Deoxyribonucleic Acid Ploidy Research Articles

Some Small Prostate Cancers are Nondiploid by Nuclear Image Analysis: Correlation of Deoxyribonucleic Acid Ploidy Status and Pathological Features

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system§§Cell Analyses Systems, Elmhurst, Illinois.). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion.There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage Al, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p <0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc.We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.

Prognostic scoring in adult astrocytic tumors using patient age, histopathological grade, and DNA histogram type.

High-grade astrocytic tumors constitute the most serious as well as the most common group of primary brain tumors. Although several prognostic factors have been proposed, little is known about the prognostic value of deoxyribonucleic acid (DNA) ploidy in adult astrocytic tumors. In a series of 146 adult patients, aged 16 to 82 years, the individual prognostic values of six variables were studied, namely: tumor histopathological grade, treatment, patient age, extent of tumor, ploidy level, and DNA histogram type. Cox's proportional hazard model was then applied to the data to ascertain which factors might independently determine patient survival. Univariate analyses revealed that histopathological grade, age, and DNA histogram type were very powerful prognostic factors. The statistical significance of the influence of adjuvant radiotherapy and chemotherapy was at a borderline level, and the two remaining variables (tumor extent and ploidy level) had no prognostic relevance. Multivariate analyses showed that age, histopathological grade, and DNA histogram type were independent, statistically significant prognostic factors. A prognostic score was calculated from Cox's polynomial function in which those factors were introduced. The best score corresponded to a patient aged 16 years with a hypertriploid low-grade astrocytoma, while the worst score corresponded to a patient aged 82 years with a diploid high-grade astrocytoma. The worst score:best score ratio revealed a risk 71 times higher for a bad prognosis. It is concluded that patient age, histopathological grade, and DNA histogram type are very powerful prognostic factors for adult astrocytic tumors. A prognostic score including those factors could be used to characterize astrocytic tumor aggressiveness presurgically on fine-needle aspirates, and to monitor the patient's postsurgical evolution to define the appropriate therapy.

Prognostic Significance of Flow Cytometry Deoxyribonucleic Acid Analysis of Human Oligodendrogliomas

Flow cytometry was used to determine the deoxyribonucleic acid ploidy and proliferative activity of 60 oligodendrogliomas and oligoastrocytomas. The relationships among survival, ploidy, proliferation, histological features, and clinical variables were analyzed. Survival was strongly associated with the S-phase fraction (P < 0.001). Three groups with significantly different survival rates were defined, based on S-phase fraction ranges of < 3%, 3 to 5.9%, and > 6%. Significant associations between survival and age at diagnosis (P < 0.001), tumor grade (P < 0.001), and extent of surgery (P < 0.01) were found also. The poor correlation between mitotic figures and survival in oligodendrogliomas that has been reported previously emphasizes the need for an accurate method to measure proliferative activity. Our study demonstrated the usefulness of the flow cytometry-determined S-phase fraction in this regard and demonstrated that specific reference ranges could be defined for clinical application. In contrast, the determination of ploidy by flow cytometry was not useful in the evaluation of oligodendrogliomas.

The prognostic significance of DNA ploidy in clinically localized prostate cancer treated with radiation therapy

Purpose : To determine the prognostic significance of deoxyribonucleic acid (DNA) ploidy in comparison to pretreatment prostate specific antigen (PSA) and other prognostic factors for patients with adenocarcinoma of the prostate treated with external beam radiotherapy. Methods and Materials : Paraffin-embedded prostatic adenocarcinoma material was obtained from patients treated from 1987–1991. Sufficient histologic material for flow cytometric DNA content analysis was obtained from 86 patients and adequate histograms were obtained from 76 of these. The DNA histogram profiles were classified as diploid, tetraploid, or aneuploid. Median patient follow-up was 36 months. Results : There were 54 patients with diploid tumors, and 22 with nondiploid tumors (11 tetraploid and 11 aneuploid). Since the disease outcome for tetraploid and aneuploid tumors was the same, these were pooled (nondiploid tumors). The distribution of diploidy and nondiploidy correlated with pretreatment PSA ( p < 0.0005) and grade ( p = 0.055), but not with stage, pretreatment prostatic acid phosphatase, transurethral resection, pretreatment serum testosterone, or age. In actuarial univariate analyses, DNA ploidy was a significant predictor of outcome for local failure, distant metastases, any clinical relapse, rising PSA, and rising PSA and/or relapse. Ploidy was not a significant predictor of overall survival, although there were only six deaths. Diploidy predicted for improved outcome, for example, 34.6% incidence of a rising PSA and/or relapse at 4 years compared to 76.9% with nondiploidy ( p < 0.0001). An actuarial univariate analysis of other potential prognostic factors using the composite endpoint of rising PSA and/or relapse also revealed pretreatment PSA, grade, pretreatment prostatic acid phosphatase, stage, and serum testosterone to be significant predictors of outcome. In Cox proportional hazards analysis, pretreatment PSA, DNA ploidy, and grade were the only independent prognostic factors for disease outcome using the composite endpoint. Conclusion : DNA ploidy is an independent predictor of outcome in patients with Stages T,-T3 prostate cancer treated with definitive external beam radiotherapy.

Evaluation of deoxyribonucleic acid ploidy and S-phase fraction as prognostic parameters in advanced epithelial ovarian carcinoma: A prospective study

OBJECTIVE: Our goal was to study the prognostic value of deoxyribonucleic acid ploidy and S-phase fraction in advanced ovarian carcinoma. STUDY DESIGN: Prognostic factors for corrected survival were evaluated in a prospective study including 169 patients with stage III and IV ovarian cancer treated between 1985 and 1990. RESULTS: A total of 79% of the tumors were deoxyribonucleic acid aneuploid. Deoxyribonucleic acid aneuploidy was associated with grade of differentiation. S-phase fraction could be calculated in all deoxyribonucleic acid euploid tumors and 76% of the deoxyribonucleic acid aneuploid tumors. By multivariate analysis deoxyribonucleic acid ploidy, histologic type and grade, age, International Federation of Gynecology and Obstetrics stage, and amount of residual tumor were independent prognostic variables for corrected survival. On the basis of Cox regression a relative risk for the individual patient could be calculated. CONCLUSION: Deoxyribonucleic acid ploidy gives additive prognostic information and is a useful parameter for dividing patients with advanced ovarian cancer into risk groups for treatment decisions. (AM J OBSTET GYNECOL 1994;170:479-87.)

Deoxyribonucleic Acid Ploidy in Seminomas with and without Syncytiotrophoblastic Cells

Seminomas with human chorionic gonadotropin-producing syncytiotrophoblastic cells have been discussed as a distinctive subgroup with a worse prognosis. In a series of 50 seminomas (30 with immunohistochemically detectable syncytiotrophoblastic cells and 20 without syncytiotrophoblastic cells) deoxyribonucleic acid (DNA) ploidy was determined by flow cytometry in paraffin-embedded histopathological material. Comparatively, in 28 cases the DNA content was assessed by image cytometry on Feulgen-stained slides. DNA aneuploidy was detected in 49 seminomas (98%). No differences in the distribution of DNA index were observed between cases positive and negative for syncytiotrophoblastic cells (average DNA index 1.68 ± 0.44 for positive cases and 1.71 ± 0.52 for negative cases). Flow cytometry and image cytometry DNA index values showed a statistically significant correlation (p <0.01). Intra-tumoral heterogeneity of DNA content was found in 2 seminomas negative for syncytiotrophoblastic cells. Multiploidy and hypertetraploidy were noted more often in negative cases also. DNA ploidy or distinct aneuploid stemlines did not correlate with histopathological tumor stage or clinical course. The results favor the notion that the occurrence of syncytiotrophoblastic cells in seminomas represents only an example of intra-tumoral variability of tumor cell differentiation and does not justify the definition as a separate subgroup with distinct biological behavior.

Deoxyribonucleic Acid Content and Survival Rates of Patients with Transitional Cell Carcinoma of the Bladder

In 127 patients with urothelial carcinoma of the bladder the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Patients were followed for 1 to 9 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumor and clinical course. Tumors were histologically classified as grade 1—DNA frequency peaks in the diploid range, grade 2— heterogenous DNA distribution patterns, and grade 3—73% aneuploid and 27% tetraploid DNA values. The proliferation rate of the tumor cells was statistically greater in cases of histological grades 2 and 3 malignancy than in grade 1 malignancy.There was also a positive correlation between tumor stage and DNA ploidy. The cell lines were aneupolid in 38% of the patients with stage pTl, 64% with stage pT2 and almost 85% with stage pT3 tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell lines had no metastases and no local tumor progression for up to 9 years, whereas patients with multiple aneupolid tumor cell lines suffered recurrence and local tumor progression within 6 to 36 months. On the average, the patients died of the tumors 26 months after primary diagnosis. The difference in tumor recurrence and in tumor progression between patients with aneuploid and diploid tumors was highly significant (p<0.001).The prognosis for patients with grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy, although they exhibit the same degree of histomorphological differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive). In terms of multivariate Cox regression analysis, DNA ploidy compared with grade and tumor stage was the strongest predictor of survival.

Deoxyribonucleic acid analysis facilitates the pretreatment identification of high-risk endometrial cancer patients

Objective: Our purpose was to assess the proficiency with which cytometrically determined deoxyribonucleic acid variables from pretreatment curettage specimens identify patients at high risk for extrauterine disease or posttreatment relapse. Study Design: Flow cytometrically determined deoxyribonucleic acid ploidy, S-phase fraction, deoxyribonucleic acid index, and proliferative index were assessed in 140 paraffin-embedded curettage specimens containing endometrial carcinoma. Results: Although clinical staging identified only 19% of patients with advanced disease, 46% of surgical stages III and IV were aneuploid, 69% had an S-phase fraction ≥9%, and 69% had a prolferative index ≥14%. Documented recurrences and cancer-related deaths correlated with nondiploid patterns (29% of 140, 50% of recurrences, 54% of deaths), 5-phase fraction ≥ 9% (41 % of 140, 67% of recurrences, 75% of deaths), and proliferative index ≥ 14% (45% of 140, 73% of recurrences, 79% of deaths). Deoxyribonucleic acid index ( 1.5) provided additional stratification of aneuploid tumors ( p p Conclusion: Deoxyribonucleic acid ploidy and proliferative activity in pretreatment curettage specimens identified the majority of patients at high risk for extrauterine metastasis and relapses.

Deoxyribonucleic Acid Ploidy of Core Biopsies and Metastatic Lymph Nodes of Prostate Cancer Patients: Impact On Time to Progression

We studied 98 patients with locally confined but lymph node positive prostatic cancer (1 stage T1, 29 stage T2, 55 stage T3 and 2 stage T4) who were not treated by radical prostatectomy. A retrospective analysis was done of deoxyribonucleic acid (DNA) ploidy of pretreatment core biopsies of the primary tumor and lymph node metastases. While DNA ploidy has been shown to be an important prognostic factor if applied to radical prostatectomy specimens, core biopsy specimens and nodal metastases have rarely been studied. Of the 98 patients 87 were evaluable for DNA ploidy: 45 (52%) had diploid, 13 (15%) had tetraploid and 29 (33%) had aneuploid tumors. The ploidy of the primary tumor and of the lymph node metastases correlated significantly with the rate of progression and interval to progression. Also, significant correlations were noted between the percentages of cells in the S phase or S plus G2 phases of the cell cycle and interval to progression.Most patients in this study are part of the European Organization for Research and Treatment of Cancer protocol 30846, a prospective randomized study of early versus delayed treatment in lymph node positive, otherwise locally confined prostate cancer. This study is ongoing. Early endocrine treatment was associated with a significantly longer interval to progression. In a Cox regression analysis of the prognostic factors involved in this study, early endocrine treatment was more important than ploidy or proliferation patterns. Stage (T category) and histopathological grade did not show a correlation with progression. Followup is still too short and the numbers of patients are too small for relevant subgroup analysis.DNA ploidy measurement by flow cytometry on archival (paraffin embedded) core biopsy and lymph node material is possible, and produces meaningful results in predicting the prognosis of prostatic cancer. Since this information can be made available before treatment decisions, its exact value in the management of locally confined prostate cancer can be determined.

Prognostic significance of flow cytometry in non-small-cell lung cancer

To clarify the value of deoxyribonucleic acid (DNA) ploidy analysis, we prospectively studied single-parameter flow cytometric findings of fresh tissue from 272 patients with primary non-small-cell lung cancer from whom adequate tissue from the lung cancer was available. The mean age of the patients was 65.5 years; 65.8% were men. Histologic types were as follows: adenocarcinoma, 107 (39.3%); squamous cell, 100 (36.8%); large cell, 56 (20.6%); adenosquamous, 8 (2.9%); and giant cell, 1 (0.4%). Histologic grades were as follows: I (well differentiated), 15 (5.5%); II, 100 (36.8%); and III, 157 (57.7%). American Joint Committee on Cancer stages were as follows: I, 151 (55.5%); II, 38 (14%); III, 74 (27.2%); and IV, 9 (3.3%). Survivals at 1 year and 3 years were 74.2% +/- 2.8% and 52.4% +/- 4.8%, respectively. For non-squamous cell lung cancer, multivariate analyses with the Cox proportional hazards regression model for survival showed (1) that increasing American Joint Committee on Cancer stage (p < 0.001), male gender (p = 0.02), and histologic grades II and III (p = 0.04) were of independent (negative) prognostic significance and (2) that the presence and absence of DNA aneuploidy (p = 0.91), the classification of DNA histogram (p = 0.81), the DNA index (p = 0.46), and the results of cell cycle analysis in tumors with no aneuploidy (S phase, p = 0.23; S + G2M, p = 0.62) were of no prognostic significance. For squamous cell lung cancer, multivariate analyses showed that increasing American Joint Committee on Cancer stage (p = 0.003) and increasing DNA index (p = 0.009) were of independent (negative) prognostic significance.

Analysis of prognostic factors in stage I epithelial ovarian carcinoma: Importance of degree of differentiation and deoxyribonucleic acid ploidy in predicting relapse

Our purpose was to identify prognostic factors in stage I epithelial invasive ovarian carcinoma. The traditional clinical and pathologic prognostic variables and deoxyribonucleic acid ploidy were analyzed in a group of 290 patients. A multivariate analysis identified degree of differentiation as the most powerful prognostic indicator of disease-free survival, followed by deoxyribonucleic acid ploidy and, finally, International Federation of Gynecology and Obstetrics (1986) stage. Tumors with clear cell carcinoma elements were not graded, and in this subgroup International Federation of Gynecology and Obstetrics (1986) stage was the most important prognostic characteristic. When the effects of the three most important factors were accounted for in graded tumors, then none of the following were prognostic: histologic type, dense adhesion, extracapsular growth, ascites, rupture during surgery, International Federation of Gynecology and Obstetrics (1973) stage, size of tumor, and age and type of adjuvant treatment. None of 77 patients with well differentiated deoxyribonucleic acid diploid tumors had relapses. Deoxyribonucleic acid ploidy is an important new independent prognostic factor in stage I ovarian carcinoma.

Use of Fluorescent in Situ Hybridization for Deoxyribonucleic Acid Ploidy Analysis of Prostatic Adenocarcinoma

Fluorescent in situ hybridization using 2 chromosome specific centromere probes was evaluated as a method of ploidy analysis in touch preparations from 50 radical prostatectomy specimens. Tumors were classified as aneuploid by fluorescent in situ hybridization when nuclei had an abnormal copy number (aneusomic) for either chromosome centromere 8 or 12. Tetraploid tumors were defined as those with 4 copies (tetrasomic) of chromosome centromeres 8 and 12. The fluorescent in situ hybridization ploidy patterns were compared to the deoxyribonucleic acid (DNA) ploidy patterns subsequently obtained by flow cytometry on the same tissue following paraffin embedding. Concordant fluorescent in situ hybridization and flow cytometry ploidy classification was obtained in 82% of the cases (p ≦0.0001). Of 7 aneuploid tumors 3 were identified by both methods. Trisomy 8 was detected by fluorescent in situ hybridization in 3 cases that were classified as DNA diploid (2 tumors) and DNA tetraploid (1 tumor). Conversely, flow cytometry detected aneuploidy (hypotetraploidy) in 1 tumor when the fluorescent in situ hybridization results were consistent with tetraploidy. Overall, fluorescent in situ hybridization was more sensitive in aneuploidy detection (6 of 7 cases) than flow cytometry (4 of 7). Of 19 tetraploid cases 5 had discordant fluorescent in situ hybridization and flow cytometry results. However, all 5 cases contained low levels of tetraploidy and the discrepant results were most likely due to the limits of precision of 1 or both methods. In conclusion, we demonstrated that fluorescent in situ hybridization ploidy analysis can be rapidly performed on fresh touch preparations of prostate tissue. This preliminary study demonstrates that the ploidy result determined by fluorescent in situ hybridization correlates well with that obtained by flow cytometry. More complete fluorescent in situ hybridization studies of prostate carcinoma will require additional probes for other chromosomes.

Blood vessel invasion by tumor cells predicts recurrence in completely resected T1 N0 M0 non-small-cell lung cancer

The prognostic significance of traditional and newer tumor cell-related biologic parameters, like deoxyribonucleic acid ploidy (flow cytometry), proliferative activity (expression of proliferating cell nuclear antigen by immunohistochemistry), mitotic count, and intratumoral or peritumoral (or both) blood or lymphatic vessel invasion by tumor cells was investigated in 95 consecutive patients who had T1 N0 M0 non-small-cell lung cancer and who had operation alone between 1975 and 1985. The median follow-up for the entire group is now 8.3 years, and overall 5-, 10-, and 15-year-survivals were 75%, 69%, and 61%, respectively. Twenty-two patients died of either local (n = 3) or systemic (n = 19) recurrent non-small-cell lung cancer, 5 of non-cancer-related causes, 2 of new primary lung cancer, and 1 of an extrathoracic cancer. By multivariate analysis, blood vessel invasion by tumor cells (p = 0.0001) and mitotic count (p = 0.016) were independent predictors of survival; by contrast, the disease-free survival was influenced only by blood vessel invasion (p = 0.0004). The relative risk of death of recurrent non-small-cell lung cancer for low-risk patients (n = 79) was 13.3 (95% confidence interval, 6.1 to 28.7) times lower than that of high-risk patients (n = 16) (p < 0.0001). The relative risk of manifesting recurrent disease as distant metastasis for high-risk patients was 25.64 (95% confidence intervals, 8.4 to 77.6) times higher than that of their low-risk counterparts (p < 0.0001). These results provide a rationale for effective systemic adjuvant treatment in completely resected T1 N0 M0 non-small-cell lung cancer tailored to the individual patients' risk of development of recurrent non-small-cell lung cancer.

Is T factor of the TNM staging system a predominant prognostic factor in pathologic stage I non-small-cell lung cancer?: A multivariate prognostic factor analysis of 151 patients

We attempted to clarify whether the T factor of the TNM staging system should be viewed as a predominant prognostic factor in patients with pathologic stage I non-small-cell lung cancer when analyzed together with various histopathologic factors and deoxyribonucleic acid ploidy pattern of tumors. We studied 151 patients who were in this stage. Histopathologic factors used in the analysis were as follows: histologic cell type (squamous or nonsquamous cell carcinoma), grade of differentiation, and tumor invasion of visceral pleura and vessels. Deoxyribonucleic acid ploidy pattern of tumors was analyzed by flow cytometry, and the tumors were classified as diploid or aneuploid tumors. Significant prognostic factors (p < 0.05) that were demonstrated by univariate analysis of survival curves were as follows: (1) T1 versus T2; (2) well versus moderately or poorly differentiated tumor; (3) the absence versus presence of tumor exposed on pleura, (4) artery invasion, (5) lymphatic vessel invasion; and (6) diploid versus aneuploid tumor. Multivariate prognostic factor analysis showed the grade of differentiation and deoxyribonucleic acid ploidy pattern to be predominant prognostic factors. The T2 tumor group had significantly more cases with tumor invasion of lymphatic vessels that did the T1 tumor group and included 18 cases with tumor exposed on pleura. When these two factors were excluded from multivariate analysis, the T factor was marginally significant (p = 0.08). These observations suggest that the T factor is not necessarily a predominant prognostic factor in pathologic stage I non-small-cell lung cancer.

Analysis of solid renal dysplasia by flow cytometry: malignant potential?

Renal nodular blastema/nephroblastomatosis is a recognized precursor of Wilms tumor. It also has been shown that nodular renal blastemata are seen in association with dysplastic renal parenchyma secondary to obstructive uropathy (i.e., ureteroceles or ectopic ureters). In an attempt to improve our understanding of the critical relationship between renal dysplasia and neoplasia, we performed flow cytometric evaluation on 16 paraffinembedded specimens of dysplastic kidneys removed during the period 1984–1989. All nephrectomy specimens were associated with obstruction, either duplex collecting systems (10), ectopic ureters (2) or posterior urethral valves (2), or vesicoureteral reflux (2). One specimen was found to contain nodular renal blastema. No evidence of malignancy was found in any specimen. A specimen of normal kidney and two of Wilms tumor (favorable histology) were studied for comparison. Nuclear deoxyribonucleic acid (DNA) ploidy studies were performed on single dissociated nuclei after deparaffinization and staining with propidium iodide. All dysplastic specimens, including the specimen with nodular renal blastema, demonstrated a diploid pattern of DNA as did the specimens of normal renal tissue. The Wilms tumor specimens demonstrated a diploid and a tetraploid pattern. In view of the fact that Wilms tumor may demonstrate diploid DNA patterns on flow cytometry, the findings of diploid patterns on all specimens of solid dysplasia militate against but do not eliminate the possibility of malignant degeneration.

Deoxyribonucleic acid analysis facilitates the pretreatment identification of high-risk endometrial cancer patients

Our purpose was to assess the proficiency with which cytometrically determined deoxyribonucleic acid variables from pretreatment curettage specimens identify patients at high risk for extrauterine disease or posttreatment relapse. Flow cytometrically determined deoxyribonucleic acid ploidy, S-phase fraction, deoxyribonucleic acid index, and proliferative index were assessed in 140 paraffin-embedded curettage specimens containing endometrial carcinoma. Although clinical staging identified only 19% of patients with advanced disease, 46% of surgical stages III and IV were aneuploid, 69% had an S-phase fraction > or = 9%, and 69% had a proliferative index > or = 14%. Documented recurrences and cancer-related deaths correlated with nondiploid patterns (29% of 140, 50% of recurrences, 54% of deaths), S-phase fraction > or = 9% (41% of 140, 67% of recurrences, 75% of deaths), and proliferative index > or = 14% (45% of 140, 73% of recurrences, 79% of deaths). Deoxyribonucleic acid index (< 1.5 vs > 1.5) provided additional stratification of aneuploid tumors (p < 0.01). Multivariate analysis identified the proliferative index as the most cogent independent prognostic factor (p < 0.01). Deoxyribonucleic acid ploidy and proliferative activity in pretreatment curettage specimens identified the majority of patients at high risk for extrauterine metastasis and relapses.

Prognostic Significance of Bromodeoxyuridine High Labeled Bladder Cancer Measured by Flow Cytometry: Does Flow Cytometric Determination Predict the Prognosis of Patients with Transitional Cell Carcinoma of the Bladder

We studied whether flow cytometric determination of proliferative cell activity estimated by the bromodeoxyuridine in vitro labeling technique provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. We evaluated 81 patients with transitional cell carcinoma of the bladder using fresh bladder specimens. Clinical followup of at least more than 24 months was requested, with the mean followup being 37.9 ± 10.5 months. Tumor grade and stage were the histological prognostic parameters. Flow cytometric bivariate measurements of deoxyribonucleic acid (DNA) ploidy and bromodeoxyuridine labeled cell index were evaluated. Tumors with a bromodeoxyuridine labeled cell index of more than 10.7%, which was the value of the mean plus 2 times the standard deviation obtained in grade 1 bladder tumors, were designated as high bromodeoxyuridine labeled cell index tumors. A total of 51 patients with low bromodeoxyuridine labeled cell index tumors demonstrated a 98.0% 3-year actuarial survival rate estimated by the Kaplan-Meier method, compared to 42.9% for those with high index tumors. Multivariate survival analysis was performed with Cox’s proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Histological tumor grade was the single most important prognostic factor (risk ratio 13.2, p <0.05), with tumor stage being the second most important (risk ratio 9.2, p <0.05), followed by bromodeoxyuridine labeled cell index status (risk ratio 6.9, p <0.05). DNA ploidy status did not influence the clinical outcome. When grade 3 tumors were classified as low and/or high bromodeoxyuridine labeled cell index tumors, 3-year actuarial survival rates were 85.7% and 27.3%, respectively. These results indicate that DNA/bromodeoxyuridine bivariate analysis can be used as an effective adjunct to histological examination for prognostication and decision-making in treatment of bladder cancer patients.

Prostate Adenocarcinoma: An Image Analysis Technique for DNA Ploidy Determination

A new method for ploidy determination of prostate cancers is described. The assay, performed on tissue sections, combines deoxyribonucleic acid (DNA) ploidy analysis with a determination of the proliferation index. Also described is a ploidy study on tissues derived from a small group (24) of patients with prostate cancer. The study evaluated the prognostic significance of this type of ploidy analysis. The analysis was performed on Feulgenstained tissue sections derived from paraffin-embedded tissue, and the proliferation index was derived from tissue sections stained with antibody to proliferating cells nuclear antigen. The study reveals that this new ploidy analysis method can be used on small prostate cancer sections. In this study, patients with diploid cancers had a longer survival time than patients with aneuploid tumors.

Preoperative Androgen Deprivation Therapy: Artificial Lowering of Serum Prostate Specific Antigen without Downstaging the Tumor

We studied 22 patients with clinical stage B2 (T2c) or C (T3) prostate cancer who underwent androgen deprivation therapy before radical prostatectomy as part of a downstaging protocol (group 1). The concentration of serum prostate specific antigen (PSA) was determined before and at the conclusion of androgen deprivation therapy, just before the operation. For each group 1 patient a match patient who had not received preoperative endocrine therapy (group 2) was chosen. The age of the group 2 patients was similar to that of the group 1 patients. The clinical stage of disease and pretreatment tumor grade in group 2 were identical to the stage and grade in group 1, and the serum PSA value in group 2 was similar to that of group 1 before initiation of androgen deprivation therapy. In group 1 the median serum PSA concentration was 14.8ng./ml. (range 3.1 to 99) before endocrine therapy and 0.2ng./ml. (range 0.1 to 3.4) after hormonal treatment. Group 2 had a median level of 13.3ng./ml. (range 3.4 to 100). The median decrease in the serum PSA concentration for group 1 as a result of androgen deprivation therapy was 98.5%. The radical prostatectomy specimens from these 2 groups of similar patients had no difference with regard to maximal tumor dimension, pathological stage and deoxyribonucleic acid ploidy status. These findings indicate that serum PSA becomes an unreliable indicator of disease status after initiating preoperative androgen deprivation therapy and that preoperative androgen deprivation therapy has little or no benefit for decreasing the extent of tumor or pathological stage. The concept of downstaging is misleading and must be examined in a randomized clinical trial.

Malignant potential of aneuploid pancreatic endocrine tumours.

Evaluation of the malignant potential of pancreatic endocrine tumours is difficult by histological criteria alone. Nuclear deoxyribonucleic acid (DNA) cytometric analysis can provide significant prognostic and biological information in a number of solid human tumours. Thus, the DNA profiles and nuclear parameters of 39 patients with pancreatic endocrine tumours diagnosed from 1969 to 1989 were studied, using computerized video image analysis. Of the 39 patients with tumours, 27 cases did not have evidence of metastatic disease at the time of investigation. The majority of these (N = 21) showed a diploid profile. Five were aneuploid and one was tetraploid. In the 12 tumours that proved malignant, three had tissue of both primary tumour and the metastases analysed; six had material only from the primary tumour, although metastatic disease was established clinically; and another three only had tissue from the secondary tumour studied. The majority of the malignant cases were aneuploid (N = 7); three were diploid; one showed a diploid primary but an aneuploid secondary, and one showed a hyperdiploid pattern. The percentage of nuclei with a DNA content greater than 5N (5CER) did not seem to contribute further to the assessment nor did the means of the nuclear areas and shape factors. It appears that ploidy studies may be useful in predicting malignant potential of pancreatic endocrine tumours. There is a high rate of immunostaining for insulin by benign pancreatic endocrine tumours and this may be a useful adjunct to distinguish them from their malignant counterparts. However, there is no statistically significant correlation between the expression of various hormones and the DNA ploidy of tumour cells.