Cytogenetic analysis of prostate carcinoma by fluorescence in situ hybridization.
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Adenocarcinoma↗
Biomedical subjects
M M Lieber
Publications and source records attributed to M M Lieber.
Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men.
OBJECTIVE: To determine whether the age-specific reference ranges for serum prostate-specific antigen (PSA) concentration generated for white men are applicable to other races. PATIENTS AND METHODS: Three-hundred and thirty-five healthy Japanese men, aged 40-79 years, residing in the small fishing village of Shimamaki-mura, Japan, agreed to enter this prospective, community-based study. All underwent a detailed clinical evaluation that included a serum PSA determination, a digital rectal examination and a transrectal ultrasound. Two-hundred and eighty-six (85%) completed the prostatic evaluation and had no evidence of prostate cancer by any one of the three diagnostic tests; these men formed the study population on which all analyses were performed. RESULTS: The serum PSA concentration correlated directly with patient age (r = 0.33; P < 0.001) and prostatic volume (r = 0.57; P < 0.001). PSA density (PSAD) also was directly proportional to age (r = 0.30; P < 0.001). Adjusting for age, the serum PSA concentration was lower for Japanese men than for white men (P < 0.001). Thus, the recommended age-specific reference ranges (95th percentile) for serum PSA for Japanese were lower as well: 0.0-2.0 ng/mL for 40-49 years; 0.0-3.0 ng/mL for 50-59 years; 0.0-4.0 ng/mL for 60-69 years; and 0.0-5.0 ng/mL for 70-79 years. Based on transrectal ultrasound-volume determinations, the lower serum PSA concentrations in Japanese men are due in large part to their smaller prostate glands as compared with white men (P < 0.001). CONCLUSIONS: These findings confirm the earlier observations that serum PSA, prostatic volume and PSAD are age-dependent. However, because of physiological differences among the two races, partly due to the size of the prostate gland, the age-specific reference ranges for serum PSA are lower for Japanese men than for white men. Because of these racial differences, it is now crucial to conduct a similar investigation among black men.
Adult↗
Sexual function of men ages 40 to 79 years: the Olmsted County Study of Urinary Symptoms and Health Status Among Men.
OBJECTIVES: Knowledge of male sexual function is somewhat limited because of a lack of current population-based data. This study provides information on sexual function and satisfaction in a population-based sample of men. METHODS: Men aged 40 to 79 years (n = 2115) were selected randomly from the Olmsted County population for the baseline component of a prospective cohort study (the Olmsted County Study of Urinary Symptoms and Health Status Among Men) during 1989-1990. The men completed a self-administered questionnaire that included questions about sexual concerns, performance, satisfaction, drive, and erectile dysfunction. RESULTS: For all five sexual parameters queried, the prevalence of problems and dysfunction increased with age. A comparison of men aged 70 to 79 years with men aged 40 to 49 years suggested that older men were more worried about sexual function (46.6% vs 24.9%), had worsened performance compared with a year ago (30.1% vs 10.4%), expressed extreme dissatisfaction with sexual performance (10.7% vs 1.7%), had absent sexual drive (25.9% vs 0.6%), and reported complete erectile dysfunction when sexually stimulated (27.4% vs 0.3%). Logistic regression analyses suggested that sexual dissatisfaction was significantly associated with erectile dysfunction, decreased libido, and the interaction between erectile dysfunction and libido, but not age. CONCLUSIONS: These population-based cross-sectional data corroborate the previously reported age-related decrease in sexual function. The age-related increase in dissatisfaction could, however, be accounted for primarily by the age-related increase in erectile dysfunction, decreased libido, and the interaction between erectile dysfunction and decreased libido.
Adult↗
The role of community-based longitudinal studies in evaluating treatment effects. Example: benign prostatic hyperplasia.
To determine the appropriateness and effectiveness of medical interventions, it is necessary to understand both the natural history of the conditions the interventions are intended to treat or prevent, and the normal reference ranges of tests used in diagnosis and management. The acquisition of this information through clinic-based studies can yield misleading conclusions owing to selection bias. What appears to be intervention-related variation in outcomes may be variation in the magnitude and form of selection bias. To minimize selection bias, population-based studies are required. Results from the Olmsted County Study of Urinary Symptoms and Health Status Among Men were used to show how a population-based longitudinal study of the natural history of benign prostatic hyperplasia (BPH) can complement research programs of the BPH Patient Outcomes Research Team. Population-based studies of disease natural history are a necessary part of medical outcomes research, and deserve greater emphasis in the medical treatment effectiveness research initiative of the Agency for Health Care Policy and Research.
Community Health Planning↗
Morbidity of contemporary radical retropubic prostatectomy for localized prostate cancer.
Complication rates in 1,000 consecutive patients who underwent radical retropubic prostatectomy for clinically localized prostate cancer between November 1989 and January 1992 were assessed and compared to complication rates in a historical group of patients operated on by primarily the same surgeons prior to 1987. In the contemporary series, there were no operative deaths, only 22% of patients required blood transfusion, and only six (0.6%) patients suffered rectal injuries. Early complications, including myocardial infarction, pulmonary embolism, bacteremia, and wound infection, occurred in less than 1% of patients. Vesical neck contracture, the most common late complication, developed in 87 patients (8.7%). At 1 year post-surgery, 80% of patients were completely continent, and fewer than 1% were totally incontinent.
Aged↗
Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ hybridization are markers of poor prognosis in prostate cancer.
Fluorescence in situ hybridization is a new methodology which can be used to detect cytogenetic anomalies within interphase tumor cells. We used this technique to identify nonrandom numeric chromosomal alterations in tumor specimens from the poorest prognosis patients with pathological stages T2N0M0 and T3N0M0 prostate carcinomas. Among 1368 patients treated by radical prostatectomy, 25 study patients were ascertained who died most quickly from progressive prostate carcinoma within 3 years of diagnosis and surgery. Tumors from 25 control patients who survival for more than 5 years and who were matched for age, tumor histological grade, and pathological stage also were evaluated. The tumors from all 25 (100%) poor prognosis patients and from 11 of 25 (44%) control patients were found to be aneuploid by fluorescence in situ hybridization (P < 0.0001). Alterations of chromosome 7 were observed in 24 of the tumors (96%) from the poor prognosis patients versus 3 tumors (12%) from the control group (P < 0.0001). Moreover, a characteristic aneuploidy pattern with multiple abnormal chromosomes and a hypertetrasomic population was generally found in tumors from the poor prognosis patients. This preliminary study suggests that fluorescence in situ hybridization studies of prostate cancer specimens may help to identify those patients at highest risk for early cancer death.
Aged↗
Potential markers of prostate cancer aggressiveness detected by fluorescence in situ hybridization in needle biopsies.
Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 11, and 12 was used to evaluate multiple 18-gauge needle biopsy cores from 50 randomly selected radical prostatectomy specimens. FISH analysis detected 26 diploid (52%), 7 tetraploid (14%), and 17 aneuploid tumors (34%). The FISH results were concordant with flow cytometric (FCM) DNA content measurements of the corresponding prostatectomy specimens for 31 tumors. For the 19 FISH/FCM discordant tumors, FISH was more sensitive than FCM for detecting ploidy anomalies. Common numerical chromosome alterations were gains of chromosomes 7 and 8, which were found in 13 (76%) and 10 (59%) aneuploid tumors, respectively. Gain of chromosome 7 was strongly associated with higher Gleason score (> or = 8) (P < 0.0001) and with advanced tumor pathological stages (stages T3 + T4; P < 0.01). Gain of chromosome 8 also correlated with higher Gleason score (P < 0.01). FISH showed intratumoral ploidy heterogeneity in 3 of 41 (7%) studied tumors. Among 17 noncancerous adjacent tissue specimens, chromosome alterations were observed in one, which contained high-grade prostatic intraepithelial neoplasia. Combined FISH and fluorescent leukocyte common antigen staining showed that infiltrating leukocytes do not contribute to the observed gains of chromosomes 7 and 8 in prostate cancer tissue. These results demonstrate that (a) FISH analysis of prostate needle biopsy-sized specimens can be a practical, sensitive method for determination of nuclear ploidy and numerical chromosome alterations; and (b) gains of chromosomes 7 and 8 are common numerical alterations of prostate cancer cells and may be potential markers of tumor behavior and patient prognosis.
Biopsy, Needle↗
Prostate cancer in Rochester, Minnesota (USA), from 1935 to 1989: increases in incidence related to more complete ascertainment.
Prostate cancer incidence among White men in the United States climbed steadily from 45 per 10(5) person-years (PY) during 1945-54 to 102 per 10(5) PYs in 1988. To determine whether this increase might be the result of changing diagnostic practices, we examined trends in incidence and method of diagnosis in Rochester, Minnesota (US), from 1935 to 1989. We found a parallel increase in Rochester in non-autopsy diagnoses from 44 (95 percent confidence interval [CI] = 29-58) cases per 10(5) PYs in 1935-44 to 71 (CI = 52-89) cases per 10(5) PYs in 1985-87 which was driven by diagnoses prompted by digital rectal examination. There was no evidence that an increasing proportion of cases was found as the result of procedures to treat the symptoms of benign prostatic hyperplasia. Including autopsy diagnoses, incidence was stable over this extended interval and was 77 per 10(5) PYs (CI = 58-97) in 1935-44 and 72 per 10(5) PYs (CI = 53-91) in 1985-87. Incidence more than doubled after introduction of diagnostic serum prostate-specific antigen (PSA) assay and was 179 per 10(5) PYs (CI = 145-214) in 1988-89. We conclude that prostate-cancer incidence rates are influenced strongly by diagnostic practices and that national increases could reflect, to a large extent, more complete and earlier ascertainment rather than more frequent disease.
Adult↗
Seminal vesicle fistula following abdominoperineal resection for recurrent adenocarcinoma of the rectum. Report of a case.
PURPOSE: Fistula formation between the seminal vesicles and a pelvic abscess after abdominal perineal resection for recurrent rectal cancer is reported in a 32-year-old male previously treated with low anterior resection, chemotherapy, and radiation. METHODS: The case history was reviewed for clinical presentation, radiologic studies, and laboratory data. RESULTS: Successful management of this previously unreported complication included percutaneous abscess drainage, antimicrobial therapy, and oral administration of Proscar (Merck, Sharpe & Dohme, Rathway, NJ). CONCLUSION: Multiple factors predisposed this patient's development of a seminal vesicle fistula. These include extensive scarring from previous surgery, pelvic radiation, and an immunologically depressed status. The efficacy of Proscar in the successful management of this case remains unknown.
Adenocarcinoma↗
Comparison of fluorescence in situ hybridization with flow cytometry and static image analysis in ploidy analysis of paraffin-embedded prostate adenocarcinoma.
Nuclear DNA ploidy has been shown to have an important prognostic association for patients with adenocarcinoma of the prostate. Flow cytometry and static image analysis are ploidy methods that have been used in prostate carcinoma. Fluorescence in situ hybridization (FISH) using chromosome-specific probes can be used to evaluate the ploidy of interphase nuclei. In this study FISH was compared with flow cytometry and static image analysis in determining ploidy in paraffin-embedded tissue from 34 prostatic adenocarcinomas. Ploidy status using FISH was determined by enumerating centromeres of two chromosomes (8 and 12) by use of directly-labeled alpha-satellite DNA probes in isolated whole nuclei obtained by the Hedley technique. All three methods identified 11 of 34 cases as diploid and 17 of 34 cases as nondiploid (82% concordance). Six cases were discordant; two cases had discrepant results by each method. Ploidy classification as determined by FISH had an 88% concordance with ploidy classification by either flow cytometry or static image analysis. In conclusion, FISH was found to be a sensitive method of ploidy analysis in isolated paraffin-embedded nuclei from prostate adenocarcinomas. When the chromosomes commonly involved in aneuploidy have been identified in prostate adenocarcinoma, FISH has the potential to provide greater sensitivity for aneuploidy detection compared with currently available methods.
Adenocarcinoma↗
Clinical significance of nuclear DNA ploidy pattern in nonseminomatous germ cell testicular tumors.
OBJECTIVE: To evaluate the clinical significance of DNA ploidy pattern for patients with nonseminomatous germ cell testicular tumors who did not receive platinum-based chemotherapy. METHODS: Flow cytometric nuclear DNA ploidy analysis of paraffin-embedded tissue blocks were used. RESULTS: All patients underwent radical orchiectomy with or without retroperitoneal lymphadenectomy between 1960 and 1980. Mean follow-up time was eight years. Nineteen percent of the tumors were DNA diploid and 81 percent were DNA aneuploid. Signs of local tumor extension (spermatic cord involvement or vascular invasion) were found in 20 tumors, all were classified as DNA aneuploid (P < 0.04). After primary treatment 9 patients who were clinically cured experienced disease progression; only 1 of them had DNA diploid tumor; the rest were DNA aneuploid (P < 0.05). The ten-year survival rate was higher for patients having DNA diploid tumors compared with those with DNA aneuploid neoplasms (86% versus 53 percent, P < 0.02). CONCLUSIONS: The results of this retrospective study indicate that nuclear DNA content provide important information concerning the natural history and biology of nonseminomatous germ cell testicular tumor.
Adult↗
Cigarette smoking and prostatism: a biphasic association?
OBJECTIVE: To evaluate the association between cigarette smoking and prostatism in a community-based setting using standardized urinary symptom scores, peak urinary flow rates, and prostatic volume as indicators of disease. METHODS: A population-based cohort of 2,115 Caucasian men aged forty to seventy-nine years from Olmsted County, Minnesota, was administered a previously validated questionnaire that elicited information on frequency of urinary symptoms (approximating the American Urological Association's symptom index), and a detailed history on cigarette smoking, including both amount and pack-years of smoking. Peak urinary flow rates were measured by a standard uroflowmeter (Dantec 1000). The prostatic volume was measured for a subsample of 471 men by transrectal ultrasound. RESULTS: Compared to never-smokers, smokers were less likely to have moderate to severe urinary symptoms (age-adjusted odds ratio 0.82; 95% confidence interval [CI] 0.61 to 1.08). This varied by smoking intensity, however; in men who smoked less than 1 pack a day the age-adjusted odds ratio was 0.53 (95% CI 0.33 to 0.83) and among men smoking 1 to 1.4 packs a day, the odds ratio was 0.87 (95% CI 0.56 to 1.36). For men who smoked 1.5 packs or more a day, the odds ratio was elevated at 1.32 (95% CI 0.84 to 2.07). Smokers were less likely to have peak flow rates less than 15 mL/sec compared with never-smokers (age- and voided volume-adjusted odds ratio 0.48; 95% CI 0.35 to 0.66), or prostatic volume greater than 40 mL (odds ratio 0.54; 95% CI 0.19 to 1.55). CONCLUSIONS: These data from a community-based sample suggest that light or moderate smokers are less likely to have moderate to severe prostatism, whereas heavy smokers are at least as likely to have moderate to severe prostatism compared with never-smokers.
Adult↗
Natural history of prostatism: worry and embarrassment from urinary symptoms and health care-seeking behavior.
OBJECTIVE: To assess the interrelationships among psychosocial symptoms of worry and embarrassment about urinary function, prevalent urinary symptoms, psychological well-being, and health care-seeking behavior in a population-based cohort of men. METHODS: A cohort of 2,119 men aged forty to seventy-nine years, randomly selected from the Olmsted County, Minnesota population between December 1989 and March 1991, were administered a previously validated questionnaire that elicited information about the frequency of urinary symptoms, the degree to which they were perceived as a bother, and if the participant had seen a doctor in the previous twelve months for evaluation of any of these urinary symptoms. Psychological well-being was assessed by a subset of the Psychological General Well-Being Index, and sociodemographic information was also sought. RESULTS: Urinary symptom indices (measured by American Urological Association frequency and bother scores and psychological general well-being subscales) were significantly associated with worry and embarrassment about urinary symptoms in bivariate analyses. Multiple logistic regression analyses demonstrated that men with moderate or severe urinary symptoms or impaired psychological well-being were more likely to be worried or embarrassed about their urinary symptoms than men with mild symptoms. Furthermore, men who were worried about their urinary function were more likely to have sought medical care for their symptoms than men who were not worried. The association between health care-seeking behavior and embarrassment was especially strong among men with little bother associated with their urinary symptoms. CONCLUSIONS: Worry and embarrassment about urinary symptoms reflect quality-of-life issues that appear important in the health care-seeking behavior of men with prostatism. The results underscore findings that prevalent urinary symptoms alone do not determine a man's health care-seeking behavior, and treatment for psychosocial symptoms may be beneficial in some men with symptoms of prostatism.
Adult↗
Effect of several recruitment strategies on response rates at baseline in a prospective cohort investigation. The Olmsted County Study of Urinary Symptoms and Health Status among Men.
Epidemiologic survey response rates were studied in relation to maneuvers introduced to improve acceptance: (a) variation in invitation letters, (b) the use of a brochure with the recruitment mailing, and (c) options for interview location. The baseline population-based survey of a prospective cohort investigation of the natural history of benign prostatic hyperplasia was used. Invitations to participate were mailed to eligible, randomly selected men aged 40 to 79 years from the Olmsted County, Minnesota, population during 1989 to 1991. Of the 3874 men identified, 2119 (55%) participated. Overall, there was no difference in response rate according to invitation characteristics (chi 2(5) = 8.02, P = 0.16). Nevertheless, response rates varied with age (chi 2(7) = 30.9, P < 0.001) and home location (rural versus Rochester city; chi 2(1) = 76.9, P < 0.001). This suggests the innovations used to bolster acceptance did not materially improve response rates. Further, since response rates were highest for men aged 60 to 74 years, men with more symptoms and free time may have joined the cohort more often than others.
Adult↗
Chromosomal aneusomies detected by fluorescent in situ hybridization analysis in clinically localized prostate carcinoma.
Fluorescent in situ hybridization using 12 chromosome enumeration probes (for chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, X and Y) was used to evaluate fresh tumor touch preparations from 40 randomly selected radical prostatectomy specimens. Of the tumors 16 (40%) contained chromosomal aneusomies. Chromosome 8 was aneusomic in 9 tumors (23%). Gain of chromosome 7 was observed in 8 tumors (20%). Chromosome 17 was aneusomic in 4 cases, and chromosomes 10, 11, 12, 18 and Y were each aneusomic twice. Loss of chromosome 9 was observed in 1 tumor. Chromosomes 4, 6, and X were never aneusomic. The percentage of monosomy 17 nuclei was 2 to 4 times the amount noted with the other autosomes for tumor and benign tissue. Computer analysis demonstrated that these signals contained twice the signal density and were significantly different (p < 0.0001) than the single diploid chromosome 17 signals. This result is consistent with homologous pairing of chromosome 17 in benign and neoplastic prostate tissue. Anomalies of chromosomes 8 and/or 7 were present in 14 of the 16 cases (88%) aneusomic by fluorescent in situ hybridization. High grade tumors were more likely to be aneuploid on fluorescent in situ hybridization (p < 0.001). Tumors with chromosome 8 aneusomies were of higher stage (p < 0.05). Fluorescent in situ hybridization is more sensitive than flow cytometry for the detection of aneusomy/aneuploidy. The prognostic relevance of these findings will require further investigation.
Aneuploidy↗
Natural history of prostatism: impact of urinary symptoms on quality of life in 2115 randomly selected community men.
OBJECTIVES: To assess the impact of urinary symptoms on health-related quality of life (QoL), including degree of bother, worry, interference with daily activities, psychological well-being, sexual function, and general health in a community-based cohort of men. METHODS: Eligible white men (n = 2115) aged 40 to 79 years who had not undergone previous prostate surgery or had prostate cancer were randomly selected from county residents. These subjects completed a questionnaire, which asked them about frequency and bother of urinary symptoms, interference with daily activities, psychological well-being, worry about urologic disease, sexual functioning, and general health. RESULTS: Men with moderate to severe voiding symptoms reported, on average, four to six times the degree of bother and interference with daily activities and twice the level of worry of men with mild symptoms. Nearly five times the degree of bother and interference was reported for those with mild than with no symptoms. A higher percentage of men with moderate to severe symptoms (26% to 33%) than mild symptoms (< 8%) reported limiting fluids before bed, travel, or driving 2 hours. Receiver operating characteristic curves support the recommended symptom index cutpoint for moderate symptoms (= 8) by differentiating men with and without bother, interference with daily living, or dissatisfaction with urinary condition. CONCLUSIONS: Moderate to severe urinary symptoms have a significant impact on men's lives in terms of degree of bother, worry, interference with daily living, and psychological well-being. The recommended cutpoint on symptom index differentiates men with and without decrement in health-related quality of life.
Activities of Daily Living↗
The natural history of prostatism: the effects of non-response bias.
BACKGROUND: In epidemiological studies, non-response may raise the question of generalizability to the target population. Most investigations have not been able to access data that could provide information about the potential impact of non-response bias. METHODS: A 55% response rate was realized at baseline for a prospective cohort investigation of the natural history of benign prostatic hyperplasia in Olmsted County, Minnesota, during 1989-1991 (the Olmsted County Study of Urinary Symptoms and Health Status Among Men). This prompted a preliminary study of potential non-response bias among full participants, partial participants and complete non-responders. The medical diagnostic index maintained by the Rochester Epidemiology Project was used to ascertain the prevalence of specific conditions in the 9 years prior to study inception. RESULTS: The age-adjusted period prevalence rate for benign prostatic hyperplasia (%) was 9.6 (95% confidence interval [CI]: 8.1-11.0) for full participants, 8.2 (95% CI: 5.8-10.6) for partial participants and 5.3 (95% CI: 3.6-6.9) for complete non-responders. Other urologic diagnoses followed the same pattern. However, age-adjusted prevalence rates for general medical examination history and major non-urologic morbidities were decidedly similar across response groups. CONCLUSIONS: These data suggest response may have been driven, in part, by concerns about urologic disease. However, the similarity in non-urologic diagnoses and general medical examinations provide some preliminary reassurance that the 55% response rate did not necessarily compromise generalizability.
Adult↗
Radical prostatectomy for clinically localized prostate cancer: long-term results of 1,143 patients from a single institution.
PURPOSE: To determine the efficacy and complication rate of radical prostatectomy (RP) as a treatment option for clinically localized prostate cancer (clinical stage < or = T2c). METHODS: The study was a retrospective analysis of 1,143 consecutive patients (median age, 64 years; range, 38 to 79 y) who underwent RP at one institution (mean follow-up time, 9.7 years). Complications for this study population were compared with those of a contemporary group of 1,000 consecutive patients. RESULTS: Of 1,143 patients, 83 (7%) had a low clinical stage (T1) and 160 (14%) had a low histologic grade (Gleason score < or = 3); 648 (57%) had a high clinical stage (T2b or T2c) and 204 (18%) had a high histologic grade (Gleason score > or = 7). Only 113 (10%) died of prostate cancer, and 177 (15%) developed metastasis. Adjuvant treatment (androgen deprivation or radiation therapy) was given in 197 (17%) patients (> or = pT3) and provided virtually identical results as without adjuvant treatment. The 10- and 15-year crude survival rates for 1,143 patients were 75% +/- 1.5% (SE) and 60% +/- 2.2%, respectively; the cause-specific survival rates were 90% +/- 1.1% and 83% +/- 1.9%, respectively; and the metastasis-free survival rates were 83% +/- 1.3% and 77% +/- 1.9%, respectively (398 men at risk at 10 years and 138 men at risk at 15 years). The 10-year survival rate for patients with Gleason score > or = 7 was 74% +/- 3.9%. Only tumor grade was a significant predictor for disease outcome. The hospital mortality rate decreased from 0.7% for the 1,143 study patients to 0% for the more recent 1,000 patients. Severe incontinence declined to 1.4% for the more recent 1,000 patients. Most patients who underwent RP were healthy (Charlson comorbidity index). CONCLUSION: Survival at 15 years was similar to the expected survival rate. Current morbidity and mortality rates associated with RP were extremely low. Thus, RP has been a viable management option for men with clinically localized prostate cancer who have a life expectancy of more than 10 years.
Adult↗