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PubMed1999

Elevated serum prostate specific antigen levels in conjunction with an initial prostatic biopsy negative for carcinoma: who should undergo a repeat biopsy?

OBJECTIVE: To determine the outcome of repeated prostatic biopsies in men attending with suspected prostate cancer but an initial negative biopsy. PATIENTS AND METHODS: Patients who had undergone two or more transrectal ultrasonography (TRUS)-guided prostate biopsies were identified from the Hospital Information Support System database. Indications for TRUS were a raised prostate-specific antigen (PSA) level (>4.0 ng/mL), with or without an abnormal digital rectal examination (DRE). Sextant prostate biopsies plus biopsies of any suspicious hypoechoic area or area of DRE abnormality were obtained for histology. Forty-eight patients underwent repeat TRUS-guided prostatic biopsies (mean age 67.5, sd 7. 25, range 53-82 years). RESULTS: The mean (sd, median, range) PSA level was 16.9 (13.5, 11.6, 5.2-61.8) ng/mL. Fifteen patients (31%) had carcinoma on repeat biopsy, 11 after the second and four after a third biopsy. The positive repeat biopsy rate was 24% where the PSA level was 4.0-9.9 ng/mL, 33% if the level was 10.0-19.9 ng/mL and 39% if it was >/=20.0 ng/mL. There was no significant difference in age or initial PSA concentration between those men with positive and those with negative repeat biopsies. However, patients with cancer had significantly higher PSA levels before repeat biopsy than at first biopsy (P=0.0043) and had greater PSA velocities than had patients with no diagnosis of cancer (P=0.0067). CONCLUSION: Where sufficient clinical suspicion exists, despite an initial negative biopsy, repeat TRUS-guided prostate biopsies should be carried out to exclude carcinoma of the prostate.

Aged↗
PubMed1998

Prostate-specific antigen (PSA), PSA density and age-adjusted PSA reference values in screening for prostate cancer--a study of a randomly selected population of 2,400 men.

Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400 randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with prostate cancer were diagnosed. The PSA results were correlated to the diagnosis, the men's age, and the prostate volume. Least square regression analysis was used to calculate the 95% upper confidence intervals for PSA in each year of age in men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii) PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A significant correlation was found between PSA and prostate volume, between PSA and age, and between the prostate volume and age. The calculated annual growth of the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted upper PSA reference values for the three age categories studied (55-59, 60-64 and 65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4 ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were 17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies.

Age Factors↗
PubMed1995

Prostate bed massage as a means to determine the source of a rising prostate specific antigen after radical prostatectomy.

PURPOSE: To determine the value of prostate bed massage as a means to determine whether a rising prostate specific antigen (PSA) after radical prostatectomy is due to local recurrence or distant metastases. METHODS AND MATERIALS: Eighteen patients referred for pelvic radiotherapy because of a rising PSA after radical prostatectomy had PSA levels measured immediately before and 5 minutes after a vigorous 30-second massage of the prostate bed. RESULTS: Only one of the 18 (5%) patients experienced a rise in their PSA following vigorous prostate bed massage. Fifteen of the 18 (83%) patients' PSA levels declined after radiotherapy, suggesting that recurrent prostate cancer had been present in the prostate bed at the time of prostate massage in these patients. Only 1 of these 15 patients (7%) had a rise in their PSA after massage. CONCLUSION: Prostate bed massage, as performed in this study, was not helpful to determine whether a rise in PSA after radical prostatectomy was due to local or distant recurrence.

Humans↗
PubMed2002

Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma: a detailed analysis of radical prostatectomy specimens from a randomized trial.

Neoadjuvant hormonal therapy (NHT; androgen ablation) is used prior to radical prostatectomy (RP) in an attempt to pathologically "downstage" prostatic adenocarcinoma and ultimately to improve disease-free survival. This study describes the pathologic effects of NHT with the antiandrogen cyproterone acetate, 300 mg/day for 12 weeks, on the RP specimens from men with clinically localized (stage T1 or T2) prostatic adenocarcinoma. There were 101 men in the pretreatment group (CPA) and 91 men in a control group who were treated with surgery alone. The prevalence and extent of morphologic effects were recorded for the nonneoplastic prostate, high-grade prostatic intraepithelial neoplasia, and invasive adenocarcinoma. The commonest effects on the nonneoplastic prostate were atrophy and basal cell hyperplasia and prominence. High-grade prostatic intraepithelial neoplasia was more commonly identified in the surgery alone group than the CPA group (p <0.01). In the CPA group, flat and low tufted patterns of high-grade prostatic intraepithelial neoplasia predominated. Following NHT, the adenocarcinoma showed characteristic morphologic alterations, including reduction in cytoplasmic quantity, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, and mucinous breakdown. In many cases there was prominence of collagenous stroma, obscuring malignant glands. Compared with the surgery alone group, the CPA group RP specimens had a significantly lower mean specimen weight (40.3 g vs 46.5 g, p = 0.025) and less tumor extent by several measures. Organ-confined tumor (stage pT2, margin negative) was found in 41.6% of the CPA group compared with 19.8% of the surgery alone group (p = 0.0017). The overall rate of margin positivity was lower in the CPA group (27.7% vs 64.8%, p = 0.001). We consider that the difference in margin positivity is the result of tumor shrinkage with a decreased likelihood of sampling in routine sections. There was no significant difference in the rate of extraprostatic extension between the two groups. There was elevation of the Gleason score in the RP specimens versus baseline biopsy in 60% of the CPA group compared with 33% of the surgery alone group (p = 0.02). The higher rate of elevation in the CPA group largely resulted from an increase in primary or secondary Gleason score 5 tumor, a morphologic artifact introduced by NHT. Because of this, we recommend not giving a Gleason grade to RP specimens following NHT. Monotherapy with CPA has similar pathologic effects on benign and malignant prostate tissue as does dual agent androgen blockade. Prolonged follow-up of these patients is required to determine if NHT with CPA leads to improved disease-free survival.

Adenocarcinoma↗
PubMed1995

Differential expression of apolipoprotein-D and prostate specific antigen in benign and malignant prostate tissues.

PURPOSE: To investigate Apolipoprotein-D (Apo-D) and prostate specific antigen (PSA) immunohistochemical staining of nonmalignant and malignant human prostate tissues. MATERIALS AND METHODS: Apolipoprotein-D and PSA immunoreactivity were evaluated by video image analysis in nonmalignant prostates and in 30 stage D2 prostate cancers. RESULTS: Apolipoprotein-D was detected in all 30 tumors, and the level of staining was elevated in comparison to age-matched nonmalignant prostates (p < 0.05). In contrast, the level of PSA staining in tumors was less than that detected in nonmalignant prostates. CONCLUSIONS: Apolipoprotein-D is expressed in normal human prostate. Elevated Apo-D staining is associated with advanced prostate cancer.

Adolescent↗
PubMed2000

Prostate specific antigen and benign prostatic hyperplasia.

Benign prostatic hyperplasia is a common condition in males over 50 years, but prostate cancer can develop in the same population. Prostate specific antigen, the best marker for prostate cancer, is also produced by benign epithelial cells, and there is an overlapping phenomenon between both conditions. The better we understand the relationships between benign prostatic hyperplasia and prostate specific antigen, the higher will be the discrimination power of prostate specific antigen measurement as a marker for prostate cancer. Our scope includes a review of the latest published material to date on this subject.

Age Factors↗
PubMed2003

5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium.

PURPOSE: In the prostate testosterone is converted to the more potent androgen dihydrotestosterone by the enzymes 5alpha-reductase (5alphaR) types 1 (5alphaR1) and 2 (5alphaR2). Since 5alphaR2 is the dominant prostatic enzyme, the 5alphaR2 selective inhibitor finasteride has been widely used to treat benign prostatic hyperplasia (BPH). However, inhibition of both 5alphaR enzymes provides a greater decrease in serum dihydrotestosterone. We developed a specific antibody to 5alphaR1 and assessed expression in BPH and prostate cancer (pCa) tissue. The presence of this isoenzyme in localized prostate cancer would provide a rationale for assessing the efficacy of dual inhibition for prostate cancer prevention. MATERIALS AND METHODS: A polyclonal antibody to 5alphaR1 was developed and validated using 5alphaR1 and 5alphaR2 transfected COS-1 cells. A total of 26 BPH and 53 pCa specimens were assessed for 5alphaR1 protein expression using immunocytochemical methods. Also, 29 BPH and 37 pCa specimens were assayed for 5alphaR1 and 5alphaR2 enzyme activity. RESULTS: Specificity of the 5alphaR1 antibody was confirmed using transfected COS-1 cells. Cells transfected with 5alphaR1 showed specific staining in immunocytochemistry experiments and on Western blotting of cell lysates the expected 24 kDa band was observed. High intensity immunoreactivity for 5alphaR1 was observed in the tumor epithelium of 28% of pCa specimens. No high intensity epithelial staining was observed in BPH specimens. In 19% of pCa and 7% of BPH specimens 5alphaR1 enzyme activity was detected. CONCLUSIONS: The presence of increased 5alphaR1 in some prostatic malignancies suggests that it is worthwhile to investigate the use of a dual 5alphaR inhibitor to prevent or treat early stage prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2004

Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a comparative study with prostate specific antigen parameters.

PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome 17p13.1 are currently the most common genetic abnormalities associated with many different types of human malignancies. Recently serum p53 antibodies (p53-Abs) have been detected in the serum of patients with various cancers. To evaluate the clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific antigen (PSA) parameters in patients with benign prostatic disease (BPD) and prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50 patients with BPD and 103 with histologically diagnosed prostate cancer, including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA kit. The clinical values of p53-Abs were compared with total PSA, PSA density (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA ratio using ROC curves. RESULTS: All patients with prostate cancer had significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD. While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with stage progression, serum p53-Abs were not related to clinical stage. The Gleason sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups. Patients with T1c cancer had significantly higher p53-Abs than those with BPD. According to ROC curve analysis to distinguish prostate cancer from BPD the p53-Abs titer had the greatest AUC in the overall patient population and in patients without digital rectal examination findings. CONCLUSIONS: These results suggest that p53-Abs might be helpful in the clinical decision to perform prostate biopsy. In the current study the serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.

Aged↗
PubMed1993

Mucins in prostatic intra-epithelial neoplasia and prostatic carcinoma.

A histochemical study of 27 well-differentiated prostatic carcinoma cases associated with prostatic intra-epithelial neoplasia (PIN) was carried out. In the histological areas examined a decreasing production of neutral mucin was found as follows: normal prostatic tissue (70%), prostatic carcinoma (55%), PIN 1 (50%), PIN 2 (30%) and PIN 3 (15%). A progressively increasing content of acidic mucin (AB 2.5) was observed in the areas of PIN 3 (25%), PIN 2 (35%) and prostatic carcinoma (70%), while it was absent in the areas of PIN 1 and normal prostatic tissue. Acidic mucin sulphated type (AB 1) was secreted only in PIN 3 (5%) and prostatic carcinoma (10%) areas. These data were correlated with the proliferative activity of PIN. It is postulated that the lower neutral mucin production by PIN 3 can be linked to the higher proliferative activity of this lesion. Moreover, the acidic mucin secretion by PIN and prostatic carcinoma is considered to be a further feature of these lesions.

Acid Phosphatase↗
PubMed1987

Tumour markers in prostatic carcinoma. A comparison of prostate-specific antigen with acid phosphatase.

A study was performed on 130 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. The results showed that all 30 normal controls below 40 years of age had values less than 10 ng/ml. Of the 40 patients with BPH, all aged over 40 years, 13 (32.5%) had raised levels above 10 ng/ml. In the 60 patients with prostatic carcinoma, all over 40 years, 24 had localised disease (MO) and 36 had metastatic spread (M1), as judged by isotope bone scan. In patients with MO disease, 16 (66.6%) had raised PSA levels compared with 34 (94.5%) of those with M1 disease. The corresponding figures for raised prostatic acid phosphatase (PAP) values were 4% in the MO group and 52.7% in the M1 group. PSA levels reflected neither the histological grade nor the local stage of the tumour and were of no value in estimating tumour burden. PSA was found to be a valuable index in the management of prostatic cancer because of this sensitivity. Stable disease not requiring hormonal manipulation was reflected by unchanging levels of PSA, whereas progressive disease requiring hormonal therapy was reflected by an alteration in the PSA levels corresponding to the patients' response. The same group of progressive disease patients showed only a 50% rise in serum PAP levels, confirming the greater sensitivity of PSA as a measure of prostate cancer. PSA measurements should be included in any further trials on prostatic carcinoma and should be regarded as a standard marker for evaluating response to therapy.

Acid Phosphatase↗
PubMed1989

Prostate specific antigen--a screening test for prostatic cancer?

A series of 287 patients referred by their family doctors with symptoms of bladder outflow obstruction were asked to attend the hospital for "pre-clinic" screening for carcinoma of prostate (CaP). Blood samples were collected from 211 patients and analysed for serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Thirty-six patients had a serum PSA greater than 10 micrograms/l and 7 had PAP levels greater than 5 iu/l. In no instance was the PAP elevated without an associated increase in PSA concentration. Patients with raised markers underwent further investigations which included prostatic biopsy and/or resection; 17 patients were proved to have carcinoma of the prostate, 9 of whom had distant metastases. The specificity of PSA for detecting prostate cancer in this study was 90% with a sensitivity of 89.5%, in contrast to values for PAP of 100% and 36.8%. The routine use of PAP as a marker for prostatic cancer should be abandoned. The use of PSA as a screening test in a group of patients with prostatism appears justified, but with a positive predictive value of only 47%, its use in a mass unselected screening programme is not recommended.

Acid Phosphatase↗
PubMed2000

Effect of inflammation and benign prostatic enlargement on total and percent free serum prostatic specific antigen.

OBJECTIVE: To analyze the influence of inflammation and benign prostatic enlargement on total and percent free serum prostatic specific antigen (PSA). PATIENTS AND METHODS: Total and free PSA serum levels were determined in 284 patients with no evidence of cancer in the sextant ultrasound-guided biopsy. Double antibody immunoradiometric assay Tandem and Tandem free PSA were used. Benign tissue without inflammation was found in 23.2% of the patients (group 1), while in 68.3%, it was associated with chronic prostatitis (group 2) and with acute prostatitis in 8.4% (group 3). RESULTS: Median serum PSA was 7.8 ng/ml in group 1, 6.7 ng/ml in group 2 and 6.4 ng/ml in group 3, p>0.05. Median percent free PSA was 14.1, 15.6 and 16.4%, respectively, p>0.05. Multiple linear regression analysis showed that prostatic size was the only significant contributor to serum PSA concentration. Moreover, total PSA and prostatic size contributed significantly to the percent free serum PSA. Inflammation had no significant influence on total or percent free serum PSA. CONCLUSION: Inflammation has an important prevalence in cancer-free prostatic biopsy specimens. It seems to have no significant influence on total and percent free serum PSA. However, prostatic size seems to be the major contributor.

Acute Disease↗
PubMed2005

Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study.

PURPOSE: Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP). PATIENTS AND METHODS: We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. RESULTS: In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P < or = .004), and biochemical progression (comparing prostate weight < 20 v > or = 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound-measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P < or = .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06). CONCLUSION: Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.

Humans↗
PubMed1994

Prostate-specific antigen and human glandular kallikrein: two kallikreins of the human prostate.

Prostate-specific antigen (PSA) is a 33 kD protein synthesized in the epithelial cells of the prostate gland. It is a serine protease that belongs to the subgroup of kallikreins, among which it is very similar to a putative enzyme called human glandular kallikrein (hGK-1). Although the hGK-1 enzyme remains to be characterized in vivo, the hGK-1 gene is expressed in the same prostatic epithelial cells as the PSA gene. Expression of the PSA gene is under complex control and the steady-state level of PSA mRNA is increased by androgens, and decreased by epidermal growth factor and activation of protein kinase C. This suggests the existence of several regulatory elements within the cis-acting control elements of the PSA gene. As a seminal serine protease, PSA has been shown to digest the high molecular weight seminal vesicle protein, seminogelin. However, it is likely that this does not constitute the only natural substrate of PSA, as PSA has been shown to degrade insulin-like growth factor-binding protein-3. Serum PSA concentrations are frequently increased in patients with prostatic cancer, but this is also the case in patients with benign prostatic hyperplasia. Thus, PSA measurements alone are not useful as a screening tool for undiagnosed prostatic cancer. However, serum PSA concentrations can be successfully used together with other methods in diagnosing prostatic diseases and in monitoring the successfulness of treatments for prostatic cancer.

Biomarkers, Tumor↗
PubMed2000

[Study of free to total prostate specific antigen ratio in the detection of patients with prostate cancer].

BACKGROUND: We investigated the clinical usefulness of free to total serum prostate specific antigen (PSA) ratio (F/T ratio) in order to improve the specificity of total PSA measurement for detecting prostate cancer. METHOD: In this study 129 patients with total PSA level 4-20 ng/ml underwent transrectal ultrasound guided sextant biopsy. Serum samples were assessed for total PSA, free PSA and the F/T ratio calculated. All patients were pathologically diagnosed as benign prostatic hyperplasia or prostate cancer. RESULTS: Of 129 patients 21 had prostate carcinoma (PCa) and 108 had benign prostatic hyperplasia (BPH) from the results of prostate biopsies. The mean of total PSA were not significantly different between men with PCa and with BPH. The mean of free PSA for PCa was significantly lower than that for BPH (p = 0.043). Furthermore, the mean of F/T ratio was significantly different between PCa and BPH group (p = 0.0014). The F/T ratio had a higher specificity than total PSA at all levels of sensitivity in detecting prostate cancers. Sensitivity, specificity and accuracy for cancer detection at a cut off 0.12 was 90.4%, 51.8% and 58.1%, respectively. Also, free PSA was as useful as F/T ratio for cancer detection when analyzed in receiver operating characteristic curves analysis. When determined the cut off number of free PSA at 0.78 ng/ml, the sensitivity, specificity and accuracy for cancer detection were 61.9%, 66.7% and 65.9%, respectively. CONCLUSION: This study indicated that the F/T ratio and free PSA could improve the specificity without impairing the sensitivity for detecting PCa in patients with 4-20 ng/ml of total PSA.

Aged↗
PubMed1999

Levels of expression of p27KIP1 protein in human prostate and prostate cancer: an immunohistochemical analysis.

p27KIP1 is a member of the CIP/KIP family of cyclin-dependent kinase inhibitory proteins that negatively regulate cell proliferation. Recent studies reported decreased p27 expression in breast and colon carcinomas and found that the loss of p27 is associated with a poor prognosis. We report here the results of our immunohistochemical analysis of p27 in human prostate cancer. Formalin-fixed, paraffin-embedded, whole-mount sections of prostate cancer from 73 selected patients treated by radical retropubic prostatectomy were obtained from the Department of Pathology, The Methodist Hospital, Houston, Texas. Ten histologically normal and nine high-grade prostatic intraepithelia neoplasia foci were selected from these whole-mount sections, and nine cases of transplant donor prostates were chosen as controls. Also, 10 prostate cancer metastatic lymph nodes were used to compare with the primary cancer group. Sections were immunostained with a monoclonal antibody against p27 protein using the avidin-biotin complex immunohistochemical method. Immunoactivity was evaluated without knowledge of follow-up and recorded as the p27 labeling index (LI) (defined as the percentage of p27-positive cells among epithelia of the same category). The p27 (LI) in normal prostatic epithelia was 86.4+/-3.5% (the mean +/- the standard error of the mean). In contrast, the p27 immunoreactivity was significantly lower in cancers (LI: 43.5 +/-3.7%, P < .001) and in the high-grade prostatic intraepithelial neoplasia group (LI: 59.3 +/- 3.2%, P < .05). Expression of p27 in the metastatic lymph node group was significantly lower than in the other groups, including the prostate cancer cases and the cases of high-grade intraepithelial neoplasia (LI, 7.0%; P = .05). There was no association of the mean p27 LI with progression after radical prostatectomy. Nonrecurrent cases, with a mean follow-up time of greater than 5 years (n = 45), equalled 41.9%; recurrent cases, with a mean follow-up time of 18.3 months (n = 28), equalled 40.0%. The mean p27 LI was not associated with pathologic stage. Organ-confined specimens (n = 21) equalled 34.2%; cases of extraprostatic extension (n = 24) equalled 46.5%; and samples showing seminal vesicle involvement (n = 14) equalled 47.6%. In 14 cases with lymph node metastases, the mean p27 LI was 48.1% in the primary cancer (P = .2322). There was no association of the mean p27 LI with the Gleason score (P = .4747) nor with the clinical stage (P = .9914).

Cell Cycle Proteins↗
PubMed2000

Interferon-gamma and its functional receptors overexpression in benign prostatic hyperplasia and prostatic carcinoma: parallelism with c-myc and p53 expression.

The therapeutic potential of IFN-gamma in prostatic cancer has been documented in several reports, although no immunohistochemical studies of this factor and its receptors in the prostate have been reported. The aim of the present study was to investigate the expression of IFN-gamma and its receptor components (IFN-gamma-Ralpha and IFN-gamma-Rbeta) in normal prostate, benign prostatic hyperplasia (BPH) and prostatic cancer (PC), as well as the possible relationship between this factor and the products of the p53 gene (the wild and mutant forms) and the oncogene c-myc, by means of immunochemical techniques (Western blot, ELISA, and quantification of immunostaining in histological sections). In normal prostate, IFN-gamma and its two receptors were expressed in the basal cells of the epithelium and some stromal cells. In BPH specimens, immunostaining of basal epithelial cells was significantly increased for IFN-gamma and its a receptor, whereas stromal cell immunostaining was significantly increased for IFN-gamma and its b receptor. In addition, columnar epithelial cells immunostained for IFNbeta-Rbeta. PC specimens differed from BPH specimens in the significantly increased immunostaining of epithelial cells for IFN-gamma and its two receptors, and the immunostaining of columnar epithelial cells for IFN-gamma-Ralpha. Immunodetection of wild-p53 was weak and limited to some stromal cells in the three types of specimens. Immunostainings for both mutant-p53 and c-myc were negative in normal prostate, and positive in the epithelium and stromal cells of both BPH and PC specimens. Immunostaining intensity in PC was significantly higher than in BPH. These observations suggest that the expression of both mutant-p53 and c-myc, together with other factors, might be involved in the development of prostatic hyperplasia and neoplasia, while the increased expression of IFN-gamma and its receptors could be regarded as an attempt, although insufficient, to inhibit the uncontrolled cell proliferation.

Aged↗
PubMedDate not supplied

[Multiple prostatic biopsies in the "gray zone" of the specific prostatic antigen].

PURPOSE: Aim of our study was to identify cases of undetected prostatic cancer in patients with normal findings at digital examination and transrectal US, and prostate specific antigen (PSA) values ranging 4-10 ng/mL. MATERIAL AND METHODS: Two hundred and ninety patients were submitted to transrectal US and random bilateral prostatic biopsy; 3 samples were collected from each side of the gland using 16-Gauge thru-cut needles. Of the 290 patients who gave fully informed consent, we selected 34 whose age ranged 56 to 76 years (mean: 64). Inclusion criteria were PSA 4-10 ng/mL, PSAD cut-off 0.15, free/total PSA ratio 15-25%, and normal findings at digital examination and transrectal US. PSA velocity was calculated collecting 3 blood samples every 30 days for 2 months. RESULTS: Five of the 34 selected patients (15%) had prostatic cancer, and 2 (6%) Pin (1 Pin 1 and 1 Pin 2). As for the other 27 patients, biopsy demonstrated 4 (12%) cases of prostatitis and 23 (62%) cases of BPH. PSA values increased in all patients with positive histology, versus only 6 (22%) of those with negative histology. PSAD was 0.15 or greater in 3 of 7 prostatic cancer patients. Free/total PSA ratio never exceeded the cut-off value. Gleason score ranged 2 to 4. CONCLUSIONS: Our findings confirm that prostatic biopsy can detect tumors also in areas which appear normal at transrectal US and digital examination, and that PSA rate increases in patients with positive histology. Finally, the actual clinical role of prostatic biopsy relative to all other diagnostic imaging techniques remains to be defined.

Aged↗