate. This bombesin-secreting tumor, which has a characteristic clinical picture of early visceral involvement, wide-ranging metastases, and a relatively low rate of expression of PSA and PAP, is highly responsive to chemotherapy. The relatively high rate of expression of neural elements in primary prostatic carcinoma is discordant with the low frequency of clinical small cell carcinoma of the prostate. In order to account for these differences, one can assume that neural elements may play a role in the progression of this disease by either developing their own neoplastic process (small cell carcinoma of the prostate) or, in the majority of cases, causing paracrine progression of the tumor. Bombesin is typically secreted by small cell carcinoma of the lung and possibly by the prostate. It has been shown to be a growth factor mediating the progression of this disease in a number of experiments. Preclinical data demonstrate increased invasiveness and increased proliferation associated with bombesin in the treatment of prostatic carcinoma. Based on the hypothesis that neural peptides may be important mediators of androgen-independent growth of prostatic carcinoma as well as predicting poor prognosis, inhibition of these factors may represent a therapeutic strategy of relevance for the treatment of patients with prostatic carcinoma.

Animals↗
PubMed2001

Differential expression of c-erb B2/neu, epidermal growth factor receptor, cytokeratin 8, and the prostatic steroid-binding protein gene in rat ventral prostate during postnatal development.

BACKGROUND: The development and progression of prostate neoplasia may recapitulate the early developmental pattern of expression of genes in the prostate. The study of prostate development may, therefore, provide insights into the molecular mechanisms important in prostate neoplasia and reveal new markers. METHODS: We compared postnatal expression of four genes: neu and epidermal growth factor receptor genes (EGFR), androgen-upregulated in the ventral prostate of adult rats (C-3), and androgen-repressed (CK8) in Sprague-Dawley rats. In situ hybridization was performed on prostate frozen sections collected on postnatal days 1, 5, 10, 15, 20, 30, and 60 from five rats per day. Staining intensities for antisense probes specific for each gene were determined relative to day 1 intensity. RESULTS: Growth factor receptors including neu and EGFR may be coordinately regulated in the basal-cell population during prostate development. CK8 and C-3 show evidence of similar androgen regulation during development. CONCLUSIONS: CK8 and C-3 have distinct patterns of expression in the postnatal period of development and these genes may be good markers of differentiation. Both neu and EGFR may be involved in androgen-independent growth of basal cell population in prostate. Prostate 47:164-171, 2001.

Androgen-Binding Protein↗
PubMed2001

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.

BACKGROUND: To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. METHODS: Consecutive sections from 43 prostates taken during autopsy representing fetuses (12-38 weeks of gestation), infants, prepubertal males and adults were double stained for chromogranin A and MIB-1. MIB-1 labeling index (LI) was calculated in the budding tips, forming acini, major collecting ducts, adjacent and non-adjacent stromal compartments. Furthermore, the topographic relationship between proliferating cells and NE cells was evaluated. RESULTS: In the first half of gestation, cell proliferation as revealed by MIB-1 LI was significantly higher in epithelial structures and stroma than in older fetuses and other age groups. MIB-1 LI was higher in budding tips than in other epithelial regions. MIB-1 LI in stroma adjacent to budding tips was not higher than that adjacent to other epithelial branching segments. Co-expression of chromogranin A and MIB-1 staining was not observed. MIB-1 LI was lower in cells in the direct vicinity of chromogranin A positive NE cells than at a distance from NE cells. CONCLUSIONS: Prostate development in the first half of gestation is explosive. Thereafter, the prostate basically is a slow-growing organ. Budding tips are the major growth foci during early prostate development, while stromal growth is evenly distributed throughout the prostate, probably indicating that stromal-epithelial interactions do not manifest in enhanced proliferation at their interface. NE cells may have an inhibitory effect on proliferation of exocrine epithelial cells and are probably only associated with differentiation of prostate exocrine cells in the prostate.

Adult↗
PubMed2005

Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis.

BACKGROUND: Cancer patients produce autoantibodies to self-proteins called tumor-associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS: Serum autoantibodies to the survival protein lens epithelium-derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting. RESULTS: Anti-LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P < 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells. CONCLUSIONS: The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients.

Adenocarcinoma↗