Untreated Gleason Grade Progression on Serial Biopsies during Prostate Cancer Active Surveillance: Clinical Course and Pathological Outcomes.

PURPOSE: We describe the outcomes of patients with low risk localized prostate cancer who were upgraded on a surveillance biopsy while on active surveillance and evaluated whether delayed treatment was associated with adverse outcome. MATERIALS AND METHODS: We included men in the study with lower risk disease managed initially with active surveillance and upgraded to Gleason score 3+4 or greater. Patient demographics and disease characteristics were compared. Kaplan-Meier curve was used to estimate the treatment-free probability stratified by initial upgrade (3+4 vs 4+3 or greater), Cox regression analysis was used to examine factors associated with treatment and multivariate logistic regression analysis was used to evaluate the factors associated with adverse outcome at surgery. RESULTS: The final cohort comprised 219 men, with 150 (68%) upgraded to 3+4 and 69 (32%) to 4+3 or greater. Median time to upgrade was 23 months (IQR 11-49). A total of 163 men (74%) sought treatment, the majority (69%) with radical prostatectomy. The treatment-free survival rate at 5 years was 22% for 3+4 and 10% for 4+3 or greater upgrade. Upgrade to 4+3 or greater, higher prostate specific antigen density at diagnosis and shorter time to initial upgrade were associated with treatment. At surgical pathology 34% of cancers were downgraded while 6% were upgraded. Cancer volume at initial upgrade was associated with adverse pathological outcome at surgery (OR 3.33, 95% CI 1.19-9.29, p=0.02). CONCLUSIONS: After Gleason score upgrade most patients elected treatment with radical prostatectomy. Among men who deferred definitive intervention, few experienced additional upgrading. At radical prostatectomy only 6% of cases were upgraded further and only tumor volume at initial upgrade was significantly associated with adverse pathological outcome.

Impact of Stress Urinary Incontinence After Radical Prostatectomy on Time to Intervention, Quality of Life and Work Status.

OBJECTIVE: To characterize the incidence of stress urinary incontinence (SUI) after radical prostatectomy (RP), its treatment, and impact on quality of life (QoL) and work status 1year after RP. MATERIALS AND METHODS: Prostate cancer patients treated by RP (1998-2016) were selected from CaPSURE. SUI was defined as any pads per day (ppd) 1 year after RP. SUI procedures were tracked by CPT codes (sling and artificial sphincter). Patients reported work status (full-time, part-time, unpaid), UCLA PCa Index urinary function (UF) and bother (UB) and SF36 Index physical function (PF). Associations of incontinence with UF, UB, and PF and work status changes were assessed (ANOVA). Lifetable estimates and Cox proportional hazards regression evaluated risk of undergoing SUI procedures. RESULTS: 664/2989 (22%) men treated with RP reported SUI at 1 year. More men with SUI had ≥GG2, intermediate to high-risk disease and non-nerve-sparing surgery (all P < .01). Cumulative incidence of SUI procedures was 1.4% at 10years after RP. Age (HR 2.68 per 10years, 95% CI 1.41-5.08) and number of ppd at 1 year (HR 3.20, 95% CI 2.27-4.50) were associated with undergoing SUI procedures. UF declined at 1year after RP, while UB and PF remained stable. UF, UB, and PF were inversely associated with number of ppd (all P < .01). Change in work status was not associated with incontinence or QoL scores. CONCLUSION: Incontinence affected QoL without impacting work status, suggesting that men with SUI after RP may continue working and go under-treated despite impact on QoL.

Association Between Common Urologic Medications and Onset of Alzheimer's Disease and Related Dementias in Men With Prostate Cancer Managed by Different Primary Treatment Modalities.

OBJECTIVE: To understand the relationship between common urologic medications phosphodiesterase-5 inhibitors (PDE5i) and anticholinergics (AC) and risk of dementia onset in men who underwent different primary treatments for prostate cancer. MATERIALS AND METHODS: Patients (>50years) with prostate cancer (1998-2022) without Alzheimer's disease or related dementias were selected from Cancer of the Prostatic Strategic Urologic Research Endeavor Registry. Minimum medication use was 3months. Fine-Gray regression was performed to determine the association between medication exposure and dementia onset ≥12months after primary treatment in men matched on age, race, comorbid conditions, smoking, and type of clinical site, with competing risk of death. RESULTS: Among 5937 men (53% PDE5i; 14% AC), PDE5i users were younger (63 vs 70, P < .01) with less CAD, CVA, DM (all P < .01); AC users were older (68 vs 66, P < .01) with higher incidence of comorbidities (P < .01). Median months of use was 24.3 (IQR 12.1, 48.7) for PDE5i and 12.2 (IQR 6.1, 24.3) for AC users. Cumulative incidence of Alzheimer's disease or related dementias was 6.5% at 15years. PDE5i (P = .07) and AC (P = .06) were not associated with dementia regardless of primary treatment modality. CONCLUSION: In this retrospective cohort study, PDE5i and AC use do not appear independently associated with risk of dementia. Notably, our cohort was generally healthy and younger which may limit our ability to detect significance. We recommend prospective investigation into association between PDE5i and dementia and advise continued judicious stewardship of AC in older patient populations.

Centromeric copy number of chromosome 7 is strongly correlated with tumor grade and labeling index in human bladder cancer.

The relationship between interphase cytogenetics and tumor grade, stage, and proliferative activity was investigated in 27 transitional cell carcinomas of the urinary bladder. Using fluorescence in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 9, and 11 was detected within interphase nuclei in touch preparations from tumor biopsies. Monosomy of chromosome 9 was detected in 9 of 22 cases (41%), while tetrasomy for chromosomes 7 and 11 was detected in 10 of 26 (38%) and 6 of 23 (26%) cases, respectively. Copy number of chromosome 7 was the most highly correlated with increasing tumor grade (r2 = 0.616, P less than 0.001, Spearman rank correlation) or increasing pathological stage (r2 = 0.356, P less than 0.002). Copy number for chromosome 9 did not correlate with either grade or stage (P greater than 0.05). Tumor labeling index (LI) was determined after in vitro 5-bromodeoxyuridine incorporation, while proliferating cell nuclear antigen LI was determined immunohistochemically. Increasing LI by either method correlated with increasing copy number for all three chromosomes tested (r2 = 0.473, P less than 0.002 for 7; r2 = 0.384, P less than 0.01 for 11; and r2 = 0.316, P less than 0.05 for 9). Since high tumor grade, stage, and LI are all indicative of more aggressive tumor behavior and worse prognosis, these findings suggest that polysomy, especially for chromosome 7, may be highly predictive for bladder tumor aggressiveness.

Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell.

Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping.

A newly developed method of comparative genomic hybridization (CGH) employing quantitative statistical comparisons was applied to DNA from two different types of advanced prostate cancer tissue. Multiple CGH analyses were obtained for each chromosome in each tumor, and the results of point-by-point comparison of the mean tumor:normal color ratio to a control normal:normal color ratio in each of 1247 evenly distributed data channels constituting the entire human genome were interpreted as loss, gain, or no change in copy number in the tumor genome. Group I tissue was obtained from prostate cancer metastases from 20 patients, 19 of whom had received no prior prostate cancer treatment. This DNA also was analyzed by Southern and microsatellite allelotyping at 53 different loci on 20 different chromosome arms. CGH results agreed with allelotyping results at 92% of the informative loci studied. These samples, which contained highly enriched tumor DNA, showed the highest rates of alteration yet reported in several chromosomal regions known to be altered frequently in prostate cancer: 8q gain (85%), 8p loss (80%), 13q loss (75%), 16q loss (55%), 17p loss (50%), and 10q loss (50%). Group II tissue was obtained predominately from primary or recurrent tumor from 11 patients who had been treated with long-term androgen-deprivation therapy and developed androgen-independent metastatic disease. Quantitative CGH analysis on DNA from these tissues showed chromosomal alterations that were very similar to those found in group I, suggesting that untreated metastatic tumors contain the bulk of chromosomal alterations necessary for recurrence to occur during androgen deprivation. In the entire data set, a number of previously undetected regions of frequent loss or gain were identified, including losses of chromosomes 2q (42%), 5q (39%), 6q (39%), and 15q (39%) and gains of chromosomes 11p (52%), 1q (52%), 3q (52%), and 2p (45%). Chi-squared analysis showed a significantly higher frequency of gain of the 4q25-q28 region in tumors from African-American patients, indicating a possible oncogene whose activation may play a role in the higher rate of progression seen in this ethnic group. Additional study of these frequently altered regions may provide insight into the mechanism of prostate cancer progression and lead to important tools for tumor-specific prognosis and therapy.

Genetic alterations in primary bladder cancers and their metastases.

Bladder cancer progression is thought to be associated with sequential genetic events. To search for the specific genetic changes associated with the metastatic process, comparative genomic hybridization was performed on 22 primary tumors and 24 metastases (10 distant and 14 nodal metastases) from 17 patients with stage pT2-4 bladder cancer. There was a striking similarity between the genetic alterations present in the primary and metastatic tumor samples from the same patient. The mean number of genetic changes/tumor was 12.2 for primary tumors and 11.7 for metastases. There was a strong concordance in the specific aberrations present in each patient's primary and metastatic lesions (mean, 75%). Concordance was also high among multiple sites from an individual primary tumor (mean, 96%) and multiple metastases from the same patient (mean, 75%). There were no specific genetic changes overrepresented in the metastases compared with their primary tumors. Genetic alterations present in more than 40% of tumors included gains on 6p, 8q, 10q, and 17q and losses involving 8p, 10q, and Y. Two regions of high-level amplification were common: (a) 10q22.1-q23.1 (32.6%); and (b) 17q11-21.3 (23.9%; the locus of erbB-2). A summary statistic was developed to quantitate the degree of clonal relationships between biopsies from the same patient. These data support a model in which minimal clonal evolution occurs in the metastatic tumor cell population after the metastatic event. When comparing primary cancers from patients with and without metastases, however, several unique genetic changes were identified in those cancers with metastases, suggesting that these loci may harbor genes important to the metastatic process.

A diagnosis of prostate cancer and pursuit of active surveillance is not followed by weight loss: potential for a teachable moment.

BACKGROUND: Obesity is a risk factor for incident prostate cancer (PC) as well as risk of disease progression and mortality. We hypothesized that men diagnosed with lower-risk PC and who elected active surveillance (AS) for their cancer management would likely initiate lifestyle changes that lead to weight loss. METHODS: Patients were enrolled in the Prostate Active Surveillance Study (PASS), a multicenter prospective biomarker discovery and validation study of men who have chosen AS for their PC. Data from 442 men diagnosed with PC within 1 year of study entry who completed a standard of care 12-month follow-up visit were analyzed. We examined the change in weight and body mass index (BMI) over the first year of study participation. RESULTS: After 1 year on AS, 7.5% (33/442) of patients had lost 5% or more of their on-study weight. The proportion of men who lost 5% or more weight was similar across categories of baseline BMI: normal/underweight (8%), overweight (6%) and obese (10%, χ2 test P=0.44). The results were similar for patients enrolled in the study 1 year or 6 months after diagnosis. By contrast, after 1 year, 7.7% (34/442) of patients had gained >5% of their weight. CONCLUSIONS: Only 7.5% of men with low-risk PC enrolled in AS lost a modest (⩾5%) amount of weight after diagnosis. Given that obesity is related to PC progression and mortality, targeted lifestyle interventions may be effective at this 'teachable moment', as men begin AS for low-risk PC.

Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies.

BACKGROUND: Expanding interest in and use of active surveillance for early state prostate cancer (PC) has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinicopathological features and validate its utility as a clinical grade test in predicting cancer-specific outcomes. METHODS: After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (three cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinicopathological factors and recurrence-free survival (RFS) including biochemical recurrence, metastasis or PC death (7-year median follow-up). RESULTS: In 1004 PCs (∼4000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (P<0.0001), seminal vesicle invasion (SVI, P=0.02), extracapsular extension (ECE, P<0.0001) and Gleason score (GS, P<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence-free, overall and disease-specific survival by multivariable Cox proportional hazard model (hazards ratio (HR)=1.04-1.1, P=0.02-0.0008). High Ki67 score (defined as ⩾5%) was significantly associated with worse RFS (HR=1.47, P=0.0007) and worse overall survival (HR=2.03, P=0.03). CONCLUSIONS: In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE and greater probability of recurrence.

Preliminary evaluation of prostate cancer metastatic risk biomarkers.

Prostate cancer patients at high risk of metastasis need to be identified as early as possible since metastasis is invariably fatal. Treatment could be tailored to risk. Recent array comparative genomic hybridization (aCGH) studies of primary and metastatic prostate tumors identified 39 BAC clones capable of detecting genomic signatures of metastasis. We termed these loci the genomic evaluators of metastatic CaP (GEMCaP). Risk assessments were made on a set of men who were managed with radical prostatectomy. We compared the utility of GEMCaP loci and the Kattan nomogram, a common risk assessment tool, in relation to biochemical outcome. This preliminary evaluation experiment suggests we can use aCGH to detect genomic signatures of metastasis in primary tumors with an accuracy of 78%. The classification accuracy for the Kattan nomogram was 75%. Therefore, validation of GEMCaP is warranted in a larger, appropriately designed cohort.

Minichromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer.

The minichromosome maintenance (MCM) proteins are highly conserved proteins essential for initiating and regulating eukaryotic DNA replication. Recent studies have demonstrated the potential use of MCM proteins as markers of proliferation. We characterized the pattern of Mcm 2 staining in benign and malignant prostate tissues and examined the role of Mcm 2 expression in disease-free survival after surgery in men with localized prostate cancer. Tumors from 92 patients who underwent radical prostatectomy for prostate cancer (median follow-up of 54 months) were examined for Mcm 2 expression by immunohistochemistry using a monoclonal antibody. Prostate tissue from five men without histopathological evidence of prostate cancer was also stained for Mcm 2. Mcm 2 expression was quantified by calculating a labeling index, and patients were grouped according to degree of staining. An analysis of the association between Mcm 2 expression with traditional clinicopathological characteristics of prostate cancer was carried out. A Cox proportional hazards analysis was performed to determine whether Mcm 2 staining was a significant independent predictor of disease-free survival. Mcm 2 expression is low (<2%) and limited to the basal cell layer in nonmalignant prostate glands. Mcm 2 expression is consistently increased in malignant glands and is significantly associated with disease-free survival in univariate (P = 0.002) and multivariate (P = 0.01) analyses. Patients with high Mcm 2 expression exhibited shorter disease-free survival. Mcm 2 expression was not associated with any traditional clinical or pathological factors and therefore is an independent predictor of survival in these patients with prostate cancer. These data support evidence that Mcm 2 may serve as a novel proliferation marker in the prostate. Mcm 2 expression is an independent predictor of disease-free survival after definitive local therapy and has potential as a molecular marker for clinical outcome in prostate cancer.

Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse. An observational follow-up study.

BACKGROUND: The optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse is unknown. METHODS: We identified men with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE) study who would have been eligible (⩽ cT3aN0M0, primary radical prostatectomy or radiotherapy, PSA relapse as the only evidence of recurrence) for a randomised trial comparing 'immediate' versus 'deferred' ADT initiation. We emulated such trial by assigning patients to the 'immediate' strategy if they initiated ADT within 3 months of PSA relapse and to the 'deferred' strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time. We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting. RESULTS: Of 2096 eligible patients (median age 69, interquartile range 63-75 years), 88% were white, 35% had a Gleason score ⩾ 7, 69% were treated with radical prostatectomy and 31% received radiotherapy only as primary treatment. The mean time from primary treatment to PSA relapse was 37.4 (standard deviation [SD] 34.2) months. Mean follow-up from primary treatment was 91.4 (SD 48.4) months. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52-1.60), which would be translated into a similar 5-year survival (difference between groups: -2.0% (95% CI: -10.0 to 5.9%). CONCLUSION: Our analysis suggests that prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression.

Can hematuria be a predictor as well as a symptom or sign of bladder cancer?

In a case-control study of urinalysis screening in the prevention of death from bladder cancer, hematuria was present in a higher proportion of cases than controls as long as five or six years before the diagnostic evaluation that led to the diagnosis of bladder cancer. In a separate cohort study data base that permitted the follow-up of 1046 persons with a physician's diagnosis of hematuria, 11 cases of bladder cancer were diagnosed more than two (mean 7.4) years after the hematuria diagnosis (4.3 cases expected; age-sex standardized morbidity ratio, 2.5; 95% confidence interval, 1.3-4.5). Bladder cancer was ruled out initially by cystoscopy in 8 of the 11 cases. Although we cannot be certain that preexisting bladder cancer or bladder cancer risk factors did not cause the bleeding, we hypothesize that hematuria can be a predictor as well as a manifestation of bladder cancer, based on a tendency for bladder mucosa with premalignant changes to bleed. The implications for screening and clinical practice remain to be determined.

The response of the urinary bladder, urethra, and ureter to radiation and chemotherapy.

A comprehensive review of the physiological and clinical response of the urinary bladder, ureter, and urethra to radiation and chemotherapy is presented. The clinical syndromes that follow therapy for cancer of the bladder, prostate, and cervix are reviewed in detail. Methods of assessing, scoring, and managing toxicity are discussed.

Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer.

PURPOSE: To evaluate the predictive value of an empirically derived equation for identifying patients with clinically localized prostate cancer at low and high risk for harboring occult lymph node metastasis. METHODS AND MATERIALS: A simple equation for estimating the risk of positive lymph nodes was empirically derived from a nomogram published by Partin et al. demonstrating the value of combining the pre-treatment prostate specific antigen and Gleason Score in predicting the risk of lymph node metastasis for patients with clinically localized prostate cancer. The risk of positive nodes (N+) was calculated using the equation; N+ = 2/3(PSA) + (GS-6) x 10, where PSA and GS are the pre-treatment prostate specific antigen and Gleason Score respectively, and the calculated risk is constrained between 0-65% for a PSA < or = 40 ng/ml (as in the nomogram). To test the general applicability of this equation, we reviewed the pathologic features of 282 of our patients who had undergone a radical prostatectomy. RESULTS: Based on 212 patients for whom the pre-operative prostate specific antigen's and Gleason Scores were available, we identified 145 patients with a calculated risk of positive nodes of < 15%, (low risk group) and 67 patients with a calculated risk as > or = 15% (high risk group). The observed incidence of positive nodes was 6% and 40% among the low and high risk groups respectively (p < 0.001). When used alone neither clinical stage, pre-treatment prostate specific antigen nor the pre-treatment Gleason Score was as useful in identifying the largest low and high risk groups. CONCLUSION: Using the equation described we confirmed the general applicability of the nomogram reported by Partin et al. and identified patients at low and high risk for lymph node involvement. Based on these data we have adopted a policy of omitting whole pelvic irradiation in patients identified as low risk.

A study of reproductive function in patients with seminoma treated with radiotherapy and orchidectomy: (SWOG-8711). Southwest Oncology Group.

PURPOSE: The results of Southwest Oncology Group Study 8711 (Group 2B) are presented. The objective was to evaluate the natural history of sperm concentration and selected hormonal parameters in patients with testicular cancer treated with orchiectomy and radiotherapy. METHODS AND MATERIALS: Of a total of 207 patients enrolled on SWOG 8711, 53 pure seminoma patients were identified who were treated with orchiectomy and radiotherapy only. Sperm concentration, follicle-stimulating hormone (FSH) levels, and sexual satisfaction scores were the main parameters followed. RESULTS: A fraction of the patients were infertile prior to receiving radiotherapy. Our analysis indicates that incidental radiation dose to the remaining testicle affects time to recovery of fertility, and at an aggregate level, changes in FSH mirror changes in sperm concentration over time. This phenomenon is the same as that described in patients free from testicular cancer. These men evaluated their sexual activity as good after orchidectomy. CONCLUSION: Our data support the use of clamshell-type testicular shields as a means of providing maximum protection to the remaining testicle.

Modification of cardiovascular responses to histamine by dithiothreitol.

1 Histamine produced dose-dependent contractile responses on both isolated perfused ear arteries and aortic strips of the rabbit. These responses were blocked by mepyramine and potentiated by both metiamide and dithiothreitol. 2 In the presence of maximum potentiation by metiamide, dithiothreitol still potentiated the contractile response to histamine of both preparations. 3 In the presence of mepyramine, histamine produced dose-dependent reductions in the contractile response to noradrenaline. This vasodilator action of histamine was abolished by metiamide but was unaffected by dithiothreitol. 4 The vasodilator action of histamine on the human isolated perfused temporal artery and the positive inotropic effect of histamine on the isolated spontaneously beating atria of the rabbit were blocked by metiamide but unaffected by dithiothreitol. 5 It is concluded that the rabbit aorta, like the ear artery, contains both H1 and H2 histamine receptors and that dithiothreitol potentiates cardiovascular responses mediated by H1-receptors but not by H2-receptors.

Comparison of five histopathologic methods to assess cellular proliferation in transitional cell carcinoma of the urinary bladder.

Transitional cell carcinomas of the urinary bladder vary in their biologic potential, which may be correlated with the grade and stage of the tumor. Cellular proliferation may prove to be another measure of predicting tumor biologic potential. We have compared five different methods to assess proliferation in 26 tumors and correlated these results with tumor grade and stage. A portion of each tumor was incubated in vitro with bromodeoxyuridine (BrdUrd). For each tumor this was compared with at least three of the following four other markers of proliferation: mitotic count, silver-stained nucleolar organizer regions, immunohistochemical staining with Ki67, and proliferating cell nuclear antigen. Statistical correlations were seen between tumor grade and stage and these markers. There were strong correlations between the BrdUrd labeling index (LI) and both the Ki67 LI and proliferating cell nuclear antigen LI. The correlation between the BrdUrd LI and mitotic count was more tenuous; no significant correlation was found between BrdUrd LI and silver-stained nucleolar organizer region count. The correlation between these measurements of proliferation and tumor grade and stage was less strong. Our data suggest that cellular proliferation of transitional cell carcinomas can be reliably assessed with several different markers and that most of these markers can be correlated with tumor grade but not with stage.

Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma.

In an effort to determine whether or not any characteristic chromosomal abnormalities exist in renal cancer, cytogenetic findings were correlated with tumor histology in nine cases of renal adenocarcinoma. Metaphase preparations adequate for analysis were obtained from cultures harvested between day 3 and day 21. Model chromosome number was diploid in three cases, hypodiploid in three, and hyperdiploid in the remaining three. One clear cell adenocarcinoma failed to reveal any chromosomal abnormality. Two tumors, a tubular/papillary carcinoma and an acinar/papillary carcinoma, showed the clonal abnormalities del(1)(p2l),+2,+7,+8,+12,+13,+16,+17,-21 and t(2;10)(q14-21;q26),+7q,+11q,-18, respectively. Interestingly, five of six clear cell tumors studied had clonal abnormalities affecting the short arm of chromosome #3 in the 3p12-21 region, and in the remaining case, of 15 karyotyped metaphases suitable for interpretation, one showed a deletion in 3p. These data indicate that clear cell carcinoma of the kidney may be associated with a nonrandom chromosomal abnormality involving the 3p12-14 region.