DNA content/ploidy as prognostic factors in prostate cancer.
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DNA, Neoplasm↗
Biomedical subjects
M M Lieber
Publications and source records attributed to M M Lieber.
DNA ploidy of ovarian dysgerminomas: correlation with clinical outcome.
Abnormal nuclear DNA content, as determined by flow cytometry, when combined with conventional prognostic variables such as tumor grade or stage at diagnosis, appears to identify patients who are at increased risk for recurrence of disease. The DNA content of ovarian dysgerminoma, a tumor that is homologous to testicular seminoma and is found in young women of childbearing age, was studied to determine if there is a correlation between DNA content and outcome. Such information would be useful in selecting treatment regimens and making possible the preservation of childbearing potential in women who are likely to have a good outcome. The specimens from 23 cases of ovarian dysgerminoma seen at our institution between 1950 and 1985 were analyzed by DNA flow cytometry. Five of the tumors were diploid (21%) and nineteen were nondiploid (79%). Patient outcome was not predicted any better by nuclear DNA content than by conventional prognostic variables.
Adult↗
Validation of a new quality of life questionnaire for benign prostatic hyperplasia.
In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted.
Adult↗
Nuclear deoxyribonucleic acid content measured by static cytometry: important prognostic association for patients with clinically localized prostate carcinoma treated by external beam radiotherapy.
To determine if relative nuclear deoxyribonucleic acid (DNA) content is an important prognostic parameter for patients with clinically localized prostate carcinoma treated by external beam radiotherapy, we performed static DNA cytometry on archival paraffin embedded prostate needle biopsy specimens obtained before treatment. DNA content was measured with the Zeiss IBAS 2000 Image Analyzer and the Feulgen staining method. Tumor samples from 65 patients with clinically localized carcinoma of the prostate treated with at least 6,000 cGy. from 1974 to 1980 were studied. Patients and tumors were divided into 2 groups: group 1 - 31 patients with relative DNA content less than 1.5 times normal and group 2 - 34 patients with relative DNA content greater than 1.5 times normal. The prostate cancer nonprogression rate at 10 years was 64% for group 1 and 11% for group 2. Prostate cancer cause specific survival at 10 years was 73% for group 1 and 20% for group 2. These differences are highly significant (p less than 0.0001). By contrast, stratification and analysis according to tumor clinical stage, Mayo histological nuclear grade or Gleason score proved not to be as significant. Cox multivariate analysis also identified DNA content as the most important independent variable for cancer specific survival and progression. Nuclear DNA content measured by static cytometry appears useful in identifying those patients with clinically localized prostate carcinoma who may have a favorable probability of long-term disease control by external beam radiotherapy.
Aged↗
Hormonal treatment at time of radical retropubic prostatectomy for stage D1 prostate cancer: results of long-term followup.
In this long-term study with a median followup of greater than 10 years 62 patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for stage D1 adenocarcinoma of the prostate were subdivided with respect to nuclear deoxyribonucleic acid ploidy status of the primary cancer and according to whether they received adjuvant early antiandrogen therapy. Patients with diploid cancers who underwent the operation and received adjuvant early endocrine therapy did significantly better than a similar group without early endocrine therapy with respect to disease-free survival (p less than 0.001) and survival from prostate cancer death (p = 0.03). Among patients with nondiploid tumors early endocrine therapy was of some benefit for disease-free survival (p = 0.06) but not for prostate cancer death (p = 0.46).
Adenocarcinoma↗
A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy.
In a prospective, randomized study, continuous infusion of epidural fentanyl citrate (group E) was compared with patient-controlled intravenously administered morphine sulfate (group P) for analgesia in 66 men after radical retropubic prostatectomy. Although both methods provided satisfactory analgesia, the mean comfort level scores were lower (that is, greater comfort) in group E than in group P at all observation times. The difference in mean resting comfort level scores between groups E and P was statistically significant (P < or = 0.05) at 9 of the 11 observation times. In addition, significant differences in comfort level scores were noted at 8 of the 11 observation times during deep breathing, 5 of 11 during coughing, and 3 of 9 during ambulation. Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower (that is, less pain) in group E than in group P for all four categories of activity. The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing. No significant differences were noted in side effect profiles or duration of hospital stay. In summary, when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospectively, patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine, as evidenced by lower mean, maximal, and minimal comfort level scores and a greater proportion of patients with complete relief of pain.
Aged↗
Effect of external beam radiotherapy on prostatic carcinoma DNA content as measured by static image cytometry.
Static image cytometry was used to study the effect of radiotherapy on the DNA content of prostatic carcinoma. Feulgen-stained specimens from 50 patients before and after radiotherapy were examined. The DNA index increased significantly after treatment (p less than 0.03), and it occurred equally in those with low (less than 1.5) and high (greater than or equal to 1.5) indices. The level of the initial DNA index was significantly related to the rate of symptomatic progression (p less than 0.05). The initial change in and final DNA indices were not related to survival however. There was a significant increase in Gleason score (p = 0.001) and histological grade (p = 0.01) after irradiation and, when taken individually, the degree of change was related to survival in both, p = 0.05 and 0.004, respectively. As Gleason score, Mayo grade and clinical stage were not independent variables; none of them was related to survival when corrected for the other factors. Thus, DNA content or ploidy, as well as Mayo grade and Gleason score, increases in recurrent tumor after radiotherapy. This may be of importance when considering what treatment to use and how intensively the patients should be followed up.
Actuarial Analysis↗
The prognostic significance of DNA ploidy pattern in transitional cell cancer of the renal pelvis and ureter: continuing follow-up.
Among 190 patients operated on for transitional cell cancer of the renal pelvis and/or ureter from 1976 to 1990, 95 had their tumor studied by flow cytometry. Of these, the prognostic significance of the DNA ploidy pattern with respect to the standard pathologic features was assessed in a retrospective analysis, where survival information were updated to October 1991 and the mean follow-up of patients exceeded 5.5 years (longest follow-up: 15.5 years). Five and ten-year survival probabilities for the whole group were, respectively, 65.5 and 51%. Patients with a diploid tumor had significantly better survival rates than patients with tetraploid/aneuploid cancer (p less than 0.00001). The impact of the DNA ploidy on survival was confirmed by a multivariate analysis of prognostic factors, where only tumor grade (p less than 0.0001), tumor stage (p less than 0.0001), number of neoplastic foci (p = 0.022) and nuclear DNA pattern (p less than 0.068) had a significant influence on survival. In the group of patients with low-stage (pTa-pT1) and low-grade (G1-G2) transitional cell cancer of the upper urinary tract, the DNA analysis was unable to identify any subset of patients at higher risk for disease progression.
Carcinoma, Transitional Cell↗
Treatment of primary squamous cell carcinoma of the upper urinary tract.
Forty-six patients with primary squamous cell carcinoma of the upper urinary tract treated over a 44-year period were studied. The lack of characteristic presentation caused delay in diagnosis. Associated urinary calculi were found in only five (11%) of the patients. Almost all of the tumors were histologically high grade; at surgery, 84% of the tumors were locally advanced or metastatic. Prognosis is poor independent of treatment; the overall 24-month survival rate was 22%. Comparison with a previous study of renal pelvic transitional cell carcinoma indicates that these two forms of urothelial neoplasm are biologically different.
Adult↗
Urinary symptom and quality of life questions indicative of obstructive benign prostatic hyperplasia. Results of a pilot study.
In a pilot study of a urinary symptom and health-related quality-of-life questionnaire for benign prostatic hyperplasia (BPH), responses from 64 Mayo Clinic patients with cystoscopic evidence of obstructive BPH were compared with those of 14 men with no cystoscopic evidence of BPH and a community sample of 64 comparably aged men with no medical history of prostate enlargement. Questions which best discriminated between the groups were those dealing with urinary symptom frequency, bother due to urinary symptoms, and worry and concern about urinary problems. The results suggest that urinary-symptom-bother and worry due to urinary symptoms may be important additions to the more usual questions asked about urinary frequency in the identification of men with BPH. These findings are preliminary, however, and will be verified in an ongoing natural history study of BPH.
Humans↗
Adenocarcinoma of the prostate involving 2 cell types (prostate specific antigen producing and carcinoembryonic antigen producing) with selective metastatic spread.
Of 3 patients with clinically localized adenocarcinoma of the prostate 2 were treated by radical prostatectomy and 1 was treated with radiation therapy. Serum prostate specific antigen (PSA) values were elevated before therapy. After treatment the PSA levels were decreased to zero. All 3 patients later had evidence of metastatic tumor spread to the liver with elevation of serum carcinoembryonic antigen but not PSA. Immunohistochemical staining of the 2 primary tumors from the prostatectomy specimens identified 2 cell clones, one immunoreactive to PSA and prostatic acid phosphatase (PAP) and nonimmunoreactive to carcinoembryonic antigen, and the other immunoreactive to carcinoembryonic antigen but not PSA or PAP. Biopsy of a hepatic metastasis in 2 patients confirmed anaplastic carcinoma of the carcinoembryonic antigen-producing cell type. Immunohistochemical staining of a lymph node metastasis identified the PSA-producing cell type only. Such results suggest selective metastatic spread of each cell type to its own organ tropic site. Occasional carcinoembryonic antigen-producing prostate cancers may metastasize to the liver. Serum carcinoembryonic antigen measurements occasionally may be useful in the management of certain prostate adenocarcinoma patients.
Adenocarcinoma↗
Transitional cell carcinoma of the upper urinary tract: evaluation of prognostic factors by histopathology and flow cytometric analysis.
Prognostic factors in transitional cell carcinoma of the upper urinary tract were assessed with histopathological examination and flow cytometric analysis in a series of 127 patients operated upon between 1976 and 1988. In particular, we evaluated the usefulness of flow cytometry to identify patients who require adjuvant treatment among those with low grade and low stage disease (51% in this series). A multivariate analysis was done on 92 cases, considering patient age and sex, stage, grade and number of lesions (unifocal versus multifocal), site (renal pelvis versus ureter), presence of vesical tumors, recurrences along the urinary tract or in the bladder, type of operation and nuclear deoxyribonucleic acid (DNA) ploidy (diploid versus tetraploid/aneuploid tumors). Only the stage (p = 0.001), grade (p = 0.001) and, to a lesser extent, the DNA pattern (p = 0.031), as well as the number of lesions (p = 0.061) were determinant for prognosis. In regard to the subgroup of 41 patients with grade 2 or less, stage P1 or less tumors, no significant difference in survival was demonstrated between diploid and nondiploid tumor patients. However, 7 of 10 patients from the latter group are still under observation. Therefore, our conclusions may have to be modified in the future.
Adult↗
Congenital cystic disease of the seminal vesicle.
Thirteen cases of congenital seminal vesicle cysts with pathologic correlation were diagnosed between 1970 and 1988. Twelve of the 13 patients had ipsilateral renal anomalies. Intravenous urography, performed in 11 of the 13 patients, demonstrated associated renal anomalies. Computed tomography, performed in nine of the 13 patients, demonstrated associated renal anomalies and displayed the cystic seminal vesicles. Transabdominal or endorectal ultrasonography, performed in eight patients, allowed characterization of the seminal vesicle masses as cystic. Magnetic resonance imaging, performed in three of the 13 patients, accurately demonstrated dilated ejaculatory ducts into which ectopic ureters inserted. The fluid in the seminal vesicle cysts had an increased signal intensity on T1- and T2-weighted sequences. Seminal vesiculographic study demonstrated anomalous communications with the seminal tract. Cystic disease of the seminal vesicles can be either congenital or acquired; congenital cysts are associated with anomalies of the ipsilateral mesonephric duct.
Adult↗
Prognostic importance of nuclear DNA content measured by flow cytometry for patients with adenocarcinoma of the prostate.
In 1990, nuclear DNA ploidy analysis for prostate cancer is no longer a research investigation. It is now a routine economical clinical test. Ploidy analysis, carried out by either flow or static cytometry, provides unique prognostic information which is not replaceable by standard clinical variables such as tumor stage, histologic grade, or tumor volume. My colleagues and I at the Mayo Clinic routinely utilize ploidy information on radical prostatectomy specimens to guide in the selection of adjuvant therapy for patients treated by this type of surgery and to help gauge their prognosis. We believe that rational management of patients with all stages of prostate carcinoma now requires knowledge of each individual tumor's ploidy pattern.
Adenocarcinoma↗
Flow cytometric DNA histograms of paraffin-embedded pheochromocytomas.
We proposed a new classification of pheochromocytomas according to DNA ploidy patterns. Proliferation index (PI = S% + 4C%) might be an alternative to 4C% which was used as a critical marker of DNA nonaneuploid histograms. The follow-up survey revealed that DNA tetraploid with minimum increase of PI could not rule out the substantial possibility of malignancy and the comparison of DNA diploid histograms disclosed that 22 and 0% showed significant increase of the ratio of 4C% to S% under PI and 4C% criteria, respectively. In conclusion, 4C% was more effective and reliable than PI in order to classify DNA nonaneuploid pheochromocytomas.
Adrenal Gland Neoplasms↗
The role of nuclear DNA ploidy in the prognosis and management of patients with prostate cancer.
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Cell Nucleus↗
Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis.
Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10 (4%). The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer.
Adenocarcinoma↗
Squamous cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.
From 1944 to 1987, 28 patients with squamous cell carcinoma of the upper urinary tract were treated and also had tumor specimens that were fully evaluable by flow cytometric nuclear deoxyribonucleic acid ploidy analysis: 22 had squamous cell carcinoma of the intrarenal collecting system, 4 had tumors of the ureter, and 2 had tumors of the renal pelvis and ureter. Eight patients (29%) had deoxyribonucleic acid diploid, 11 (39%) tetraploid and 9 (32%) aneuploid ploidy patterns. Ploidy pattern significantly correlated with histological grade and tumor stage. Almost all tumors were histologically of high grade; among the patients with high grade tumors ploidy analysis separated fair and poor prognosis groups. Pathological stage was the dominant clinical variable. A total of 14 patients (50%) had advanced stage disease and all died within 12 months of diagnosis. Nearly all of these patients showed abnormal ploidy patterns and ploidy analysis was not useful prognostically for this group. In contrast, all 3 patients with squamous cell carcinoma of the renal pelvis who were long-term survivors had deoxyribonucleic acid diploid tumors. However, there is no clear statistical evidence from this study that ploidy analysis provides important prognostic information independent of stage and grade for patients with squamous cell carcinoma of the renal pelvis.
Adult↗