Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).

BACKGROUND: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. MATERIALS AND METHODS: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. RESULTS: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88-12.56). CONCLUSION: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.

Gene expression, localization, and characterization of endothelin A and B receptors in the human adrenal cortex.

Compelling evidence indicates that the endothelium-derived potent vasoconstrictor endothelin-1 (ET-1) stimulates aldosterone secretion by interacting with specific receptors. Although two different ET-1 receptors have been identified and cloned, the receptor subtype involved in mediating aldosterone secretion is still unknown. Accordingly, we wished to investigate whether the genes of ET-1 and of its receptors A and B are expressed in the normal human adrenal cortex. We designed specific primers for ET-1 and the ETA and ETB receptors genes and developed a reverse transcription polymerase chain reaction (RT-PCR) with chemiluminescent quantitation of the cDNA. In addition, we carried out 125I ET-1 displacement studies with cold ET-1, ET-3 and the specific ETA and ETB ligands BQ123 and sarafotoxin 6C. Localization of each receptor subtype was also investigated by autoradiography. Binding experiments were first individually analyzed by Scatchard and Hofstee plot and then coanalyzed by the nonlinear iterative curve fitting program Ligand. Histologically normal adrenal cortex tissue, obtained from kidney cancer patients (n = 7), and an aldosterone-producing adenoma (APA), which is histogenetically derived from the zona glomerulosa (ZG) cells, were studied. Results showed that the ET-1, ETA and ETB mRNA can be detected by RT-PCR in all adrenal cortices as well as in the APA. The best fitting of the 125I ET-1 displacement binding data was consistently provided by a two-site model both in the normal adrenal cortex (F = 22.1, P < 0.0001) and in the APA (F = 18.4, P < 0.0001). In the former the density (Bmax) of the ETA and ETB subtype was 2.6 +/- 0.5 pmol/mg protein (m +/- SEM) and 1.19 +/- 0.6, respectively. The dissociation constant (Kd) of ET-1, ET-3, S6C, and BQ-123 for each receptor subtype resulted to be within the range reported for human tissue for the ETA and ETB receptors. In the APA tissue the Bmax tended to be lower (1.33 and 0.8 pmol/mg protein, for the ETA and ETB, respectively) but the Kd were similar. Autoradiographic studies confirmed the presence of both receptor subtypes on the ZG as well as on APA cells. Thus, the genes of ET-1 and both its receptor subtypes ETA and ETB are actively transcribed in the human adrenal cortex. Furthermore, both receptor subtypes are translated into proteins in ZG and APA cells.

Duplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours.

Previous karyotyping showed a combined trisomy of chromosome 7 and 17 in sporadic and hereditary papillary renal cell tumours (RCT). A recent molecular analysis revealed a mutation in the MET tyrosine kinase (chromosome 7q31) in the germline of four out of seven families with hereditary papillary RCT (HPRCT). We have analysed germline cells as well as multiple tumours obtained from HPRCT families and sporadic cases for alteration of the MET tyrosine kinase and for allelic duplication at chromosome 7 and 17. We have detected a germ line mutation in the MET tyrosine kinase in one of the two families with HPRCTs and also found the same mutation in the germ line of one patient with clinically recognized multiple, bilateral papillary RCTs but without family history. The mutant MET allele is consequently duplicated and overexpressed in tumour cells indicating that duplication of the mutant MET allele is necessary before cells enter the tumorigenic pathway. The lack of germline mutation in two members of another HPRT family and duplication of the same parental allele of chromosome 7 in multiple tumours suggests that a germ line event other than mutation of MET tyrosine kinase is involved in the development of these tumours. Duplication of different alleles of chromosome 7 in sporadic and of chromosome 17 in both types of tumours excludes a germline mutation at these chromosomal sites.

Pituitary adenylate-cyclase activating peptide enhances aldosterone secretion of human adrenal gland: evidence for an indirect mechanism, probably involving the local release of catecholamines.

Evidence is accumulating that the adrenal medulla exerts a paracrine control on the secretory activity of the cortex by releasing catecholamines and several regulatory peptides. Pituitary adenylate-cyclase activating peptide (PACAP) is contained in the adrenal medulla of several mammalian species and in human pheochromocytomas. Thus, we investigated whether PACAP exerts a modulatory action on steroid secretion by the human adrenal cortex in vitro. Adrenal slices (including both capsule and medulla) and dispersed adrenocortical cells (obtained from the gland tail deprived of medulla) were employed. Both adrenal preparations secreted aldosterone (ALDO) and cortisol in response to 10 nmol/L ACTH. PACAP (10 nmol/L) was found to enhance basal ALDO production by adrenal slices, but not by dispersed cells. PACAP was ineffective on cortisol secretion of both preparations. Adrenal slices displayed a marked ALDO, but not cortisol, secretory response to 100 nmol/L isoprenaline or noradrenaline. l-Alprenolol (1 mumol/L), a specific beta-adrenoceptor antagonist, completely suppressed the ALDO response to both beta-adrenoceptor agonists and 10 nmol/L PACAP, without per se altering basal ALDO output by adrenal slices. PACAP (10 nmol/L) induced a net rise in catecholamine release by adrenal slices. Taken together, our present findings suggest that PACAP indirectly stimulates ALDO secretion by the human adrenal cortex, probably by eliciting the local release of catecholamines by medullary chromaffin cells that are also scattered in the cortical tissue, especially the zona glomerulosa.

Effects of adrenomedullin on the human adrenal glands: an in vitro study.

Numerous lines of evidence indicate that adrenal medulla exerts a paracrine control on the secretory activity of the cortex by releasing catecholamines and several regulatory peptides. Adrenomedullin (ADM) is contained in adrenal medulla of several mammalian species, including humans. Thus, we investigated whether human ADM1-52 exerts a modulatory action on steroid secretion of human adrenal cortex in vitro. Dispersed adrenocortical cells (obtained from the gland tail deprived of chromaffin cells) and adrenal slices (including both capsule and medulla) were employed. ADM specifically inhibited angiotensin II-stimulated aldosterone secretion of dispersed cells and enhanced basal aldosterone production by adrenal slices, minimal effective concentrations being 10(-7) and 10(-9) mol/L, respectively. These effects of ADM were suppressed by the CGRP1 receptor antagonist CGRP8-37 (10(-5) mol/L). Neither basal and ACTH-stimulated aldosterone secretion of dispersed cells nor agonist-enhanced aldosterone production by adrenal slices were affected by ADM, which also did not alter cortisol secretion of both types of adrenal preparations. ADM (10(-6) mol/L) blunted the aldosterone secretagogue action of the Ca2+ ionophore A23187 (10(-5) mol/L) on dispersed cells and adrenal slices. The beta-adrenoceptor antagonist l-alprenolol (10(-6) mol/L) suppressed aldosterone response of adrenal slices to 10(-7) mol/L isoprenaline and ADM. ADM concentration dependently raised epinephrine and norepinephrine release by adrenal slices, minimal effective concentration being 10(-9) mol/L. Collectively, these findings suggest that ADM, acting via the CGRP1 receptor subtype, exerts a direct inhibitory effect on angiotensin II-stimulated aldosterone secretion, which, when the integrity of adrenal tissue is preserved, is overcome and reversed by an indirect stimulatory action, conceivably involving the release of catecholamines by adrenal chromaffin cells.

Cytoskeletal and cytocontractile protein composition of stromal tissue in normal, hyperplastic, and neoplastic human prostate. An immunocytochemical study with monoclonal antibodies.

Monoclonal antibodies specific for protein markers of smooth muscle and nonmuscle cell differentiation were applied to cryosections of normal, hyperplastic, and neoplastic human prostate specimens in order to determine whether differences in the distribution of target antigens could be detected among the various tissues. Immunofluorescence assays showed that vimentin, desmin, smooth-muscle-type alpha-actin, and both smooth muscle and nonmuscle myosin heavy chains do not change their patterns of labeling in the stromas of normal, BPH, and carcinomatous prostates. By contrast, cytokeratin 18, a differentiation marker of simple epithelia, and to a lesser extent cytokeratin 8, was consistently found in stromal tissue of the "transition zone", but only scarcely in the stroma of the "peripheral zone" from normal prostate, and was completely unexpressed in benign hyperplasia. Prostatic carcinoma from the "peripheral zone" expressed this cytoskeletal component only in trace amounts. Moreover, in prostate showing coexistence of hyperplasia and neoplasia (in the "peripheral zone"), the stroma of BPH closely resembled the stroma surrounding the carcinoma; that is, it was completely unreactive with the anti-cytokeratin 18 antibody. Expression of cytokeratins in extraepithelial tissues has been previously correlated with the achievement of a proliferative state, notably in embryogenesis, in tissue regeneration, and in various pathological forms of proliferation and growth, including some tumors of mesenchymal origin. Our results indicate the following: (1) cells in the stromal tissue of normal prostate are of smooth muscle type and are heterogeneous as concerns cytokeratin distribution; (2) we show, for the first time, the existence of a marker that is differentially distributed in the "transition" versus "peripheral" zone; (3) the expression of cytokeratins in the stroma is lost with the development of hyperplasia and only partially recovers with neoplasia; (4) the pattern of stromal tissue, concerning cytokeratin 18 expression, does not change with different BPH locations ("transition" versus "peripheral" zone); and (5) contrary to expectations, cytokeratin 18 expression disappears in conditions presumably involving stromal cell proliferation.

Total PSA, free PSA/total PSA ratio, and molecular PSA detection in prostate cancer: which is clinically effective and when?

OBJECTIVES: To ascertain when the serum determination of the free prostate-specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, and whether the identification of PSA or prostate-specific membrane antigen (PSM) mRNA in circulating cells has diagnostic advantages over the determination of their protein product. METHODS: fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH). mRNA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identified in these samples by means of reverse transcriptase-polymerase chain reaction. RESULTS: Overall, at a fixed specificity of 95%, the sensitivity of tPSA was 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BPH. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with satisfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 38 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. CONCLUSIONS: The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utility of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no clinical interest.

Prostate cancer probability after total PSA and percent free PSA determination.

UNLABELLED: The percent free PSA value is a promising diagnostic tool for prostate cancer. However, its actual role has not yet been established because of the widely diverging sensitivity and specificity values. This could depend at least in part on analytical difficulties, since the free PSA concentration is much lower than that of total PSA. The present investigation was designed to evaluate the diagnostic performance of the percent free PSA in the most favorable analytical conditions. MATERIALS AND METHODS: 81 patients affected by newly diagnosed, untreated primary prostate cancer (CaP) and 239 patients with untreated benign prostatic hyperplasia (BPH) were prospectively enrolled. Hybritech total and free PSA were measured by the same technician using the same reagent batch. RESULTS: The percent free PSA was not significantly associated with age, tumor stage, gland volume, Gleason score, and total PSA, nor was it significantly affected by concomitant prostatic complications either in CaP or BPH. Percent free PSA was more effective than total PSA in the differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. Percent free PSA determination could have reduced the rate of unnecessary biopsies in cases with total PSA > or = 4 ng/mL and > or = 10 ng/mL (avoided biopsies 61% and 63%, respectively). The post-test probability of the disease, which represents the proportion of patients with a positive percent free PSA value who have the disease, was, however, relatively low in younger patients with total PSA within the normal range. CONCLUSIONS: The diagnostic performance of the percent free PSA value is enhanced when the methodological variability is reduced, particularly in men with low total PSA. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 ng/mL. The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL. However, due to its relatively low post-test probability, the percent free PSA value should be interpreted with caution in the decision-making related to individual patients and should be used in association with clinical and instrumental evaluation of the patient.

[Heredity in renal and prostatic neoplasia]. / L'ereditarietà nelle neoplasie renali e prostatiche.

There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of RCC, but some are associated with high risk of pheochromocytoma and low risk of RCC. The VHL gene is evolutionary conserved and encodes for a specific protein (pVHL). VHL protein downregulates transcriptional elongation and so suppresses the expression of proto-oncogenes and growth factors. Recently reintroduction of wild-type, non mutant, VHL gene into VHL deficient RCC cell line 786-O had no demonstrable effect on their in vitro growth but inhibited their ability to form tumors in nude mice. So far, VHL mutations or hypermethylations have been found in 76% of sporadic RCC. On the contrary, up to now, no 3p allele loss or VHL mutations have been detected in pRCC. Preliminary studies in familiar pRCC are pointing on genetic changes on chromosomes 1, 7, 16 and 17. As far as prostate cancer is regarded, men with a family history of prostate cancer have an age dependent, significantly increased PCa risk. For familiar clustering, of PCa the two main factors are early age at onset of the disease and the number of multiple affected family members. Hereditary prostate cancer is a subset of familiar prostate cancer with a pattern of distribution consistent with Mendelian inheritance. Hereditary prostate cancer is clinically defined as a clustering of 3 or more relatives within any nuclear family; or the occurrence of prostate cancer in each of 3 generations in either the probands paternal or maternal lineage; or a cluster of 2 relatives affected within 55 years of age or less. Therefore, hereditary prostate cancer may be seen as a multistep carcinogenesis, and clustering may be explained by Mendelian inheritance of a rare (frequency in population 0.36%) dominant, highly penetrant, allele. The estimated cumulative risk of developing PCa, is 88% for carriers as compared with 5% for non carriers. There are conflicting reports of an associated increased incidence of breast cancer in female relatives of men with familiar prostate cancer. In conclusion, there is a clear associatio

Clinical and pathological characteristics of patients presenting with biochemical progression after radical retropubic prostatectomy for pathologically organ-confined prostate cancer.

INTRODUCTION: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). MATERIALS AND METHODS: Clinical and pathological features of 350 consecutive patients with pathologically OC PCa treated only with RP and bilateral pelvic lymphadenectomy were analyzed, retrospectively, to identify predictor parameters of prostate-specific antigen (PSA) failure (PSA>or=0.4 ng/ml). The median follow-up was 58.6 months (range: 3.9-183 months). All pathological specimens were step sectioned at 4-mm intervals. Kaplan-Meier progression-free survival rates and chi2 test were adopted for statistical analyses. Multivariate Cox proportional hazard regression models were used to test the association between pathological Gleason score and surgical margin status. RESULTS: 67 patients (19.1%) failed at a median follow-up of 40.2 months (range 1.9-123.3). Age and preoperative PSA failed to reveal significance also in patients with serum PSA>or=20 ng/ml (p=0.46). Patients with T3 clinical stage had a higher progression rate compared to T1C and T2 (43.5 vs. 27.8 and 17.3%, respectively) even if no high statistical significance was pointed out. Presence of perineural infiltration (p=0.04) and prostatic apex infiltration (p=0.74) in the prostatectomy specimens failed to reveal significance. A high pathological Gleason score (>or=7; p=0.0003) and surgical margin status (p<0.0001) were shown to be the most powerful predictive parameters of biochemical progression. CONCLUSIONS: In patients with pathologically OC PCa the presence of a high pathological Gleason score and positive surgical margins appear to represent the most important factors for prediction of outcome following RP.

Obstructive primary bladder neck disease: evaluation of the efficacy and safety of alpha1-blockers.

OBJECTIVE: The efficacy and safety of using alpha(1)-adrenergic blockers for treating primary bladder neck obstruction in young and middle-aged men was assessed as the first therapeutic step, before surgery, in a symptomatic non-neurogenic selected group of patients. MATERIALS AND METHODS: From January 1995 to December 2001, primary bladder neck obstruction was diagnosed in 41 men whose average age was 43 years. All of them were evaluated by a complete clinical history, American Urological Association (AUA) symptom score index, physical examination, uroflowmetry, transabdominal ultrasound prostatic volume determination, ultrasound post-void residual determination, videourodynamics including pressure-flow analysis and upper urinary tract screening with renal ultrasound or an excretory urogram. A full daily dose of alpha(1)-adrenergic blockers (alfuzosin or tamsulosin) was administered for at least 6 months. Successful treatment was defined as improved symptoms, voiding diary, maximum flow rate and pressure-flow parameters. Patients who did not gain improvement of symptoms with pharmacological treatment were offered surgery. RESULTS: Overall, pharmacological treatment was successful in 29/41 patients (70.7%) whereas bladder neck endoscopic incision was mandatory in 12/41 (29.3%). CONCLUSIONS: alpha(1)-Blockers were effective and safe for treating young and middle-aged men with symptomatic bladder neck obstruction.

Plasma chromogranin A in patients with prostate cancer improves the diagnostic efficacy of free/total prostate-specific antigen determination.

INTRODUCTION: We ascertained whether plasma chromogranin A enhances the power of serology assessing prostate cancer (PC). MATERIALS AND METHODS: We studied 56 PC and 83 benign prostatic hyperplasia (BPH) patients. In the sera we measured total prostate-specific antigen (tPSA) and free PSA (fPSA) and calculated the ratio between fPSA and tPSA (f/tPSA). In plasma samples the levels of chromogranin A (CgA) were also assayed. RESULTS: PC patients had higher CgA (p < 0.005) and tPSA (p < 0.05) levels, and a lower f/tPSA ratio (p < 0.001), than BPH patients. When f/tPSA and CgA were combined, the diagnostic sensitivity was enhanced (57-73%), while the specificity had only an 8% reduction (from 89 to 80%). CgA was only correlated to the Gleason PC score (p < 0.05). CONCLUSIONS: CgA determination in PC may enhance the diagnostic accuracy of the f/tPSA assay and provides useful information on the tumor grade.

Prognosis of bladder cancer. II. The fate of patients with T1b transitional cell bladder cancer.

We have reviewed the tumor progress in 46 patients who presented T1b lesions in a previous study on the prognosis of superficial bladder cancer. A group of 12 patients with single or very few localizations was treated by transurethral resection. Five patients progressed and were submitted to cystectomy. Two of these 5 patients died within 3 years of the surgical treatment. Twenty-seven patients with multiple lesions underwent cystectomy soon after the initial diagnosis. Nearly 30% experienced progression; 4 patients died within 4 years after cystectomy. A delayed cystectomy was performed in 7 patients with multifocal disease; in all but one the tumor progressed; 5 patients died between 7 and 28 months after the surgery.

Angiosarcoma of the bladder: a case report with regard to histologic and immunohistochemical findings.

Bladder angiosarcoma is an extremely rare neoplasia whose aggressive biological behavior follows that of other angiosarcomas. The second case of primary angiosarcoma of the bladder is reported pointing out the immunohistochemical characteristics of these neoplasias. Using immunoperoxidase staining techniques, Ulex lectin has proved to be a more sensitive marker for endothelial cells than factor VIII-related antigen, and it should be used as an additional marker for endothelial cell-derived tumors.

Prognosis of bladder cancer. III. The value of radical cystectomy in the management of invasive bladder cancer.

From January 1979 to June 1982, 141 consecutive patients with bladder transitional cell carcinoma were treated with a single stage lymphadenectomy plus radical cystectomy. The survival rate observed in our patients, based on the TNM classification, was comparable with that reported for other groups employing contemporary surgery. Survivorship for patients with deep invasive tumors was also estimated by breaking down the pT3 stage, and patients with tumor confined to the bladder wall (pT3a) were separately evaluated from those with tumor extended outside (pT3b). The results obtained with this subdivision showed that pT3a patients have almost the same survival rate as pT2 patients. From these results it is concluded that radical cystectomy is a satisfactory curative treatment of bladder cancer confined to the bladder wall, whatever the extension of the muscular involvement. Such considerations suggest that, in order to achieve a more objective analysis of the results after radical cystectomy for invasive bladder cancer, a modification of clinical staging is necessary. Moreover, a simplification of the classification methods should provide a better identification of the elements required to assess the prognosis and to improve treatment planning.

DNA content, nuclear grading and early tumor progression in renal cell cancer: a prospective study on frozen specimens.

Renal cell carcinoma is a neoplasia with an unpredictable behavior. Nuclear grade and pathologic stage are widely accepted as valuable prognostic factors. More recently DNA content has been proposed as an adjunctive parameter of the clinical course of the disease. In order to substantiate these findings we prospectively analyzed 36 frozen specimens from patients submitted to radical nephrectomy for renal cell carcinoma. The study population had a 2:1 male/female ratio with a median age of 57 years. Six of 33 patients died of tumor progression with a median survival time of 11 months. The tumor DNA index (DI) ranged from 0.86 to 2.06 with a mean coefficient of variation of 4.59. Ten cases (27.8%) had a diploid DNA content, whereas 26 (72.2%) showed a distinct aneuploid population. In 10 cases different DI values were observed in different samples from the same tumor. Aneuploidy was significantly associated with advanced pathologic stages, high nuclear grade, and tumor progression.