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Objective: To evaluate the relationship between the nuclear DNA content and the tissue estrogen receptor (ER) level in patients with operable adenocarcinoma of the prostate., Method: Surgical specimens taken from 73 patients with clinically localized prostate cancer were studied. Tumor DNA ploidy pattern as measured by flow cytometry was correlated with the level of functional ER using the nuclear biopsy assay., Results: Forty-five percent of the tumors were DNA diploid, and 55% had an abnormal ploidy pattern (DNA tetraploid or DNA aneuploid). The ER level ranged from 0 to 6,475 fmol/mg DNA (mean 839 fmol/mg DNA). Twenty-two percent had no functional receptors. Marked association was noted between ER and nuclear DNA content. Seventy-five percent of the tumors with no ER had abnormal ploidy patterns. The mean receptor level for DNA diploid prostate cancer was 1,034 fmol/mg DNA versus 661 fmol/mg DNA for DNA nondiploid tumors (p < 0.008). An inverse correlation was found between ER values and histologic grade or pathologic stage. High-grade and high-stage tumors had lower levels of ER compared to low-grade and early-stage carcinomas., Conclusion: Our results demonstrate an association between ER values and variables that predict prognosis in prostate cancer. It is possible that this parameter may be helpful in identification of prognostic groups in patients with prostate cancer.

Objective: To evaluate the impact of nuclear DNA content on outcome of patients with testicular seminoma., Methods: Formalin-fixed paraffin-embedded blocks taken from 111 patients with primary testicular seminoma were studied by flow cytometry for nuclear DNA content. The results of ploidy status were correlated with histopathologic features, tumor progression and patients' survival., Results: 48% of the tumors were DNA diploid and 52% were DNA aneuploid. None of the patients with DNA diploid seminoma had an advanced stage seminoma at the time of diagnosis. Progression after therapy or cancer-related death occurred only in patients who had DNA aneuploid testicular tumors., Conclusions: Nuclear DNA ploidy pattern provides important prognostic information for patients with testicular seminoma.

Eccrine poroma is a benign, slow growing, solitary adnexal tumor. Malignant degeneration may take place in longstanding solitary lesions; in such cases cutaneous and fatal visceral metastases have occurred. Our goal was to determine whether flow cytometry yields useful diagnostic and prognostic information on benign and malignant eccrine poroma. Flow cytometric analysis of the nuclear DNA ploidy pattern was performed on four samples of eccrine poroma and five samples of malignant eccrine poroma. All the histograms of the eccrine poromas were diploid. Two of five specimens (40%) of the eccrine porocarcinoma were aneuploid, and the other three (60%) were diploid. The diploid pattern represents another expression of the benignancy of eccrine poroma. Since abnormal DNA content is often correlated with tumor grade, the aneuploid DNA histogram of 40% of the patients with malignant eccrine poroma is not a surprising finding in this cytologically malignant neoplasm.

Objective: To assess the role of DNA ploidy as a predictor of radioresistance in T1 glottic carcinoma., Design: Case-control study. Flow cytometric DNA ploidy measurements were performed on formalin-fixed paraffin-embedded tumor specimens from 15 patients with T1 glottic laryngeal carcinomas in whom radiotherapy had failed and from a matched group of 15 patients in whom an identical radiotherapy regimen was curative. Analysis of DNA content was performed blind to outcome of treatment., Setting: Academic tertiary referral medical center., Participants: Thirty patients with clinically staged T1, N0, M0 glottic carcinoma., Intervention: All patients received radiation to the larynx through opposed lateral ports at a total dose of 64 to 70 Gy., Results: Ten diploid and five aneuploid histograms were found in the resistant group, and six diploid and nine aneuploid histograms were found in the radiosensitive group. This difference was not statistically significant. A trend toward a higher relapse rate after radiotherapy (62.5%) among patients with diploid tumor compared with those with aneuploid tumor (35.7%) was noted., Conclusions: DNA ploidy did not predict response to radiotherapy in patients with T1 glottic cancer, probably because of the small number of patients. A trend toward lower risk of local recurrence after radiotherapy in aneuploid tumors was noted. A larger prospective study is needed to assess the value of DNA ploidy in the treatment of early laryngeal cancer.

Purpose: We evaluated the clinical significance of deoxyribonucleic acid (DNA) ploidy pattern as a predictor of prognosis in patients with testicular seminoma., Materials and Methods: Flow cytometric nuclear DNA analysis was performed on archival specimens from 65 patients with pure seminoma who underwent radical orchiectomy between 1970 and 1992., Results: A total of 42 specimens (65%) exhibited a DNA diploid pattern, while 23 (35%) were DNA aneuploid. Diploidy was manifested in 73% of the stage I tumors versus 31% of stage II cancers (p = 0.004). No correlation was found between ploidy and histological type, size or local extension of the tumor. Tumor progression was observed in 5 patients, exclusively displaying aneuploid histograms (p = 0.0017), and 3 of them subsequently died of the disease., Conclusions: DNA ploidy pattern may provide important prognostic information for patients with testicular seminoma.

Background: The course of patients with renal cell carcinoma may be considerably different. Approximately 50% with presumed localized disease have metastases after nephrectomy. Pathologic stage at diagnosis, histologic grade, and histologic type have been considered the most important predictors of prognosis. Nevertheless, subsets of patients within a specified stage and grade may have considerable differences in disease progression and survival., Methods: Flow cytometric nuclear DNA analysis was used to study pathologic Stage I or II renal cell carcinoma in 54 patients who underwent radical nephrectomy between 1974 and 1983., Results: Sixty-three percent of the tumors were diploid, and 37% aneuploid. A DNA diploid pattern was more common among Stage I tumors than Stage II tumors (69% versus 33%; P < 0.04). Progression occurred in 31% of the diploid tumors, whereas among the aneuploid group the progression rate reached 59% (P < 0.06). Considered as a single indicator, DNA ploidy pattern was strongly associated with patient survival. Ten years after surgery 79% of the patients who had diploid tumors and 50% of those with aneuploid tumors were alive (P < 0.02)., Conclusions: Nuclear DNA ploidy may serve as an important prognostic variable for patients with early stage renal cell carcinoma.

The best treatment of patients with clinical Stage I nonseminomatous germ cell testicular tumors (NSGCTT) remains controversial. Archival formalin-fixed paraffin-embedded testicular tumor specimens from 23 patients diagnosed between 1977 and 1988 were available for analysis. All patients had clinical Stage I NSGCTT, and the specimens were prepared using Hedley's technique and propidium iodide staining prior to flow cytometric ploidy analysis. Tumors from 3 patients (13%) were classified as DNA diploid; the remaining 20 tumors had DNA aneuploid patterns. Eleven patients had retroperitoneal lymph node dissection (RPLND); 2 (18%) were upstaged to pathologic NSGCTT Stage IIA, and 1 had a subsequent relapse in the contralateral testicle. Among 12 patients in the surveillance protocols, 3 (25%) had tumor recurrence. All patients who were either upstaged to pathologic NSGCTT Stage IIA or had tumor recurrence while under surveillance had DNA aneuploid patterns. The 3 patients with DNA diploid tumor patterns had been in the surveillance protocols. To date, with fifteen months minimum follow-up, none has had tumor recurrence. Such data suggest that flow cytometric DNA ploidy analysis, when used as an adjuvant to more traditional prognostic parameters, may help to identify a group of patients with clinical Stage I NSGCTT at very low risk for recurrence and perhaps well-suited for surveillance management.

Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960-1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma.

Flow cytometric nuclear DNA analysis was performed on paraffin-embedded tissue samples taken from 184 patients with pheochromocytoma and paraganglioma treated between 1960 and 1987. The Hedley technique was used for measurement of nuclear DNA content. Thirty-five percent of the tumors were DNA diploid, 33% showed a DNA tetraploid pattern, and 32% had DNA aneuploid pattern. Familial pheochromocytoma and associated endocrine or neoplastic disorders were more common among patients with DNA nondiploid tumors. Eighty-four percent of the tumors that invaded blood vessels and all patients with regional or distant metastases had tumors classified as DNA tetraploid or DNA aneuploid. Of 22 patients who had disease progression, 21 (95%) had tumors with abnormal DNA ploidy pattern (P less than 0.001). All 12 patients who died of cancer-related disease had abnormal DNA ploidy; none of the patients with DNA diploid tumor (n = 64) have died of pheochromocytoma (P less than 0.01). These results suggest that nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pheochromocytoma and paraganglioma.

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.

A total of 71 patients with prostate carcinoma who underwent radical retropubic prostatectomy had preoperative measurement of serum prostate specific antigen levels and subsequent nuclear deoxyribonucleic acid ploidy analysis of the resected tumors. Prostate specific antigen levels were determined by a commercially available prostate specific antigen radioimmunometric assay (normal range 0 to 4.0 ng./ml.). The paraffin-embedded blocks of the prostate specimens were analyzed by flow cytometry for nuclear deoxyribonucleic acid content using Hedley's technique and propidium iodide staining. A strong association was found between nuclear deoxyribonucleic acid ploidy patterns and preoperative prostate specific antigen values. All patients with tetraploid and aneuploid tumors had elevated preoperative prostate specific antigen values. By contrast, all patients with preoperative antigen values of less than 4 ng./ml. had diploid tumors (p less than 0.0034). Prostate specific antigen levels were proportional to the estimated volume of the primary tumor (p less than 0.0065). However, even after statistical adjustment for tumor volume the preoperative prostate specific antigen value was still significantly and independently correlated with deoxyribonucleic acid ploidy pattern (p less than 0.007). However, only 35% of the patients with diploid tumors had antigen levels within the normal range. Conversely, 65% of the patients with diploid neoplasms had abnormally high antigen levels preoperatively. These results suggest that patients with localized biopsy proved prostate carcinoma and normal preoperative prostate specific antigen values are most likely to have diploid tumors; based on a 95% confidence level, the true proportion of patients with normal prostate specific antigen values who also have a deoxyribonucleic acid diploid tumor is 85 to 100%. Since localized deoxyribonucleic acid diploid tumors are known to be associated with a favorable prognosis for patients with prostate carcinoma treated by radical prostatectomy, a preoperative serum prostate specific antigen level within the normal range may help to predict disease outcome.

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.

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.

Flow cytometric analysis of nuclear deoxyribonucleic acid content was performed on 76 primary squamous cell bladder carcinomas treated between January 1970 and December 1975. Patients were followed for a median of 10.1 years. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 76 tumors 73 were evaluable by flow cytometry providing high quality deoxyribonucleic acid histograms: 27 (37 per cent) showed a deoxyribonucleic acid diploid or normal pattern, 17 (23 per cent) exhibited a significant increase in the 4C peak (deoxyribonucleic acid tetraploid) and 29 (40 per cent) showed a distinct aneuploid peak. High grade (grades 3 and 4) and high stage (stages T2 to T4) tumors had a significantly higher incidence of abnormal (either tetraploid or aneuploid) deoxyribonucleic acid patterns than low grade (grades 1 and 2) and low stage (stages Tis/Ta/T1) tumors (p less than 0.005). The 5 and 10-year rate free of disease for patients with deoxyribonucleic acid diploid tumors was 67 per cent compared to 22 and 18 per cent, respectively, for patients with tumors showing abnormal ploidy patterns (p less than 0.0005). At 5 and 10 years after diagnosis an estimated 18 per cent of the patients with deoxyribonucleic acid diploid tumors will die of bladder cancer. In contrast, an estimated 53 per cent of the patients with tetraploid tumors and 82 per cent and 86 per cent of those with aneuploid tumors will die of squamous cell bladder carcinoma by 5 and 10 years after diagnosis (p less than 0.0001). These results demonstrate that nuclear deoxyribonucleic ploidy measured by flow cytometry is an important objective prognostic variable for patients with squamous cell carcinoma of the bladder.

Flow cytometric nuclear DNA ploidy analysis was used to study pathologic stage C prostatic adenocarcinoma (pT3, N0, M0) in 146 patients who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between 1967 and 1981. Of these tumors, 46% had a DNA diploid pattern, 47% had a DNA tetraploid pattern, and 7% had a DNA aneuploid pattern. Abnormal ploidy patterns were associated more frequently with histologic high-grade tumors than with low-grade tumors. Considered alone, DNA ploidy pattern showed a strong association with subsequent prognosis. The median interval to progression for tumors with DNA tetraploid and DNA aneuploid patterns was 7.8 and 3.5 years, respectively. For the DNA diploid tumors, only 23% progressed within 18 years, the longest follow-up. At 10 years, only 10% of patients with DNA diploid tumors had died of prostatic cancer, in comparison with 28% of the DNA tetraploid and 36% of the DNA aneuploid groups (P less than 0.01). By analysis of a combination of histologic tumor grade and nuclear DNA ploidy pattern, an even stronger association with prognosis was demonstrated. For the 38 patients with histologic low-grade and DNA diploid tumors, progression-free survival was 92% at 10 years, in comparison with 57% for 23 patients with low-grade DNA nondiploid tumors. Patients with high-grade tumor had a poorer prognosis whether the DNA ploidy pattern was diploid or nondiploid. Nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pathologic stage C prostatic cancer treated by radical prostatectomy.