[Comparative study of surgical efficacy in open versus laparoscopic prostatectomy: virtual prostate reconstruction and periprostatic tissue quantification]. / Estudio comparativo de la eficacia quirúrgica en la prostatectomía abierta y laparoscópica: reconstrucción virtual de la próstata y cuantificación del tejido periprostático.

INTRODUCTION: The introduction of laparoscopic surgery as a procedure to perform radical prostatectomy needs an objective method to evaluate the suitability of this new surgical procedure. The traditional parameters, including the incidence of positive surgical margins, are useful, but not sufficiently objective. Different authors publish different criteria to define positive surgical margins. In addition, there are some technical problems that may ocur during the processing of the surgical specimen by the pathologist, which can give false positive margins. We have used a computer modeling software in connection to scanned images from serial sections of the whole gland, to determine the percentage of extracapsular tissue that surrounds the prostate glands, removed by both, open retropubic and laparoscopic procedures. This percentage can be considered as an objective parameter which can potentially predict the benefit of surgery in predicting cancer control, as well as the clinical success of the surgical procedure. The correlation with the clinical results in the long term--survival and bioche--mical recurrence--will be useful to validate as a last resort the clinical utility of this parameter in the coming years. MATERIALS AND METHODS: We had a total of 32 prostate surgical specimens, 15 from patients who underwent open retropubic prostatectomy and 17 from patients who underwent laparoscopic prostatectomy for this study. After surgery and 24 hours formol fixation, serial cuts were taken at 5 mm thickness intervals to make complete sections ("whole mount") of the prostate. An expert uropathologist reviewed all the surgical sections and drew in each tissue cut the prostatic capsule and tumor contours. The serial images of the whole gland and surrounding prostate tissue were scanned to produce digital images, using a computer software to create a file with capsule information and a file with information on the surrounding fibroadipose tissue (extraprostatic). These procedures allowed the reconstruction of a three dimensional tissue model of the prostatic capsule and the surrounding extraprostatic tissue. Two separate point clouds files were generated, with the purpose of representing capsule and extraprostatic tissue models and software algorithms were used to generate differences in point clouds and thereby quantifying the extracapsular tissue coverage dimension, a parameter that we considered indicative of the adequeacy and feasibility of the surgical procedure. RESULTS: The global percentage of prostate gland surface covered by extracapsular fibroadipose tissue was statistically higher in specimens removed by a laparoscopic procedure when compared to the open retropubic procedure. When a segmental analysis of the gland percentage of coverage was evaluated, it was found this percentage was significantly higher in the apical and inferolateral segments of those glands removed without nerves preservation and in the apical segments of those glands removed with nerves preservation for the laparoscopic prostatectomy. CONCLUSIONS: In our series. laparoscopic prostatectomy contributed superior extracapsular tissue coverage than retropubic prostatectomy. Similarly laparoscopic prostatectomy produced a superior tissue coverage in inferolateral and apical regions on those glands removed without nerve preservation and in the apical regions of those glands removed with nerve preservation. Therefore, the surgical suitability of this technique, when compared to the retropubic, seems to be higher

Monoclonal antibody PD41 recognizes an antigen restricted to prostate adenocarcinomas.

A monoclonal antibody (MAb) designated PD41 (IgG1k) was generated by hyperimmunizing BALB/c mice with a membrane preparation prepared from a moderately to poorly differentiated prostate carcinoma surgical specimen. The immunohistochemical reactivity of MAb PD41 was shown to be highly restricted to the ductal epithelia and secretions of prostate adenocarcinoma tissues. Sixty-five % of the prostate tumor specimens were stained with MAb PD41, whereas no staining of the fetal or benign prostate specimens was observed. PD41 reacted minimally with normal prostate tissues, with less than 1% of the epithelial cells staining. This MAb did not react with nonprostate carcinomas or to a variety of normal human tissues. Using both radioimmunoassay and immunofluorescent procedures, several cultured human tumor cell lines, human blood cells, and purified antigens to prostate-specific antigen and prostatic acid phosphatase also were found not to express the PD41 antigen. MAb PD41 also was shown to bind to the target antigen present in seminal plasma obtained from prostate carcinoma patients but not to seminal plasma from normal donors. Immunoblots of gel-separated components of prostate carcinoma tissue extracts indicate that the molecular weight of the proteins carrying the PD41 antigenic determinant can differ among individual tumors, ranging from Mr 90,000 to greater than 400,000. However, in seminal plasma from prostate cancer patients, the predominant component recognized by PD41 is the diffuse Mr greater than 400,000 band. It appears that this monoclonal antibody may recognize a prostate carcinoma-associated mucin-like antigen, which is preferentially expressed on prostate carcinomas, and therefore, may be a useful marker to distinguish benign prostate hyperplasia from prostate carcinoma.

Human prostate tissue antigens defined by murine monoclonal antibodies.

BALB/c mice were hyperimmunized against a membrane preparation derived from a pool of transurethral resection specimens which included three benign prostatic hyperplasia and one prostate adenocarcinoma tissue samples. The activated lymphocytes were fused with the NS-1 mouse myeloma cell line, and supernatants from immunogen-reactive hybridomas were screened for antibody binding activity using a solid-phase radioimmunoassay against the Calu-1 human lung adenocarcinoma cell line and several membrane preparations derived from various normal human tissues. Hybridoma cultures secreting antibodies which did not appear cross-reactive were doubly cloned by limiting dilution and screened against a large panel of membrane preparations derived from normal prostate, benign prostatic hyperplasia, and prostate adenocarcinoma tissues as well as samples obtained from a variety of normal human tissues. The monoclonal antibodies were also evaluated against 24 normal, virally transformed, and malignant human cell lines. Two monoclonal antibodies were isolated which demonstrated a restricted binding activity to prostate antigens and were not widely cross-reactive with nonprostate normal tissues or cell lines. These antibodies were designated TURP-27 (IgG3, k) and TURP-73 (IgG2a, k). Both of these monoclonal antibodies were reactive against formalin-fixed, paraffin-embedded tissues in the immunoperoxidase assay and were subsequently tested against a variety of normal, hyperplastic, and malignant human tissues. These studies indicated that TURP-27 may be directed against a new prostate organ-associated marker and that TURP-73 is directed against an antigen expressed on prostate and a limited number of other tissues.

Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease.

The lack of a sensitive immunoassay for quantitating serum prostate-specific membrane antigen (PSMA) hinders its clinical utility as a diagnostic/prognostic biomarker. An innovative protein biochip immunoassay was used to quantitate and compare serum PSMA levels in healthy men and patients with either benign or malignant prostate disease. PSMA was captured from serum by anti-PSMA antibody bound to ProteinChip arrays, the captured PSMA detected by surface-enhanced laser desorption/ionization mass spectrometry, and quantitated by comparing the mass signal integrals to a standard curve established using purified recombinant PSMA. The average serum PSMA value for prostate cancer (623.1 ng/ml) was significantly different (P < 0.001) from that for benign prostate hyperplasia (117.1 ng/ml) and the normal groups (age <50, 272.9 ng/ml; age >50, 359.4 ng/ml). These initial results suggest that serum PSMA may be a more effective biomarker than prostate-specific antigen for differentiating benign from malignant prostate disease and warrants additional evaluation of the surface-enhanced laser desorption/ionization PSMA immunoassay to determine its diagnostic utility.

Flt3-ligand induces transient tumor regression in an ectopic treatment model of major histocompatibility complex-negative prostate cancer.

We assessed the in vivo efficacy of Flt3-ligand (Flt3-L) treatment in C57BL/6 mice bearing a well-established MHC class I-negative prostate carcinoma TRAMP-C1. Flt3-L immunotherapy was initiated approximately 30 days after tumor inoculation, a time when > or =80% of the mice had palpable TRAMP-C1 tumors. Treatment with Flt3-L at 10 microg/day for 21 consecutive days suppressed TRAMP-C1 tumor growth and induced tumor stabilization (P = 0.0337). Enhanced tumor regression was demonstrated at a higher dose of 30 microg/day (P < 0.0001). Tumors excised from mice treated with Flt3-L were smaller than carrier-treated controls and contained a more pronounced mixed inflammatory cell infiltrate primarily composed of mphi. In regressor nice, tumors reappeared at the site of injection when Flt3-L therapy was terminated. When the experiment was repeated with MHC class I-positive TRAMP-C1 cells, tumor stabilization and/or regression was again observed after treatment (P < 0.0001); however, once again, tumors reappeared after the termination of therapy despite an extended treatment schedule (35 days). MHC class I-negative variants were present in tumors isolated from carrier- and Flt3-L-treated mice, and this phenotype could be reversed by IFN-gamma treatment in vitro. Thus, Flt3-L treatment of mice with preexisting transplantable prostate tumors results in tumor regression that is dose-dependent and accompanied by a pronounced mixed-cell inflammatory tumor infiltrate. However, disease relapse was invariably observed after the termination of therapy, which suggests that Flt3-L treatment of advanced MHC- prostate cancers will require adjuvant modalities to achieve a durable response.

Immunohistochemical localization of prostate carcinoma-associated antigens.

The immunoperoxidase technique was used to study the localization and distribution of antigens reactive with two monoclonal antibodies, D83.21 and P6.2, produced against cultured prostate tumor cells, in formalin-fixed, paraffin-embedded histological sections of human tissues. Monoclonal D83.21 reacted with 11 of 19 (58%) primary prostate carcinomas and 1 of 6 (17%) metastatic tumors, whereas monoclonal P6.2 reacted with 14 of 19 (68%) primary and 4 of 6 (67%) metastatic prostate tumors. Neither antibody reacted with five primary prostate tumors and one metastatic prostate tumor. In some tumor cells, the antigens recognized by these monoclonals were localized in either the cytoplasm or cell membrane, while in other tumor cells, both diffuse cytoplasmic and membrane or focal staining patterns were observed. In addition to the variable staining patterns, antigenic heterogeneity was also noted within most prostate tumors examined. Two types of staining variability were observed: (a) tumor cells in one area of the tissue section stained positive, but in another area they did not react with the antibody; and (b) both stained and unstained tumor cells were adjacent to each other. These results would suggest that a panel of monoclonals will be required to detect the different subpopulations of prostate tumor cells. Neither antibody reacted with 6 normal or 12 benign prostate tissues, nor any of a variety of other normal human tissues except for staining of the proximal tubules of normal kidneys. The antigen detected by P6.2 demonstrated a wider tissue distribution being found on bladder, breast, lung, and pancreatic tumors, whereas the antigen recognized by D83.21 was restricted to prostate and bladder carcinomas. These antibodies may have clinical applicability for the identification of prostate tumor cells in biopsy specimens and for immunohistopathological classification of prostate carcinomas.

Monoclonal antibodies to human prostate and bladder tumor-associated antigens.

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays. A hybridoma clone (83.21) was isolated that secreted antibodies which preferentially bound to several prostate and bladder cancer cell lines but did not bind to a variety of other normal and malignant human cell lines. This antibody also reacted with a cytomegalovirus-transformed human embryonic lung cell line but not to normal human embryonic lung cells. Quantitative adsorption studies demonstrated that the 83.21 monoclonal antibody was strongly reactive to membrane preparations from human prostate adenocarcinoma tissue and a liver metastasis of prostate carcinoma. Little or no binding activity was observed against two other prostate carcinomas, bening prostatic hyperplasia, normal prostate, or normal liver. Binding studies indicate that the 83.21 monoclonal antibody does not bind to alpha-fetoprotein, carcinoembryonic antigen, prostatic acid phosphatase, human leukocyte antigen, beta 2-microglobulin, HLA-Dr antigens, fibronectin, or prostate antigen. The data indicate that we have isolated a monoclonal antibody that binds to an antigen(s) expressed by several urogenital carcinoma cell lines as well as human prostate tumor tissue and that the antibody is not directed against well-known human tumor cell markers.

Consensus statements on radiation therapy of prostate cancer: guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy. American Society for Therapeutic Radiology and Oncology Consensus Panel.

PURPOSE: To develop evidence-based guidelines for (1) prostate re-biopsy after radiation and (2) radiation therapy with rising prostate-specific antigen (PSA) levels after radical prostatectomy in the management of patients with localized prostatic cancer. DESIGN: The American Society of Therapeutic Radiology and Oncology (ASTRO) challenged a multidisciplinary consensus panel to address consensus on specific issues in each of the two topics. Four well-analyzed patient data sets were presented for review and questioning by the panel. The panel sought criteria that would be valid for patients in standard clinical practice as well as for patients enrolled in clinical trials. Subsequent to an executive session that followed these presentations, the panel presented its consensus guidelines. RESULTS AND CONCLUSIONS: Based on the data presented, the prostate re-biopsy negative rates ranged from 62% to 80% for patients with stage T1-2 tumors. The panel judged that prostate re-biopsy is not necessary as standard follow-up care and that the absence of a rising PSA level after radiation therapy is the most rigorous end point of total tumor eradication. Further, the panel judged that re-biopsy may be an important research tool. Based on the data presented, the long-term (5 years or more) PSA remission rate after salvage radiation therapy ranges from 27% to 45%. The panel requested results from prospective randomized trials to evaluate optimally this information. The panel judged that the total dose of radiation should be 64 Gy or slightly higher and that, in patients with or without radiation therapy, there is no standard role for androgen suppressant therapy for rising PSA values after prostatectomy.

Prostate-specific membrane antigen levels in sera from healthy men and patients with benign prostate hyperplasia or prostate cancer.

Prostate-specific membrane antigen (PSMA) serum levels have been proposed to be of prognostic significance in patients with advanced prostate disease. The objective of the present study was to confirm PSMA serum expression by Western blot techniques, to determine whether such data could assist in the differentiation of benign from malignant prostatic disease, and to determine the suitability of serum PSMA measurements in predicting recurrent or progressive prostate malignancies. We measured PSMA, a transmembrane glycoprotein identified in prostate epithelial cells, in the sera of 236 normal individuals and cancer patients by Western blot analysis. Within the normal male population, PSMA levels increase with age and were found to be significantly elevated in subjects more than 50 years of age when compared to those of younger men. We did not confirm previous reports that serum PSMA measurements could distinguish late-stage prostate carcinoma from early-stage prostate carcinoma, nor did we find PSMA to be more effective than prostate-specific antigen in monitoring prostate cancer patient prognosis. Furthermore, we found elevated serum PSMA in healthy females, and, similar to the healthy male population, the levels increased with age, with the highest levels found in the sera from breast cancer patients. These latter observations further support that PSMA is not a specific biomarker for prostate cancer and that a variety of normal and diseased tissue may contribute to the serum levels of PSMA.

PSA for outcome prediction and posttreatment evaluation following radiation for prostate cancer: do we know how to use it?

Pretreatment prostate-specific antigen (PSA) has been shown to be a powerful predictor of expected outcome after radiation for prostate cancer. Additional measures such as recursive partitioning analysis and PSA Cancer Volume calculations are further refining this useful tool to provide the greatest degree of prognostic information. The post-treatment PSA level is also being used as a means to assess therapeutic efficacy rapidly and objectively. Although no single PSA value has been shown to equate to long-term clinical tumor control consistently, consensus has been reached regarding the value of a rising PSA level as an early surrogate for tumor recurrence. Since the first introduction of PSA as a tumor marker, we have become much more comfortable with what it means, the ways it can help us, and how to use it.

The effect of TURP on prognosis in prostatic carcinoma.

Of 553 patients definitively irradiated for biopsy proven prostatic adenocarcinoma from January 1976 to March 1986, 287 patients with a minimum follow-up of 4 years were studied. One hundred sixty-two patients had transurethral prostatic resection (TURP); one hundred twenty-five patients did not. When subdivided by stage and histologic grade, those patients with poorly differentiated tumors who underwent TURP had a noticeably higher, but not statistically different, incidence of bony metastasis as compared to those who did not have TURP. Survival at 5 years also appeared to be better in patients with poorly differentiated and stage C disease without TURP. However, local tumor recurrence in poorly differentiated tumor with TURP was 42% as compared to 20% in the NO TURP group, p = .04. Moreover, when the incidence of osseous metastasis was assessed by local tumor status, 20% of the TURP patients with local tumor control developed metastases as compared to 66% of those with local failure. Similarly, within the NO TURP group, the incidence of bony metastasis was 16% for those with local control and 50% for those with local recurrence, p = .005 in both cases. Survival was likewise affected by local tumor control, regardless of whether or not TURP was performed. In patients with local tumor control, survival was 80% at 5 years with TURP and 86% without TURP (p greater than 0.1). In contrast, only 14% of patients with local recurrence and TURP were alive at 5 years which was not statistically different from the 32% survival in those with local recurrence but NO TURP. It seems, therefore, that comparing prognosis by TURP alone overlooks the inherent characteristics of the tumor and the extent of the disease.

The effect of prior transurethral resection of the prostate on post radiation urethral strictures and bladder neck contractures.

Patients treated for prostate cancer from 1975-1982 were reviewed to assess if pre-irradiation transurethral resection of the prostate (TURP) predisposed to the formation of post treatment urethral strictures or bladder neck contractures. A total of 368 patients were treated with external beam irradiation delivered by a linear accelerator or 125I interstitial implants. Of the 253 patients treated by external beam, 138 patients had a history of at least one TURP before treatment. Implants were performed in 115 patients and 57 had a history of TURP before treatment. A total of 40 patients from both groups developed post treatment complications of urethral strictures or bladder neck contractures. Three patients developed both complications. An analysis of the 40 patients revealed that 29 (72.5%) patients had a TURP performed within a median time of 33 days prior to their initiation of radiation therapy. Of 195 patients in the prior TURP group, 29 (15%) developed one or both complications. Only 11 (6%) of the 173 patients in the non-TURP group developed one or both complications. This comparison was statistically significant with a p value of .025. Various factors analyzed including the treatment regimen, histologic grade, stage of disease, and volume of prostatic tissue removed at surgery did not show any positive correlation. Multiple TURP's were evaluated for greater distribution to the incidence of post treatment complications. The prior TURP group of 195 patients contained 60 with a history of at least two TURPs before radiation therapy. Eleven (18.3%) developed one or both complications. Of the 135 patients in the single TURP group, 18 (13.3%) developed complications. This was not statistically significant. Therefore, we concluded that the initial TURP was its mechanical description of mucosa and resultant scarring is a predisposing risk for development of urethral strictures or bladder neck contractures. Review of the literature concerning time sequence for healing of the urethra shows 4-6 weeks to be appropriate interval between surgery and radiation.

Prostate-specific antigen for pretreatment prediction and posttreatment evaluation of outcome after definitive irradiation for prostate cancer.

PURPOSE: This study was undertaken to assess the predictive value of pretreatment prostate-specific antigen (PSA) and the difference between clinical and PSA disease-free status in patients with long-term follow-up after irradiation for prostatic carcinoma. Comparison of the distribution of prognostic factors between surgical and radiation series was also made. METHODS AND MATERIALS: From 1975-1989, 652 patients with clinical Stage A2-C prostatic adenocarcinoma were definitively irradiated using external beam therapy. One hundred and fifty patients with banked serum and up to 14 years follow-up have pretreatment PSA levels and 355 patients with up to 17 years follow-up have posttreatment values. Treatment failure was analyzed by tumor stage, grade, and four pretreatment PSA categories. Disease-progression was evaluated by clinical and biochemical (PSA) endpoints. Prognostic factors were compared to two surgical series. RESULTS: A significant difference was seen in clinical and PSA disease-free (PSA < or = 4.0 ng/ml) status based on tumor grade, stage, and pretreatment PSA category. Although the expected clinical outcome has been well-documented previously, results based on posttreatment PSA levels show 5-year disease-free survivals reduced by 10-16% and 10-year survivals lessened by 15-39% depending upon the particular tumor grade and stage. The earlier stage, lower grade tumors showed the largest difference between clinical and biochemical recurrence rates at the longest interval from treatment. Even more notable were the differences in the clinical and PSA disease-free rates based on the pretreatment PSA level. Comparing the irradiated patients to two surgical series showed that the former had a larger percentage of more advanced stage tumors with more unfavorable PSA levels as compared to prostatectomy patients. CONCLUSION: With long-term follow-up, the pretreatment PSA level continues to be a powerful predictor of clinical and biochemical outcome in patients irradiated for apparently localized prostate cancer. Differences between clinical and PSA outcome can be considerable, but oftentimes clinically insignificant. The distribution of prognostic factors between radiation and prostatectomy series seems to favor the latter.

Triple course external beam radiotherapy for carcinoma of the prostate.

In 1976 we began using a triple-course technique of external beam irradiation for localized carcinoma of the prostate. The treatment consisted of 2 courses of 20 Gy in 2 weeks to the pelvis and a third course of 20-25 Gy in 2-2 1/2 weeks as a boost to the prostate. A 2 week rest followed the first and second courses. The results of this treatment technique are reported on the first 50 patients who had been followed for at least 3 years. Although 96% of these patients developed bladder and/or bowel reactions, the majority of the symptoms were in the very mild to mild category, with only 2% severe reactions referrable to each organ. The incidence of late complications in this series compared favorably to those reported by other authors. Clinical local control was 96% while post-treatment needle biopsy performed on 22/50 patients yielded a negative rate of 86%. Those with Stages A and B disease had a negative biopsy rate of 94%. Three-year uncorrected disease-free survival for the whole group was 54%. This study has shown that with triple course external beam irradiation, excellent control of localized carcinoma of the prostate can be achieved with minimal acute morbidity.

Urethral cytology following cystectomy for bladder carcinoma.

There is a high probability of urethral carcinoma in patients who have had cystectomy for carcinoma of the urinary bladder, and their survival is poor when the disease is sufficiently advanced to be symptomatic or tumor is visible endoscopically. This study was undertaken to evaluate urethral cytology as a means of detecting and diagnosing in situ and invasive carcinoma of the urethral remnant following cystectomy. A total of 109 cytology specimens were examined from 65 patients who had cystectomy for bladder cancer. "Positive" or "suspicious" cytologic diagnoses of cancer were made on 28 patients; 24 had urethrectomy and 11 proved to have invasive carcinoma, 10 had carcinoma in situ and three had atypia or metaplastic changes in the urethra. One of 37 patients with "negative" cytologic diagnoses was found to have a low-grade carcinoma. It is suggested that all patients who undergo cystectomy without urethrectomy be followed with urethral cytological examination at regular intervals for an indefinite period.

Overexpression of p53 in prostate carcinoma is associated with improved overall survival but not predictive of response to radiotherapy.

p53 gene mutations are among the most common specific genetic alterations in human cancer. Inactivation of p53 and subsequent protein accumulation has been implicated in a variety of human malignancies and associated with prostate cancer progression. In this study, we assessed p53 protein overexpression and gene mutations in prostate carcinoma and investigated associations between p53 alterations and clinicopathological parameters, survival, and response to radiotherapy. We evaluated 58 archival formalin-fixed, paraffin-embedded prostate carcinomas to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. p53 mutational status of tumor DNA was evaluated using polymerase chain reaction-single-strand conformation polymorphism analysis of exons 5-9 and confirmed by direct DNA sequencing. Univariate and multivariate statistical analysis was used to determine the association of p53 status with clinical characteristics and response to radiotherapy. Overexpression of p53 was detected in 42 (72%) of 58 primary prostate carcinomas, but was undetectable in 7 samples of benign prostatic hyperplasias or 5 samples of normal prostate tissue. p53 exon 5-9 mutations were detected in 8 (14%) of 58 patient specimens. p53 mutational status, but not overexpression, was associated with higher Gleason scores (p=0.0145). Neither p53 overexpression nor mutation was associated with clinical stage, biochemical disease-free probability, or predictive of response to radiotherapy. p53 protein accumulation was inversely associated with improved overall survival (p=0.0108). Our studies demonstrate that p53 protein accumulation is a frequent alteration in prostate cancer. The disparity between p53 protein overexpression and p53 exon 5-9 mutations suggests the possibility of mutations outside this region or stabilization of wild-type p53 by alternative mechanisms. In our patient population, p53 protein overexpression or mutational status was not predictive of outcome in patients treated with radiation therapy. Additional studies are needed to further evaluate the association between p53 protein overexpression and improved overall survival.

Analysis of prostatic tumor cultures using fluorescence in-situ hybridization (FISH).

Analysis of ten primary prostatic tumor cultures using fluorescence in-situ hybridization (FISH) with pericentromeric probes for chromosomes 7, 8, 10, 16, 17, and 18 revealed aneusomies in nine of these specimens. Classical cytogenetics by G-banding indicated that only four of those same ten specimens had any (but not consistent) clonal abnormalities. This preliminary study suggests that aneusomy is a common event in early-stage prostatic tumors, and also supports the notion that multiple chromosomes are involved. In combination with routine cytogenetic analysis, FISH is thus likely to be a powerful tool in the evaluation of prostatic cancer.

Cytogenetic analysis of four primary prostatic cultures.

Primary cell cultures were established from tissue specimens obtained from patients undergoing transurethral resection of the prostate. Cytogenetic analysis of these cultures revealed a normal male chromosomal complement from one and a 45,X karyotype from another patient with benign prostatic hyperplasia. In addition, a normal male chromosomal complement was observed from a moderately differentiated prostatic carcinoma, and a grossly abnormal karyotype was observed from a poorly differentiated adenocarcinoma of the prostate. This latter specimen contained a modal chromosome number of 84 with several consistent marker chromosomes including homogeneous staining regions and double minutes, and no normal chromosomes 3, 5, 10, 15 or Y. Primary prostatic cell cultures exhibit epithelial-specific keratin intermediate filament proteins, and, in conjunction with cytogenetic analysis, provide a model for the study of human prostate cancer.

Cytogenetic evaluation of 20 cultured primary prostatic tumors.

We report the cytogenetic evaluation of 20 cultured cell strains derived from primary prostatic adenocarcinomas obtained from radical prostatectomies. The majority of the strains contained cells with only normal male karyotypes (46,XY), but cytogenetically abnormal clonal populations were found in five strains. Two of those strains contained aberrations involving the Y chromosome, one with a -Y and one with a +Y. Three strains (one of which also had the XYY karyotype) exhibited cells with double-minute chromosomes and four strains contained near tetraploid cells.

Radical prostatectomy. Patterns of local failure and survival in 67 patients.

Sixty-seven patients with localized carcinoma of the prostate were treated by radical prostatectomy unaided by adjunctive hormonal therapy. Seven patients (10%) have been lost to follow-up, and 13 patients (19%) have died of other causes without evidence of prostate cancer. The crude or direct survival free of disease for traced patients with clinical Stage B1 nodules (11) and clinical B2 lesions (20) followed for at least fifteen years is 36 per cent and 25 per cent, respectively; the crude or direct survival free of disease for pathologic B (29) and C (12) tumors followed for fifteen years is 31 per cent and 8 per cent, respectively. The local failure incidence at fifteen years for pathologic Stage B tumors is 17 per cent and for pathologic C tumors 31 per cent. Capsular invasion alone on histologic examination did not increase the rate of local or distant failure above that noted for tumors that were entirely intracapsular. However, seminal vesicle invasion is associated with a 44 per cent local failure and 66 per cent distant failure rate. The interval between radical prostatectomy and first failure averaged sixty-nine months (median 56 months) and with hormonal therapy the interval between first failure and death averaged seventy months (median 62 months). The patients who underwent radical prostatectomy in this series represent 22 per cent of the 318 patients presenting with localized prostate cancer between 1960 and 1974. A 1.5-cm nodule was found in 5.5 per cent of the presenting population, and all but one of these patients were treated by radical prostatectomy.