Selective activation of the fatty acid synthesis pathway in human prostate cancer.

A substantial subset of breast, colorectal, ovarian, endometrial and prostatic cancers displays markedly elevated expression of immunohistochemically detectable fatty acid synthase, a feature that has been associated with poor prognosis and that may be exploited in anti-neoplastic therapy. Here, using an RNA array hybridisation technique complemented by in situ hybridisation, we report that in prostate cancer fatty acid synthase expression is up-regulated at the mRNA level together with other enzymes of the same metabolic pathway. Contrary to the observations that in many cell systems (including androgen-stimulated LNCaP prostate cancer cells) fatty acid and cholesterol metabolism are co-ordinately regulated so as to supply balanced amounts of lipids for membrane biosynthesis, storage or secretion, no changes in the expression of genes involved in cholesterol synthesis were found. These findings point to selective activation of the fatty acid synthesis pathway and suggest a shift in the balance of lipogenic gene expression in a subgroup of prostate cancers.

Modern prostate brachytherapy. Prostate specific antigen results in 219 patients with up to 12 years of observed follow-up.

BACKGROUND: The purported lack of long term modern prostate brachytherapy outcome data continues to lead many physicians to recommend other, more traditional treatments. This concern for long term results has encouraged the authors to supplement their earlier 10-year follow-up of patients receiving brachytherapy; in the process, an additional 77 patients (> 50%) were added to the original cohort, and the follow-up time was increased by 2 years. METHODS: Between January 1987 and September 1989, 229 patients with T1-T3 prostate carcinoma underwent transperineal prostate brachytherapy using iodine-125 (I-125). No patient received adjuvant hormone therapy. The median Gleason sum was 5 (range, 2-10). Of these patients, 147 were determined to have a high probability of organ-confined disease and were treated solely with an I-125 implant. The remaining 82 patients were determined to be at increased risk for extracapsular disease and received pelvic external beam radiation in addition to brachytherapy. All patients were followed continuously. Failure was defined as a positive biopsy, radiographic evidence of metastases, or three consecutive rises in prostate specific antigen (PSA) levels as defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus article. RESULTS: Excluding deaths from intercurrent disease, the median follow-up was 122 months (range, 18-144 months). Fourteen patients were excluded from analysis due to insufficient follow-up. Adopting the ASTRO definition of failure resulted in minimal change in survival when compared with the authors' previous study, which used a PSA level > 0.5 ng/mL as the failure point. Observed 10-year disease free survival (DFS) for the entire cohort was 70%. In the brachytherapy only group, the observed 10-year DFS was 66%, whereas those patients treated with the addition of external pelvic radiation achieved a DFS of 79%. None of the patients who were followed for the full 12 years failed between Years 10 and 12. Only 25% of the failures observed occurred > 5 years after treatment, thus confirming the durability of brachytherapy. CONCLUSIONS: Prostate brachytherapy provides excellent long term disease control with few late failures reported in the authors' program. The addition of external beam radiation appears to confer survival advantages in selected patients. Using the ASTRO failure criteria for long term follow-up resulted in no significant difference compared with using a PSA failure point of 0.5 ng/mL.

Follow-up ProstaScint scans verify detection of occult soft-tissue recurrence after failure of primary prostate cancer therapy.

BACKGROUND: A reliable imaging modality is required to uncover occult soft- tissue recurrence after failure of primary prostate cancer therapy. This retrospective study was done to evaluate the ability of the (111)Indium-labeled monoclonal antibody (ProstaScint(R)) scan in detection of prostatic bed recurrence and/or metastases to regional and/or distant lymph nodes. METHODS: One hundred sequential patients were evaluated with repeated ProstaScint(R) scans because of evidence of recurrence during the course of their disease. These 100 patients were followed closely from November 1994 and April 1999, and had concurrent bone scans and serum prostate-specific antigen (PSA) evaluations. They have had hormone therapy (n = 53) and/or experienced a rising PSA after radical prostatectomy (n = 38) or after radiation therapy (n = 56). Scan images were scored 0-3, where score 0 = negative, score 1= prostate bed uptake, score 2 = regional lymph node uptake, and score 3 = distant lymph node uptake. In each patient, the uptake of the follow-up scan(s) was compared to that of the initial scan. RESULTS: The median age was 70 years (range, 45-87), and 23 patients had a positive bone scan. The average PSA was 40.5 ng/ml (standard deviation, 223.5). There was 257 scans representing 100 patients. All patients had at least 2 scans, 35 patients had 3 scans, and 11 patients had 4 scans. No individual exhibited detectable adverse clinical reactions during or after the scan. The findings of the initial and consecutive scans were anatomically consistent in 79%, whereas in 21% there were skip metastases. In 24 patients the lesions progressed by scan and PSA, 10 patients showed progression of scan but no PSA progression, 49 patients showed no change, and 17 patients showed a remission related to adjuvant therapy. CONCLUSIONS: The consistency on repeating the scan (79%) and the high percentage of patients showing persistent uptake at the prostate bed (43%) as well as the percentage of detection of regional nodes (20%) and distant nodes (32%) reflects the importance of using the ProstaScint(R) scan in finding occult recurrences after primary treatment failure of prostate cancer. These results are similar to those reported earlier in autopsy series studies in similar populations.

Prostate-specific membrane antigen (PSMA): current benefits and future value.

We will review the evolution, benefits, and limitations of PSMA testing in the past, as well as its current and future value. Prostate cancer has been the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. It has a wide spectrum of biological behavior between latent (indolent) and progressive (aggressive). Further identification of prostate-specific membrane antigen (PSMA) as a prognostic proliferation marker may enhance our understanding of the types of prostate cancer. A review of PSMA testing in the past as well as currently was conducted. Studies were reviewed that deal with detection of PSMA in serum and seminal fluid, reverse transcriptase-polymerase chain reaction (RT-PCR), immunoscintigraphy, and immunohistochemical assays. PSMA is expressed primarily in benign and cancerous prostatic epithelial cells. It is up-regulated in hormone resistant states, and in metastatic situations or other clinical situations where there is tumor recurrence or extension. Based on current results, PSMA detected in the serum by western blotting can assist in the identification, staging, and monitoring of metastatic prostate cancer. In addition, PSMA shows a promising role in directed imaging and therapy of recurrent or metastatic disease.

Detection of extraprostatic prostate cells utilizing reverse transcription-polymerase chain reaction.

This article reviews the utility of reverse transcription-polymerase chain reaction (RT-PCR) in prostate cancer. RT-PCR aims to detect occult micrometastases in non-prostatic sites. Due to its exquisite analytical sensitivity, RT-PCR is able to amplify and detect even low-level, prostate-specific messages present at these extraprostatic sites. In recent years, a fair amount of data on the clinical utility of the technique had been reported. The target tissues under investigation are peripheral blood, bone marrow aspirate, and lymph nodes. Favorite markers of choice are prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and human glandular kallikrein-2 (hK2). False positives among negative controls are low. For the most part, RT-PCR is inadequate in detecting tumor cells in the peripheral blood from patients who are known to have metastatic prostate cancer. All studies showed that RT-PCR could detect PSA, PSMA or hK2 mRNAs in the circulation of patients who have organ-confined or extraprostatic disease. Most studies showed that RT-PCR utilizing current markers could not be used as a prospective test to diagnose prostate cancer. However, a few studies also showed that the detection rate could be predictive and sensitive enough to differentiate patients with organ-confined disease from those with extraprostatic disease. Data from PSA- or PSMA-RT-PCR using lymph nodes as the tissue source is more encouraging. RT-PCR was able to detect PSA and/or PSMA positive samples that have not been detected by conventional pathology.

Modern prostate brachytherapy.

Of all the treatment options available for men with organ-confined prostate cancer, brachytherapy--permament implantation of radioactive seeds into the prostate gland--is the least disruptive for the patient, both physiologically and practically. Early brachytherapy represents the oldest technique for delivering radiation to the prostate gland, preceding external beam therapy of the prostate by several decades. Although there have not been, and are not likely to be, any definitive randomized studies comparing radical prostatectomy, external beam radiotherapy, and brachytherapy, treatment decisions will continue to be made on the basis of patient and physician preferences in conjunction with clinical probabilities. Long-term results in this series show that monotherapy with seed implants achieved disease-free survival of 66%; moreover, 79% of patients with higher grade disease who were treated with a combination of brachytherapy and external beam radiation also experienced long-term disease-free survival. The following article provides a brief historical review of prostate brachytherapy, rationale for treatments, patient selection criteria, up-to-date implant techniques, and long-term (12-year) outcome results.

Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses. RESULTS: Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance. CONCLUSIONS: Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.

Vaccine therapy for prostate cancer.

Vaccine therapy may provide an alternative for prostate cancer patients whose disease no longer responds to hormone therapy. Administration of dendritic cells pulsed with prostate-specific membrane antigen (PSMA) induces cellular immune responses against the tumor with virtually no adverse effects. About 30% of the evaluable patients were identified as partial responders, based on the National Prostate Cancer Project (NPCP) criteria. In addition, there was a 50% decrease of serum prostate-specific antigen or resolution of previously measurable lesions on imaging. Dendritic cell vaccine therapy may have a synergistic effect, when combined with other therapies.

Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen.

BACKGROUND: Current statistics indicate that prostate carcinoma is the most common form of cancer diagnosed in American men, resulting in the second highest cancer death rate. Early diagnosis and accurate staging are imperative given that there is little effective treatment for metastatic disease, especially after androgen deprivation therapy fails. Identification of new biochemical markers for disease progression will provide important tools for diagnosis and monitoring. One such potential marker is prostate specific membrane antigen (PSMA). METHODS: A review was conducted to identify reports concerning evaluation of diagnostic applications of PSMA. RESULTS: PSMA is a membrane-bound glycoprotein that is highly restricted to the prostate. Immunohistochemical findings indicate that PSMA is a marker of epithelial cells of the prostate. This expression is increased in association with prostate carcinoma, particularly in hormone-refractory disease. Given its membrane-bound character, PSMA has been exploited as a marker for tumor detection by immunoscintiscanning with the 111In-labeled anti-PSMA monoclonal antibody 7E11.C5. Increased concentrations of 7E11.C5-reactive antigen are present in the serum of prostate carcinoma patients compared with healthy individuals; also, hematogenous circulating prostate carcinoma cells are detectable with reverse transcriptase-polymerase chain reaction analysis with primers specific for PSMA. New monoclonal antibodies specific for extracellular portions of the PSMA molecule currently are being utilized in applied studies. CONCLUSIONS: PSMA is a widely used marker for prostate epithelial cells. Its up-regulation in association with cancer, particularly in advanced cancer, is ideal for application as a prognostic marker. A variety of promising clinical applications utilizing PSMA have been or are being developed. In the future, these promise to have an important impact on cancer diagnosis and patient treatment.

ProstaScint scan may enhance identification of prostate cancer recurrences after prostatectomy, radiation, or hormone therapy: analysis of 136 scans of 100 patients.

BACKGROUND: Primary extraprostatic spread or failure after prostate cancer treatment can occur locally in the prostatic fossa and/or metastasize to regional and/or distant lymphatics and/or in bone. We evaluated the ability of the ProstaScint (Cytogen Corp., Princeton, NJ) scan to identify soft tissue recurrence of prostate cancer in patients who failed primary treatment, and we monitored their responses to a secondary treatment. METHODS: The 111indium-labeled monoclonal antibody (ProstaScint) was evaluated in a series of 136 consecutive scans associated with a complete set of relevant clinical and biochemical data. These scans represented 100 patients, imaged between November 1994-May 1998, who underwent a definitive prostate cancer treatment followed by evidence of recurrence. All patients had serum prostate-specific antigen (PSA), Western-blot serum prostate-specific membrane antigen (PSMA), and bone scans. Prostatic fossa and/or lymph node biopsies were available in 33 patients. RESULTS: Overall, no adverse reactions were related to any of the radioactive antibody infusions. The average age was 69 years (range, 48-89 years), serum PSA was 55.9 ng/ml (range, 0-2,185 ng/ml), and serum PSMA was 0.32 (relative intensity levels range, 0.04-0.55). The initial therapies given were radical prostatectomy (55 scans), prostate radiation (74 scans), and/or hormonal therapy (77 scans). Twelve patients exhibited a negative scan. Local recurrence alone was identified in 58 scans (42.6%). Lymph node metastases were identified in 66 scans (48.5%). Of these, 21 had regional metastases alone, and 45 had distant lymph node metastases. Ten scans showed skip lymph node metastases without regional failure. PSA significantly correlated with negative, pelvic, and extrapelvic scan findings (P < or = 0.02). PSMA correlated best with pelvic recurrence and extrapelvic metastases in prostatectomized patients. Thirty-four patients had repeated scans for monitoring treatment response. Of these patients, 19 (56%) showed progression on the second scan, consistent with persistent increase in PSA and PSMA levels in all but 2 patients. Another 11 patients showed no change, and 4 patients showed partial remission, suggesting a response to the salvage treatment. All 20 positive prostate biopsies and 4 of the 7 positive lymph node biopsies correlated with ProstaScint findings, whereas 4 of the 6 patients with a negative biopsy had negative scans (i.e., 89% sensitivity and 67% specificity). Bone metastases were identified in 42 bone scans; 45% of these showed no lymph node metastasis on ProstaScint. In another 24 patients (57%), bone metastases were detected on ProstaScint examinations.

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma.

BACKGROUND: The authors report observed 10-year brachytherapy results in the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. METHODS: One hundred and fifty-two consecutive patients with T1-T3, low to high Gleason grade, prostate carcinoma were treated between January 1987 and June 1988 at Northwest Hospital in Seattle, Washington. Their median age was 70 years (range, 53-92 years). Of these 152 patients, 98 (64%) received an iodine-125 implant alone (Group 1), and the remaining 54 patients (36%), who were judged to have a higher risk of extraprostatic extension, also were treated with 45 gray (Gy) of external beam irradiation to the pelvis (Group 2). No patient underwent lymph node sampling, and none received androgen ablation therapy. Multivariate regression and the Mann-Whitney rank sum test were used for statistical analysis. Preoperative patient data with associated success or failure outcomes at 10 years after treatment were used for training and validating a back-propagation neural network prediction program. RESULTS: The average preoperative prostate specific antigen (PSA) value, clinical stage, and Gleason grade were 11.0 ng/mL, T2, and 5, respectively. The median posttreatment follow-up was 119 months (range, 3-134 months). Overall survival 10 years after treatment was 65%. At last follow-up only 3 of the 152 patients (2%) had died of prostate carcinoma. Ninety-seven patients (64%) remained clinically and biochemically free of disease at 10 years of follow-up and had an average PSA value of 0.18 ng/mL (range, 0.01-0.5 ng/mL). In these patients a period of 42 months was required to reach the average PSA (0.5 ng/mL). The median to last PSA follow-up was 95 months (range, 3-134 months). Postoperative needle biopsies were negative in 56% of patients, positive in 15% of patients, and not available in 29% of patients. Only 6% of patients developed bone metastasis. At 10 years there was no statistically significant difference in treatment outcome between patients who received iodine-125 alone, and those who received iodine-125 with 45-Gy external beam irradiation (P = 0.08). Nevertheless, in these two groups preoperative PSA, stage, and Gleason grade were significantly different (P < 0.01). In the artificial neural network analysis, pretreatment serum PSA was the most accurate predictor of disease-free survival. CONCLUSIONS: Percutaneous prostate brachytherapy is a valid and efficient option for treating patients with clinically organ-confined, low to high Gleason grade, prostate carcinoma. Observed 10-year follow-up documents serum PSA levels superior to those reported in several published external beam irradiation series, and comparable to those published in a number of published radical prostatectomy series.

Method for identifying prostate cells in semen using flow cytometry.

BACKGROUND: Prostate-specific antigen (PSA) cannot differentiate benign prostatic hyperplasia (BPH), from prostatitis, or prostate cancer in the range of 4.0-10 ng/ml. An accurate cytologic or histologic assessment is necessary to confirm the proper diagnosis. The nature of a biopsy tends to make it a selective test not frequently repeated. We are reporting a technique employing semen as a source for the differential diagnosis of prostate epithelial cells. METHODS: Eleven vasectomized and nonvasectomized prostate cancer patients provided semen samples (stage T1 to T2). Two patients provided repeat samples. In addition, 15 vasectomized or nonvasectomized individuals without evidence of disease provided semen samples. Three million cells fixed with 50% ethanol were stained by an antibody (7E11.C5) to prostate-specific membrane antigen (PSMA), Hybritech Antibody (399) to PSA, and cytokeratin 8 and 18. In addition to the antibodies described, a DNA stain To-Pro 3 was used to identify 2n-4n DNA containing cells. A dual laser, Becton Dickinson FACSCaliber cytometer, was used to analyze the samples. RESULTS: All semen specimens contained diploid, cytokeratin 18-positive epithelial cells regardless of disease status. A clear difference between prostate cancer and normal prostate cell samples was observed using staining with 7E11.C5. The ratio of prostatic cells in the total epithelial cell population (PSMA:cytokeratin ratios) was calculated for each specimen. A retrospective study of sixteen semen samples from 11 prostate cancer patients had a mean PSMA:cytokeratin ratio of 0.57, whereas the samples from 15 patients without evidence of cancer had a mean PSMA:cytokeratin ratio of 0.11. This difference was significant. PSA staining was variable and inconsistent. CONCLUSIONS: This report demonstrates that human semen contains prostate cells that can be characterized and used in the clinical diagnosis of prostate cancer.

Impalpable invisible stage T1c prostate cancer: characteristics and clinical relevance in 100 radical prostatectomy specimens--a different view.

PURPOSE: We analyzed 100 consecutive radical prostatectomy specimens to evaluate the extent and clinical relevance of the stage T1c cancers discovered. MATERIALS AND METHODS: All cases were diagnosed by systematic prostatic puncture biopsies because of abnormal prostate specific antigen (PSA) or PSA density. Surgical specimens were examined with the whole organ multiple step-section technique (4 mm.) to identify primary tumor location (peripheral or transition zone cancer), tumor volume, tumor volume divided by prostate volume (percent tumor volume), Gleason score, pathological T stage and positive surgical margins. Tumors smaller than 0.5 cm.3 and without unfavorable pathology (Gleason score 7 or more, or positive surgical margins) were considered insignificant. RESULTS: Median patient age, PSA, tumor volume and Gleason score were 64 years, 8.8 micrograms./l., 1.6 cm.3 and 6, respectively. Of the specimens 46 (46%) had transition zone cancer that was clinically undetectable due to anterior location, while peripheral zone cancers were small, diffuse, anterolateral or in large glands with low percent tumor volume. Transition zone cancer showed greater PSA, PSA density, tumor volume and percent tumor volume than peripheral zone cancer (p = 0.08, 0.03, 0.0002 and 0.0004, respectively), yet with similar Gleason score (p = 0.4). Of the tumors 34 (34%) were locally advanced (stage pT3 and/or positive surgical margins, mostly anterior in 16 transition zone cancers, and apical or posterolateral in 18 peripheral zone cancers), whereas 22 were insignificant (6 transition and 16 peripheral zone cancers). Prostatic puncture biopsies with a core cancer length of less than 3 mm. could have predicted 18 of 19 insignificant tumors but underestimated 13 (33%) and 6 (17%) significant transition and peripheral zone cancers. CONCLUSIONS: The majority of our stage T1c tumors were significant with a distinguished high incidence of transition zone cancer. Therefore, they were large but occult. Transition zone cancer behaved differently than peripheral zone cancer, and warranted considerations during treatment of stage T1c prostate carcinoma.

Free-to-total prostate specific antigen ratio as a single test for detection of significant stage T1c prostate cancer.

PURPOSE: We investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels. MATERIALS AND METHODS: The specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77% underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens. RESULTS: Benign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-toal PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84% of stage T1c cancers were significant and comparable to stage T2 or greater cancers. CONCLUSIONS: Free-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.

Detection of prostate specific antigen in pancreas and salivary glands: a potential impact on prostate cancer overestimation.

PURPOSE: We explored the immunohistochemical expression of prostate specific antigen (PSA) in pancreas and salivary glands. MATERIALS AND METHODS: We investigated 62 specimens from male and female subjects, representing normal cases and several pathological conditions of pancreas and salivary glands. Two commercially available monoclonal antisera for PSA and 1 for prostatic acid phosphatase were used. RESULTS: A consistently positive reaction for PSA and prostatic acid phosphatase, independent of patient sex, was noted in ductal cells of normal pancreas and normal salivary glands, as well as pleomorphic adenoma, adenocarcinoma and all oncocytic epithelial cells of Warthin's tumor. Reaction was absent in normal stromal and acinar cells, and squamous carcinoma. CONCLUSIONS: PSA is detectable in normal and cancer tissues far from the prostate. Therefore, we may not entirely rely on specificity of PSA alone to diagnose metastatic prostate cancer.

Serum tissue polypeptide antigen (TPA) as tumor marker for bladder cancer.

Tissue polypeptide antigen is a differentiation and proliferation marker of non-squamous epithelium and derived neoplasms. No reliable tumor markers are available for bladder cancer. The value of tissue polypeptide antigen was therefore prospectively investigated. The serum tissue polypeptide antigen samples were obtained from 144 newly diagnosed transitional cell carcinoma patients and from 92 patients that were followed after treatment. The normal cut off value was defined at 95 units per liter. Nearly all TaT1 patients had normal TPA values, and 80% of the muscle invasive cancers had normal TPA levels. In those patients where TPA was elevated before treatment its monitoring proved to be a reliable predictor of tumor progression. Tissue polypeptide antigen is a useful marker not for the early detection of bladder cancer but for the monitoring of the efficacy of a treatment.

del(1)(q12) in adenocarcinomas of the prostate.

A structural change of chromosome 1 in q12 may be a new, possibly consistent, chromosome change in adenocarcinoma of the prostate.

Neoadjuvant hormonal therapy before radical prostatectomy decreases the number of positive surgical margins in stage T2 prostate cancer: interim results of a prospective randomized trial. The Belgian Uro-Oncological Study Group.

PURPOSE: We investigated the effect of neoadjuvant treatment before radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 130 patients with stages T2b and T3 prostate cancer was randomized in a multicenter study: 62 underwent immediate radical prostatectomy and 65 received 560 mg. estramustine phosphate daily for 6 weeks preoperatively. RESULTS: For clinical stage T2b tumors the neoadjuvant treatment resulted in a significant decrease in positive surgical margins compared to the nonpretreated group. This difference was not found for clinical stage T3 tumors. The impact on progression and survival still must be analyzed. CONCLUSIONS: Neoadjuvant treatment can be beneficial for clinical stage T2 prostate cancer. Optimal treatment for stage T3 tumors remains controversial.

Morphologic and immunohistochemical changes in prostate cancer after preoperative hormonal therapy. A comparative study of radical prostatectomies.

BACKGROUND: Estramustine phosphate (EMP) and flutamide (FL) were used as reversible preoperative hormonal drugs in the surgical treatment of patients with localized prostate cancer. METHODS: The authors descriptive and quantitatively examined the morphologic and immunohistochemical changes in 40 of 200 step-sectioned radical prostatectomies, obtained after treatment with EMP (25 patients) and with FL (15 patients). Of these, 28 pretreatment needlecore biopsies were available. RESULTS: Every specimen contained adenocarcinoma. Understaging was found in 50% of the cases and a higher Gleason score in 70%. Benign glands underwent atrophy and squamous metaplasia. Treated tumors showed cytoplasmic vacuolization, nuclear pyknosis, fibrosis and lymphocytic infiltrates. The EMP group had an 84% (P < 0.05) higher mean total regression score than the FL group. Estramustine phosphate induced a 56% (P < 0.05) and a 34% decrease in tumoral prostate specific antigen and prostate specific acid phosphatase intensity scores, respectively, versus 29% and 32% after FL. The mean proliferating cell nuclear antigen (PCNA) labeling index and the mean mitotic index of the EMP group were 52% (P < 0.05) and 70% (P < 0.05) lower than those measured in the FL group. Each FL-treated tumor and 92% of EMP-treated tumors expressed chromogranin A (ChrA); ChrA labeling correlated significantly with PCNA labeling. Seventy-six percent of EMP-treated specimens revealed venous thrombosis. CONCLUSIONS: Estramustine phosphate induces important morphologic and immunohistochemical changes in prostate cancer with an apparent decrease of secretory and proliferative activity when compared with FL-treated tumors. These changes represent pitfalls in the diagnosis and grading of treated carcinomas. Nearly every treated adenocarcinoma of the prostate has neuroendocrine differentiation, showing increasing ChrA labeling with higher tumor stage. A significant correlation between tumor proliferation and neuroendocrine differentiation was noticed in this small cohort of patients. There was a high incidence of periprostatic venous thrombosis after EMP treatment.