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Objective The clinical utility of the determination of serum prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) for the diagnosis of prostate cancer, especially in cases in the diagnostic gray zone, is still unclear. Material and methods With the use of a newly approved enzyme immunoassay for the detection of PSA-ACT, 907 sera, including those from non-urological benign and malignant diseases, were analysed. Results Serum values of PSA-ACT in non-prostate cancer males increased according to age from the 40s to 70s. The serum values were high only in the patients with prostatic diseases and, in prostate cancer patients, the values became high as the clinical stage progressed. By receiver-operating characteristic analysis significantly better results in PSA-ACT than total PSA were observed. In the group with a total PSA of 2-20 ng/ml, the detection of PSA-ACT showed better results, although not significantly so, than the free-to-total PSA ratio. Conclusions The detection of PSA-ACT showed a high clinical utility in the diagnosis of prostate cancer. Therefore, it may replace total PSA determination.

Background. Random systematic biopsy is widely utilized for the diagnosis of prostate cancer. The standard method seems to be transrectal ultrasonography (TRUS)-guided sextant transrectal biopsy. In this study, the results of a TRUS-guided transperineal technique were evaluated.

Objectives. To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. Methods. One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. Results. The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates ( P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. Conclusions. Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

The aim of the present study was to determine whether the serum levels of a bone formation marker, i.e., the carboxy-terminal propeptide of type I procollagen (PICP), and a bone resorption marker, i.e., the carboxy-terminal telopeptide of type I collagen (ICTP) have prognostic value in prostate cancer patients with bone metastasis, compared with alkaline phosphatase (ALP) and prostate-specific antigen (PSA).The serum levels of PICP, ALP, ICTP and PSA were examined in 116 untreated prostate cancer patients (40 patients with bone metastasis, 76 patients without bone metastasis), and the prognoses of the patients with bone metastasis were evaluated using univariate and multivariate analyses.The bone metastasis patients with low PICP or ALP values had significantly better outcomes compared to the bone metastasis patients with high PICP or ALP values. A multivariate analysis of PICP, ICTP, ALP, PSA and the patients' age revealed that PICP and patients' age were important prognostic factors for survival. The pretreatment levels of ICTP and PSA did not show any substantial relation to the prognosis of these patients.The results suggest that the pretreatment serum bone formation marker is an important prognostic indicator for prostate cancer patients with bone metastasis.

Objective: Patients with prostate cancer generally respond to androgen withdrawal therapy, but progression to androgen independence is frequently observed. To evaluate prognostic factors in metastatic prostate cancer, patients who had been treated with endocrine therapy were investigated. Methods: One hundred and thirty-nine patients with untreated metastatic prostate cancer (TxNxM1) who received endocrine therapy between 1986 and 1993 were included in the present study. Blood chemistry, histological grade, extent of bony metastases, clinical response to hormone therapy, and the prognosis of the patients were evaluated. Results: With univariate analysis, performance status, hemoglobin concentration, serum alkaline phosphatase, lactate dehydrogenase, histological grade, extent of bony disease, and response of prostate-specific antigen (PSA) at 3 months were shown to be significant prognostic factors. With multivariate analyses, response of PSA and histological grade were significant factors predicting prognosis. Conclusions: Patients whose PSA had not normalized 3 months after the start of endocrine therapy were in the high-risk group, and should be given more aggressive treatment.

In patients with progressive prostate cancer who have been treated with surgical or medical castration plus an antiandrogen, antiandrogen withdrawal can result in a significant decline in serum prostate-specific antigen (PSA). Although the incidence of antiandrogen withdrawal syndrome after combination treatment with the nonsteroidal antiandrogen flutamide has been thoroughly documented, the phenomenon clearly occurs in many other combination therapies and is presently being widely investigated. This paper would like to contribute to this effort by describing the endocrine withdrawal phenomenon in patients treated with combinations of castration plus chlormadinone acetate, ethynylestradiol or estramustine phosphate.Clinical records of 68 prostate cancer patients who had been treated with surgical castration plus the administration of chlormadinone acetate, ethynylestradiol or estramustine phosphate, and who had shown clinical progression associated with a steady increase in serum PSA, were investigated. Forty-one cases were evaluable for changes in PSA after discontinuation of the hormonal agents.Of 28 patients who had been treated with chlormadinone acetate, 12 (42.9%) revealed 50% or more decline in PSA level following withdrawal of the agent. Among these, 5 cases (17.9%) showed subjective and/or objective improvements. There was no significant difference in histological grade of the tumor at diagnosis, mode of progression, time interval from the start of endocrine therapy to discontinuation of the hormonal agents, or PSA level at withdrawal of the agents between patients who did develop antiandrogen withdrawal syndrome and those who did not.When a steady increase in serum PSA is noted in a prostate cancer patient who has been treated with castration plus a steroidal antiandrogen, discontinuation of the antiandrogen may benefit the patient.

Background: The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients. Methods: Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test. Results: The levels of PSA showed significant differences among 8 pairs of clinical stages, in contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis. Conclusion: PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.

Although several prognostic factors have been discussed, multivariate analysis that includes tumor marker doubling time has not yet been examined in patients with prostate cancer refractory to endocrine therapy. A number of conventional prognostic factors including doubling times of prostate-specific antigen and/or prostatic acid phosphatase were examined in 56 prostate cancer patients who were refractory to endocrine therapy, using univariate and multivariate analyses. On univariate analysis, 6 parameters (doubling times of prostate-specific antigen and prostatic acid phosphatase at the time of refractory status, performance status, duration from beginning of endocrine therapy to prostate-specific antigen/prostatic acid phosphatase failure, mode of recurrence, the presence or absence of prostate-specific antigen/prostatic acid phosphatase normalization, and alkaline phosphatase) were shown to be significant prognostic factors. On multivariate analysis, only performance status and doubling times of prostate-specific antigen and prostatic acid phosphatase were significant. These observations showed that the doubling times of prostate-specific antigen and prostatic acid phosphatase, calculated at the time of prostate-specific antigen/prostatic acid phosphatase failure by estimating serial prostate-specific antigen or prostatic acid phosphatase, were a valuable prognostic factor in patients with prostate cancer refractory to endocrine therapy.

A study was undertaken to evaluate the clinical usefulness of measurements of serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as parameters of bone metastasis in patients with prostate cancer. Serum PICP, ICTP, prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were evaluated in 82 patients with prostate cancer and 26 patients with benign prostatic hyperplasia (BPH). These markers were measured serially in 16 prostate cancer patients during treatment. The serum levels of PICP, ICTP, ALP, and PSA were significantly higher in prostate cancer patients with bone metastasis than in patients with either BPH or prostate cancer without bone metastasis. Although the rate of detection of bone metastasis with PICP and ICTP was slightly lower than that with PSA determined by the receiver operating characteristic curve, the correlation between both PICP and ICTP and the extent of disease was much higher than that of PSA. PICP and ICTP levels varied with ALP and PSA levels, the patient's clinical course after the start of endocrine therapy and the progression of bone metastasis. The levels of PICP and ICTP did not change substantially in patients who developed local regrowth or lymph node metastasis, and decreased as bone metastases responded to radiotherapy. PICP and ICTP thus reflect the metastatic burden in bone and are useful for monitoring the response of bone metastasis to therapy.

BACKGROUND Patients with prostate carcinoma generally respond to androgen withdrawal therapy, but subsequent progression to androgen-independence is frequently observed. Since androgen receptors play a key role in androgen action, the ratio of androgen receptor-containing cells in cancerous tissues was determined by immunohistochemical staining of prostate biopsy specimens for comparison with the outcome. METHODS Sixty-two patients with untreated Stage D2 prostate carcinoma who received endocrine therapy between 1986 and 1992 were included in the present study. Biopsy tissue was stained with anti-human androgen receptor antibody, and the ratio of positively stained cells was estimated by counting 700 to 1000 cancer cells from each patient. Histologic grade, extent of bone metastases, clinical response to endocrine therapy, and outcome, were compared with androgen receptor content. RESULTS Cancers with a low Gleason score had a significantly higher androgen receptor content than those with a high Gleason score. Androgen receptor content was not significantly correlated with extent of disease or tumor marker response at three months. Patients with 48% or more androgen receptor positive cells had a statistically significant better outcome, in terms of both progression free and cause-specific survival, than patients with less than 48% androgen receptor content. Multivariate analysis demonstrated that androgen receptor content, extent of disease, and tumor marker response at three months were significant predictors of outcome. CONCLUSIONS Androgen receptor content measured immunohistochemically is a useful prognostic indicator for patients with Stage D2 prostate carcinoma treated with endocrine therapy. Cancer 1996;77:934-40.

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple genetic loci may result from mismatch repair errors, and occurs in hereditary nonpolyposis colorectal carcinoma and certain sporadic cancers. To examine microsatellite instability during the pathogenesis of human prostate cancer, we screened 48 prostate cancer cases (20 stage B, 10 stage C and 18 endocrine therapy-resistant cancer-death cases) for replication error at 17 microsatellite marker loci on 9 chromosomes. Microsatellite instabilities were found in 7 of 48 cases (14.6%), and all 7 cases showing the instability were poorly differentiated adenocarcinomas. Moreover, microsatellite instabilities were more frequently observed in cancer-death cases (6/18, 33%) than in stage B + C cases (1/30, 3.3%). These data suggest that microsatellite instability is an important genetic change related to the progression of a subset of human prostate cancer cases. It is suggested to be associated with extensive, concurrent molecular changes including androgen receptor gene mutations, as well as frequent loss of heterozygosity at chromosomal regions 8p, 10q, and 16q.

Objectives A case report is presented of 2 patients whose levels of serum prostate-specific antigen (PSA) improved after the withdrawal of a steroidal antiandrogen. Methods Two cases with prostate cancer had been treated with surgical castration and the steroidal antiandrogen chlormadinone acetate (CMA), and, on disease progression, the administration of CMA was terminated. Results Following withdrawal of CMA, a fall in PSA levels and remarkable clinical improvement were observed in both cases. One patient revealed a decrease and the other an increase in serum prostate acid phosphatase after the discontinuation of CMA. Serum levels of testosterone, prolactin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione were not significantly elevated after CMA withdrawal. Conclusions Withdrawal of the steroidal antiandrogen CMA resulted in a decline in PSA levels and clinical improvement in prostate cancer patients with disease progression. Changes in testosterone, prolactin, or adrenal androgens were not a cause of the antiandrogen withdrawal syndrome.

To compare levels of gamma-seminoprotein (gamma-Sm) assayed by original and revised assay systems, blood was obtained every 4 h over a 32-h period from 8 untreated prostate cancer patients. Serum levels of prostate specific antigen (PSA) were also examined. In 6 patients, the coefficient of variation (CV) of the serum levels assayed by the revised assay was significantly different from that of the intra-assay samples. In contrast, the CV of the gamma-Sm serum levels assayed by the original assay differed significantly from that of the intra-assay samples in only 2 patients. The fluctuations in gamma-Sm assayed by the revised assay were, at least in part, similar to those of the PSA serum levels in all patients. The mean CV of the gamma-Sm serum levels assayed by the revised assay was significantly larger than that for levels measured by the original assay. After treatment, the rate of decrease in gamma-Sm serum levels determined by the original assay differed from that in the serum levels of PSA and prostatic acid phosphatase. These results indicate that the original assay for gamma-Sm do not detect diurnal differences in serum gamma-Sm levels, even at levels below 20 ng/ml. These observations indicate that the analysis of data obtained using the original gamma-Sm kit should be interpreted with caution.

Genetic alterations of ras oncogenes (K‐, H‐ and N‐ras) and adenomatous polyposis coli (APC) gene in tissues of prostate cancer from Japanese patients were examined using PCR‐SSCP (polymerase chain reaction‐single strand conformation polymorphism) analysis and direct sequencing. Tissues from 8 cases of untreated stage B prostate cancer surgically removed and from 10 cases of endocrine therapy‐resistant metastatic disease obtained at autopsy were used in the present study. In four out of 18 cases (22%), ras point mutations were found, two in either codon 12 or 61 of K‐ras and two in either 13 or 61 of H‐ras. These point mutations were detected in one of the stage B cases (13%) and in three of the autopsy cases (30%). All these cases were poorly differentiated adenocarcinoma. In autopsy cases showing ras mutation in cancerous prostate, the same alteration was observed in metastatic tissues. No APC gene mutation was detected in any sample, although polymorphism was found in some cases. These results indicate that ras oncogene mutations are related to the progression of prostate cancer, whereas APC gene alteration is not involved in tumorigenesis and development of this cancer.

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an α1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia. © 1994 Wiley-Liss, Inc.

An inhibitory effect of TZP-4238, a newly synthesized antiandrogen, on the growth of Dunning R3327 rat prostatic tumor was studied and compared with that of chlormadinone acetate (CMA). TZP-4238 markedly suppressed the growth of R3327 tumor. The inhibitory effect of TZP-4238 on the tumor was more potent than that on the prostate. While the inhibitory effect of TZP-4238 on the weight of the ventral prostate was about 6 times as great as that of CMA, the suppressive effect of TZP-4238 on tumor weight was about 40times as great as that of CMA. Serum levels of testosterone and dihydrotestosterone showed no obvious changes after the administration of either TZP-4238 or CMA. The inhibitory effect of TZP-4238 on the growth of R3327 tumor indicated the application of the compound to human prostatic cancer.

Background: The aim of this study was to investigate the influence of osteoarthritis of lumbar vertebrae on serum bone formation and resorption marker levels of patients with benign prostatic hypertrophy (BPH). Methods: Serum levels of carboxyterminal propeptide of type I procollagen (PICP), alkaline phosphatase (ALP), carboxyterminaltelopeptide of type I collagen (ICTP), and prostate-specific antigen (PSA) were examined in 40 patients with BPH, and the presence of osteoarthritis at the lumbar vertebrae of the patients was evaluated by plain x-ray-p. Results: Findings of osteoarthritis were observed in 23 of the 40 patients (58%), and 10 of the patients had severe osteoarthritis (involving at least 2 lumbar vertebral bodies). The serum levels of PICP, ALP, ICTP, and PSA of the patients without osteoarthritis findings were not different from those of the patients with osteoarthritis or severe osteoarthritis. Conclusion: The influence of osteoarthritis on serum bone formation and resorption marker levels of patients with BPH appears to be rather slight, if there is any influence at all.

Background: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. Methods: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM1) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. Results: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. Conclusions: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.

Purpose: The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. Methods: From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50–66.6 Gy. Results: In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6–80 months (mean ±± ± SD: 33.9 ± 22.9 months). The follow-up period after irradiation was 7–64 months (mean ± ± ± SD: 25.4 ± 18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. Conclusions: In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time.

BACKGROUND Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover. Prostate 38:28–34, 1999. © 1999 Wiley-Liss, Inc.

Objective: The mode of progression in patients with prostate cancer with metastasis to nonregional lymph nodes was examined in order to know whether the site of metastasis effects the prognosis of prostate cancer. Methods: From 1986 to 1995 at the Chiba University Hospital, 205 cases of prostatic cancer with distant metastases were experienced. In 17 of them, nonregional lymph node metastases were observed at the diagnosis, of whom 10 also had bone metastases. Results: There was no statistical difference in prognosis between 17 patients with nonregional lymph node metastases and remaining 188 patients with metastatic prostate cancer. In all patients metastasized to nonregional lymph nodes, serum prostate-specific antigen and/or prostatic acid phosphatase levels were elevated. Anti-androgen therapy was effective in 15 cases and 5-year survival rate was 45.8%. Patients without bone metastases at the initial diagnosis could survive longer than those with metastases to bone (p < 0.05). Conclusions: From these observations, endocrine therapy was effective even in patients with distant lymph node metastases.

To evaluate the relationship between prostate-specific antigen (PSA) levels and prostate volume and age in a mass screening for prostatic disease, a total of 1,162 examinees from one Japanese prefecture who were over 45 years of age underwent a mass screening for prostatic disease that used the Hybritech (Tandem®RIA) kit, and the prostate volume was estimated by transabdominal ultrasonography. Differences among several groups of men according to prostate volume and age were examined by multiple comparisons using ranks. When some subjects visited several times, the data of the first visit were adopted only. The total number of individual subjects in this study was 589 men. The multiple comparisons using ranks and 10-year age brackets revealed that the levels of PSA showed significant differences between only two pairs of groups stratified by age. In contrast, the levels of PSA showed significant differences among seven pairs of groups stratified by the prostate volume according to 10-ml brackets. When a logarithmic transformation of the serum levels of PSA was used, the results showed the same tendencies. From the results of the present study, it can be said that the PSA reference range calculated with stratified prostate volume might be more useful in the detection of prostate cancer than that calculated with stratified age.

We investigated the usefulness of two biochemical markers of bone formation (PICP, the carboxy-terminal propeptide of type I procollagen, and bone ALP, bone-derived alkaline phosphatase) and a marker of bone resorption (ICTP, the carboxy-terminal telopeptide of type I collagen), to determine whether the presence of bone metastasis in prostate cancer could be evaluated and the extent of bone metastasis could be stratified by the serum levels of these markers, compared to total alkaline phosphatase (T-ALP) and prostate-specific antigen (PSA). The serum levels of PICP, bone ALP, ICTP, T-ALP and PSA were significantly higher in patients with both prostate cancer and bone metastasis (n=49) than in patients with benign prostatic hyperplasia (n=35) and patients with prostate cancer without bone metastasis (n=70). The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic curves. The serum marker levels were compared as a function of metastatic burden in bone (i.e., the extent of disease, EOD grade). We found that bone ALP is the most suitable marker for evaluating bone metastasis, especially for stratifying the degree of bone metastasis. Both PICP and ICTP were useful in this respect, but rather inferior to bone ALP. T-ALP had the lowest ability for detecting bone metastasis, but its correlation with the EOD grade was excellent, second to that of bone ALP. PSA showed limited reliability for stratifying the extent of bone metastasis.

Background: Various risk factors have been investigated concerning the etiology of prostate carcinoma, but many questions about the significance of the risk factors remain unanswered. To evaluate the relationship between smoking and obesity in prostate cancer, a case-control study was performed. Methods: Between 1986 and 1995, 329 patients with untreated prostate cancer and 188 patients with benign prostate hyperplasia (control patients) were evaluated according to their smoking habits and the degree of obesity. Also, the progression of prostate cancer in relationship to smoking and obesity was examined. Results: Smoking and obesity were not risk factors for the development of prostate cancer (odds ratio, 0.986, 0.836; 95% confidence interval, 0.69-1.41, 0.57-1.24, respectively). Nor were smoking or obesity a risk factor for survival in stage D2 patients, however, in stage B1-D1 patients, obese men had a tendency for disease progression. Conclusion: This study demonstrated that neither smoking nor obesity increase the risk of developing prostate cancer, or the risk of disease progression in prostate cancer patients. However, obese men have a tendency for progression of stage B1-D1 prostate cancer although further studies are necessary to confirm this finding.

BACKGROUND We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. METHODS Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. RESULTS Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.

Background The objective of this study is to evaluate the prognosis of carcinoma of the prostate presenting as non-regional superficial lymphnode metastasis. Methods From 1986 to 1996 at the Chiba University Hospital, 205 cases of prostatic cancer with distant metastasis were experienced. Results In nine of them, non-regional lymphnode metastasis was observed at the diagnosis. In all of them, serum prostate specific antigen and/or prostate acid phosphatase levels were elevated. In eight of nine cases, cancer nodule was detected by digital rectal examination. Anti-androgen therapy was effective in eight cases and five year survival rate was 56%. Conclusion From these observations, prostate cancer should be considered when superficial lymphnode was enlarged.

Background: This study was designed to evaluate the distribution of prostate-specific antigen (PSA) levels of men in a mass screening program for prostatic disease. Methods: A total of 763 men over 40 years of age underwent mass screening for prostatic disease in a lapanese prefecture using the highly sensitive Eiken kit and the Hybritech (Tandem-R) kit. The screening tests consisted of serum PSA determination, digital rectal examination, a questionnaire on symptoms, evaluation of prostate volume, and determination of the obesity rate. Results: Serum PSA levels of all subjects were measured with both kits. The correlation between the values obtained by the Eiken kit and those of the Tandem-R kit was high (r = 0.990), but the values of the former were slightly higher than those of the latter. Serum PSA weakly correlated with age, however, when estimated within decade age brackets, the levels of PSA showed significant differences among only 1 pair of groups stratified by age. In contrast, the levels of PSA showed significant differences among 9 pairs of groups stratified by prostate volume. Conclusion: A highly sensitive assay kit is useful to evaluate both the distribution of PSA levels and the relationship of PSA values to age and prostate volume of men in mass screening programs for prostatic disease, since approximately 40% of the subjects who underwent the present mass screening showed PSA values under 1 .O ng/mL, which have been the the lower limit of detection of many PSA kits. Int J Urol 1997;4:269-273

The growth of prostate cancer is androgen responsive, and androgen receptor (AR) is thought to play an important role in the development of this cancer. Recently, some reports demonstrated that AR gene mutations were detected in human prostate cancer tissues. We have previously reported that one of eight endocrine therapy-resistant prostate cancer cases showed AR gene mutation [Suzuki et al: J Steroid Biochem Mol Biol 46:759-765, 1993]. To further investigate structural abnormality of the AR in a large number of human prostate cancers, exons B-H encoding DNA-and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing. Tissues surgically removed from 30 cases of stage B or C prostate cancer and from 22 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Three out of 22 cancer death cases (14%) revealed AR gene mutations, one of which contained two different mutations-exon D in cancerous prostate and exon H in metastatic tissues. In the other two cases, AR gene mutations in exon H were found in metastatic tissues. All three cases in metastatic tissues showed the same mutation at codon 877 (877Thr-->Ala). In stage B or C cancer tissues and the other cancer death samples, no AR mutation was detected. The mutation in exon H was identical to that reported in a human prostate cancer cell line, LNCaP. These results indicate that AR gene mutation scarcely occurs in the early stage of prostate cancer and that the mutation is found in relation to endocrine therapy resistance. Two patients with an AR gene mutation at codon 877 revealed a remarkable fall in prostate-specific antigen after withdrawal of antiandrogen. Data on the other case were not available. These results indicate that a codon 877 mutation in the AR gene in advanced prostate cancer evokes the antiandrogen withdrawal syndrome. To our knowledge, this report is the first description of relationship between an AR mutation at codon 877 and the antiandrogen withdrawal syndrome.

To determine the changes in histologic features during the course of prostate cancer under longterm endocrine therapy, histologic grade and argyrophilic nucleolar organizer regions (AgNORs) were examined in specimens before treatment, at relapse, and at cancer death. A total of 29 patients who had received endocrine therapy and died of prostate cancer were evaluated. Among the 29 cases, biopsy tissues before treatment (25 cases) and during progression from endocrine therapy (10 cases) were compared with autopsy specimens. Histologic grade was determined by the method of Gleason, and the number of AgNORs in cancer cells was counted. Survival of the patients was compared with the histologic features. There was a tendency for a higher grade of cancer during the clinical course. Moreover, a statistically significant increase in the number of AgNORs was observed from pretreatment biopsy to autopsy. Upon comparison of metastatic sites with local cancer at autopsy, no significant difference was noticed in terms of histologic grade or AgNOR count Although there was no correlation between the number of AgNORs and survival after initial treatment, an inverse relationship was demonstrated between the number of AgNORs and survival in patients with systemic progression after endocrine therapy. In conclusion, prostate cancer shows an increase of malignant potential, as assessed by histologic grade and the number of AgNORs. Patients with cancer of high proliferative ability showing high grade and greater numbers of AgNORs have poorer prognosis from progression.

It is of clinical importance to control pain in the management of patients with endocrine-therapy-refractory prostate cancer. To evaluate factors influencing the manifestation of pain and the relationship between characteristics of pain and prognosis, patients with pain from bone metastasis were analyzed. A total of 48 patients with endocrine-therapy-refractory prostate cancer, who showed progression of bone metastasis and were followed-up until death, comprised the present study. The patients were divided into three groups according to the grade of pain: no need for analgesics, a need for non-opioid analgesics, and a need for opioid analgesics. The time interval between the diagnosis of the endocrine-therapy-refractory state and the requirement for analgesics was estimated. Survivals from the endocrine-therapy-refractory state were calculated according to the grade of pain or the time interval to requirement for analgesics. In addition, the extent of disease, the doubling time of tumor markers at the refractory state, any change of alkaline phosphatase, and other prognostic factors were examined in relation to pain. All 22 endocrine-therapy-resistant cases at initial treatment and 18 of 26 (69%) relapsed cases required analgesics during the clinical course until death. No difference in survival was observed between the grades of pain. The patients who needed analgesics within 1 year after becoming refractory to endocrine therapy showed significantly shorter survival than those without or with analgesics more than 1 year later. Although the time elapsing before analgesics were needed was not related to the extent of disease, the patients who showed a shorter doubling time for tumor markers and/or an exponential increase in alkaline phosphatase tended to require analgesics within 1 year. In endocrine-therapy-refractory prostate cancer, the early requirement for analgesics suggests poor prognosis, and the onset of pain may be attributable not to the extent of the disease but rather to the rapid expansion of bone metastasis.

The efficacy of aspiration cytology, using Franzen method and echo-guided aspiration for prostate cancer was examined to 102 patients under saddle-block anesthesia in urological clinic of Chiba University Hospital. Between 1990 and 1993, 77 cases out of 102 patients were diagnosed histologically as prostate cancer by needle biopsy and 90% of them were coincidental with findings of aspiration cytology. Looking at histological grades, well differenciated cancer was shown to yield low positivity compared with moderately and poorly differentiated cancer. Positive rate showed similar when grade of specimens from needle biopsy was classified with Gleason pattern. Neither T category nor method of aspiration between Franzen and echo-guided methods influenced positive rate of aspiration cytology. On aspiration cytology, its grading revealed 60% of coincidence with that obtained by histological method. When counting more than 300 scattered cells, 90% of coincidence was achieved with histological grading. It is concluded that aspiration cytology is efficient for diagnosis of prostate cancer.

To study the disease progression in stage A prostate cancer, 212 patients with stage A from a group of 3370 patients who underwent transurethral resection of the prostate, or subcapsular prostatectomy during the period 1972-1991 were followed. The stage A cases were subdivided into 103 A1 patients and 109 A2 patients and their subsequent course was followed for an average of 41.7 months (6-174 months). Progression to clinical cancer was found in 12 patients, 2 from A1 and 10 from A2 groups. This progression was evident 40.5 months (14-130 months) after prostatectomy. Eight (67%) of these cases responded to endocrine therapy. The rate of expression of ras p21, and the number of argyrophilic nucleolar organizer regions in stage A cancer cells were greater in progressing than in non-progressing cases. These results indicate that stage A cancer with progression arises mainly from the A2 subgroup and exhibits a distinctly proliferative potential even at small foci.

Prostate specific antigen (PSA) levels after total prostatectomy or radiation therapy to localized prostate cancer and also during endocrine therapy are within normal range. Therefore, it is necessary to use hyper sensitive PSA assay kits for early detection of relapse. The present study was undertaken to evaluate two hyper sensitive assay kits (Delfia kit, lower limit 0.1 ng/ml, Kabi Pharmacia Diagnostics Co. and Markit M kit, 0.5 ng/ml, Dainippon Pharmaceutical Co.) and to compare them with conventional PSA kit (Eiken Chemical Co., 1.0 ng/ml). Total of 291 sera were examined: patients consisted of 10 total prostatectomy+endocrine therapy, 9 radiation therapy+endocrine therapy, 5 radiation therapy alone and 44 endocrine therapy alone. Values of endocrine therapy alone were divided into two groups according to duration after start of treatment; more or less than 5 years. The following results were obtained. 1. In non-relapse patients after total prostatectomy+endocrine therapy and radiation+endocrine therapy, PSA showed under lower limit with hyper sensitive kit. On the contrary, conventional kit indicated more than 1.0 ng/ml. 2. Radiation therapy alone kept PSA in detectable range with hyper sensitive kit in spite of no sign of relapse. 3. In non-relapsed patients under endocrine therapy alone, long duration (more than 5 years after start of treatment) decreased PSA in non detectable values with hyper sensitive kits. In this case, conventional kit still showed PSA as more than 1 ng/ml. 4. Doubling time at relapse was estimated similar with Delfia kit and Markit M kit, and much longer with conventional kit. It is concluded that hyper sensitive kit is more useful to manage patients after therapy than conventional kit.

To estimate the growth rate of prostate cancer, the doubling times of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 51 patients: 44 were refractory to endocrine therapy, and 7 were in an untreated state. Since an exponential increase in PSA and PAP was observed in all patients, the doubling time was calculated from a semilogarithmic plot of the respective markers. PSA doubling time was almost identical with that of PAP. The tumor marker doubling time in untreated patients was approximately 10 times greater than that in the patients who were refractory to endocrine therapy. In endocrine refractory patients, the tumor marker doubling time in patients who showed deterioration of bone lesions was less than that in patients with local regrowth and/or lymph node metastasis. The prognosis of endocrine refractory patients from the time showing tumor marker failure was examined. The group showing the longest time (> 80 days) had better prognosis than that shown by the other groups with shorter doubling times. It is concluded that the determination of tumor marker doubling time is of value for measuring the growth rates of prostate cancer, and for assessing prognosis after relapse.

A randomized clinical trial of neoadjuvant endocrine therapy followed by either surgery or irradiation and a resumption of endocrine therapy for stages B2 and C prostate cancer has been in progress since 1989. A hundred patients entered the trial between 1989 and 1993, and 95 cases were evaluated. Forty-six patients received surgery and 49 were treated with irradiation. Neoadjuvant endocrine therapy for two months resulted in prostate shrinkage and prostate specific antigen lowering. Except for two patients, one dying of a progression of disease and the other of another concurrent cancer, all are alive with an average follow-up term of 25 (range 3-53) months. The good prognostic results obtained from both treatment groups at present seem to be due in part to the neoadjuvant endocrine therapy; but in order to reach a final conclusion further comparisons need to be made.

In order to evaluate the significance of repeat transurethral resection (TUR) in differentiating stage A1 prostatic adenocarcinoma from those with stage A2, we performed repeat TUR in 34 patients with an initial diagnosis of stage A1 prostatic adenocarcinoma. It was found that residual adenocarcinoma was present in five cases (14.7%), but the diagnosis was changed from stage A1 to stage A2 in only one case (2.9%). In one patient with final diagnosis of stage A1 carcinoma, bone metastases were detected seven months after the repeat TUR. It was concluded that repeat TUR for stage A1 prostatic adenocarcinoma did not yield clinically significant information.

To examine the natural course of human benign prostatic hyperplasia (BPH), cases in health care examination with or without slight urinary symptoms were examined by echography. In comparison with these cases, the size of the prostate was examined in patients who received prostatectomy. Prostatic sizes of health care cases varied widely along with increasing age, but could be divided into two groups: increasing or no-change. According to serial determinations of prostatic sizes in the increasing group, the annual growth rate of the prostate was calculated as 1.65 ± 1.13 and 0.85 ± 0.44 g in men

Objective. To clarify the relation between diurnal rhythm of serum levels of testosterone and two prostatic markers, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). Methods. Blood was obtained every four hours during a thirty-two-hour period from fourteen men with untreated prostate cancer. Results. Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients, respectively. About half of the remaining patients, the highest or nearly highest peaks of serum levels of PSA or PAP were ob served in the afternoon rather than the morning. In 3 patients, circadian rhythms were not observed in serum levels of PAP, but the fluctuation patterns were the same as those of testosterone and showed synchronous movement. In 7 patients, serum testosterone levels were followed by the same fluctuation pattern for either PSA or PAP after some time delay. Little change in serum levels of PSA was seen throughout the thirty-two-hour period despite large fluctuations of testosterone and PAP levels in 5 patients. Conclusions. Close relation between the fluctuation in serum levels of PSA and PAP, and that in serum levels of testosterone during diurnal periods could be considered. However, the relationship between serum testosterone levels and those of PSA and PAP was ambiguous because of both the difference in the time delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA despite obvious fluctuations in testosterone and PAP in some cases.

The effects of various chemotherapy regimens on endocrine-therapy-refractory prostate cancer were examined in 64 patients. Chemotherapy was started from the first evidence of relapse. The regimens of the initial chemotherapy were as follows: cisplatin (CDDP, 4 cases) and ifosfamide (4 cases) were given as single agents and vincristine, ifosfamide, and peplomycin (VIP, 8 cases); cyclophosphamide, doxorubicin, and CDDP (CAP, 14 cases); ifosfamide, doxorubicin, and CDDP (IAP, 24 cases); and etoposide, doxorubicin, and CDDP (EAP, 10 cases) were given as combinations. On the basis of the results, the patients were divided into two groups: single agents plus VIP and other combinations. In the CAP, IAP, and EAP groups, the cause-specific survival was similar, and the survival of these groups was longer than that of the single agents plus VIP group. Since patients with a long duration between the start of endocrine therapy and the start of chemotherapy were contained in the CAP, IAP, and EAP groups, comparison was performed without these cases. No difference was found between the two groups, suggesting that no superior regimen was found. The short-term effect was evaluated on the basis of the changes observed in prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels at 3 months after the start of chemotherapy, and patients showing a complete response, partial response, or no change on any of the regimens exhibited longer survival than did those with progressive disease. Since the PSA doubling time estimated before the chemotherapy correlated with the change in the PSA values due to the chemotherapy, the rate of proliferation of the tumor influenced the effect of the chemotherapy. Thus, this finding suggests that slowly growing cancers show a better response to chemotherapy than do rapidly proliferating ones.

Twenty seven patients with endocrine therapy relapsed prostate cancer were studied by measuring their prostatic acid phosphatase (PAP), prostate specific antigen (PSA), gamma-semino-protein (gamma-Sm) and alkaline phosphatase (ALP) serially before change of the treatment, and tumor marker doubling time was calculated. The exponential increase in PAP, PSA and gamma-Sm was observed in all patients and ALP showed a similar pattern in some. The values of PAP doubling time were the same as those of PSA, but gamma-Sm doubling time was slightly longer than the former ones. Tumor marker doubling time correlated with survival after the increase in markers, and also with time between the start of endocrine therapy and the increase in markers. Patients who showed either NC or PR to chemotherapy had a longer tumor marker doubling time than those with PD. In cases showing progression of bone metastasis, patients with exponential increase in ALP showed worse prognosis when compared with those showing other patterns. From these results, it was demonstrated that determination of tumor marker doubling time in patients with endocrine therapy relapsed prostate cancer was a valuable method to measure rate of regrowth, and to assess the prognosis after relapse.

Serum prostate-specific antigen (PA) values detected by a newly developed enzyme immunoassay (EIA, MARKIT-M PA) as a successor of MARKIT-F PA, which has been a leading kit in Japan, were evaluated for its role in the diagnosis of cancer of the prostate and follow-up of the patients afflicted with the disease. The system is one-step sandwich type EIA using horseradish peroxidase as a tracer and has 0.50-100 ng/ml of detectable range with small amount of sample volume (25 microliters) and reliable quality control data. Furthermore, serum PA values detected by the assay were almost equivocal to those detected by MARKIT-F PA. Serum PA values in prostate cancer patients (n = 122) were statistically higher than those in normal males (n = 90), urological malignancies other than prostate cancer (n = 48) or benign prostatic hypertrophy (BPH, n = 73). Even in the patients with stage A and B prostate cancer, serum PA values were observed to be statistically higher than those in BPH cases. If 3.6 ng/ml was used, which is normal value in MARKIT-F PA, as a cut-off value and BPH cases as a control, the sensitivity, specificity and efficacy for diagnosis of prostate cancer were 77.9, 91.8 and 83.1%, respectively, which showed the best results during the range examined. Serially determined serum PA values in following up the patients with prostate cancer were confirmed to be highly effective to evaluate treatment responses. These results suggest that MARKIT-M PA is thought to be one of the best tool for determination of serum PA values.

Bone scintigraphy of metastatic lesion on 128 patients with prostatic cancer were classified according to the proposal by Soloway et al (Cancer, 61; 195-202, 1988). Since all patients received endocrine therapy, the response to therapy and survival were examined in relation to bone lesion. In extent of disease (EOD) 1, main metastatic lesions were located in the pelvis, lumbar spine, and with increasing number of EOD, metastases in the upper spine, rib, and skull appeared. Longer survival were noticed in EOD 1, followed by EOD 2 and EOD 3, and EOD 4 revealed the shortest survival. The survival of EOD 2 was similar to thus of EOD 3. However, when grades of tumor were considered, moderately differentiated cancer showed longer survival than poorly differentiated cancer in EOD 2 and EOD 3. The response as assessed by bone scintigraphy following 6-month therapy was well correlated with the number of EOD. When individual items for evaluation of response were examined, the results of local response of the prostate and values of PAP showed good correlation with survivals, however, that of bone lesions with bone scintigraphy failed to show such a correlation with prognosis. Therefore, it is concluded that the therapeutic evaluation of bone lesions with bone scintigraphy is difficult to interpret 6 months after initiation of treatment.

Argyrophilic nucleolar organizer regions (AgNORs) were examined histologically in cells of benign hyperplastic and cancerous human prostates. Individual dots of AgNORs inside nucleus that were stained as separate granules or as parts of clusters were counted as one, and the average number of dots per cell was obtained by counting 100 nuclei. The number in epithelial cells was similar to that in stromal cells of hyperplastic prostates. In cancerous prostates, the number was larger than in hyperplastic prostates and increased along with upgrading. The number in incidental cancers was smaller than in clinical cancers as compared with cells of the same Gleason pattern. Number correlated with T factor, but not with N and M factors. Response to treatment and cause-specific survival in stage D2 patients receiving endocrine therapy did not correlate with number, although a relationship between Gleason pattern and survival was shown in these patients. It was concluded that AgNORs might not be an indicator to predict prognosis after endocrine therapy, since a number of AgNORs did not influence response to the therapy.

The clinical courses of bone metastases in 81 cases of prostatic cancer were examined using conventional X-ray. All patients received endocrine therapy as the initial treatment; castration and estrogen were given to 46 cases, castration and antiandrogen to 19, LH-RH analog to 11, flutamide to 5. The response to endocrine therapy was evaluated every 6 months after the start of the treatment according to National Prostatic Cancer Project criteria. The prognosis was calculated by cause-specific survival. The types of untreated bone metastases on X-ray were classified into five: sclerotic in 12 cases (15%), mixed but mainly sclerotic in 25 (31%), mixed but mainly lytic in 14 (17%), lytic in 8 (10%) and undetermined with positive scintigraphy in 22 (27%). Two mixed types showed more spread metastases and tendency of elevated prostatic acid phosphatase when compared with other types. Temporary enlargement of sclerotic area within 6 months after start of the treatment did not correlate with deterioration of disease. Remodeling of metastatic areas occurred 6-36 months after start of the treatment showed curative course and the prognosis of these groups were favorable. Most of lytic areas tended to sclerotic finding following endocrine therapy regardless of effects by endocrine therapy. Sclerotic and two mixed types showed better and worse tendencies, respectively. On viewpoint of remodeling, change of metastatic area and newly appearance of metastases, an evaluation criteria of response to the therapy was proposed, which showed good correlation with prognosis. From these observations, it was concluded that bone metastases tended from lytic to sclerotic changes and that lytic-sclerotic cycles occurred repeatedly along with disease progression regardless of effect to therapy. Remodeling seemed to be curative signs of metastatic area.

From 1977 to 1986, in the Chiba University Hospital, 107 cases of prostatic cancer with bone metastasis were experienced. In 10 of them spinal paralysis caused by spinal metastasis of prostatic cancer was observed. Untreated five cases received endocrine therapy. One of them also underwent spine laminectomy and spinal instrumentation and regained the ability to walk. But the other cases treated by endocrine therapy showed only insufficient improvement of paralysis. Five cases with spinal paralysis which were resistant to endocrine therapy were treated by chemotherapy or radiation to the site of bone metastasis. One of them underwent laminectomy and spinal instrumentation. However, most cases showed no improvement of paralysis. It is concluded that spinal surgery is recommended in untreated cases for the sake of quality of life, but in cases with hormone resistance spinal surgery should cautiously be applied.

Expression of ras p21 was examined with monoclonal antibody RASK-3 in normal, benign hyperplasic, and cancerous prostates. In patients with stage D2 disease who received endocrine therapy, the relation between ras p21 expression, response to therapy, and prognosis was studied. In these patients, R 1881-binding protein (androgen receptor and progestin-binding protein) was also examined. Non-cancerous cells and most cancer cells from stage A patients did not express ras p21, while expression increased with both higher staging and grading. Staging pelvic lymphadenectomy was done in some stage A2-C cases, and presence of nodal metastasis was correlated with ras p21 expressions in the primary tumours. In stage D2, there was no correlation between ras p21 expression and R 1881-binding protein. Response to therapy and survival did not correlate with expression of ras p21, but was influenced by presence of R 1881-binding protein.

Androgen receptor was detected immunohistochemically in benign as well as malignant prostatic tissues by using a monoclonal rat anti-human androgen receptor antibody (AN 1-15). In both benign and malignant cells, the androgen receptor was exclusively localized in nuclei. In hyperplastic prostate, the androgen receptor was stained in the glandular and the stromal cells. In the gland, cells facing the lumen were stained more intensively than those adjacent to the basal membrane. In cancer tissue, receptor-positive and -negative cancer cells were intermingled. The percent of strongly positive cancer cells was correlated inversely with grade. Relapsed cells showed a low population of strongly positive cells irrespective of grade.