Analysis Of Deoxyribonucleic Acid Content Research Articles

Flow-cytometric analysis of deoxyribonucleic acid content in advanced ovarian carcinoma: Its importance in long-term survival

OBJECTIVE: Our purpose was to evaluate the importance of deoxyribonucleic acid content to long-term survival from advanced epithelial ovarian carcinoma. STUDY DESIGN: Clinical and pathologic prognostic factors, including deoxyribonucleic acid content measured by means of flow cytometry, were analyzed for 282 patients. RESULTS: In 80% of the patients, the deoxyribonucleic acid patterns were nondiploid. In univariate analysis stage ( p < 0.0001), residual disease ( p < 0.0001), deoxyribonucleic acid index ( p = 0.01), and deoxyribonucleic acid ploidy ( p = 0.02) significantly predicted progression-free survival. In multivariate analysis stage ( p < 0.001), residual tumor ( p = 0.001), deoxyribonucleic acid ploidy ( p = 0.02), and deoxyribonucleic acid index ( p = 0.02) retained independent prognostic value. Residual disease and deoxyribonucleic acid content retained independent prognostic value for stage III tumors but not for stage IV tumors. CONCLUSION: Deoxyribonucleic acid analysis with flow cytometry provides prognostic information about long-term progression-free survival from advanced ovarian carcinoma and should be considered in the stratification processes of patients in future clinical trials. This prognostic information appears to be inversely related to tumor burden. (Am J Obstet Gynecol 1996;175:1217-25.)

Deoxyribonucleic acid ploidy status as no basis for pathologic stage prediction in clinically resectable prostate cancer

Assessment of deoxyribonucleic acid (DNA) ploidy status of a tumor as a means for predicting pathologic stages in prostate cancer. DNA ploidy of each focus of a cancer in 70 radical prostatectomy specimens was determined by nuclear image analysis. DNA ploidy was compared with the pathologic features of tumors. One hundred three individual cancers in 70 patients were used for DNA ploidy analysis. Of these, 39 (38%) were diploid and 64 (62%), nondiploid. DNA ploidy was weakly correlated with increase in tumor volume (P = 0.049) but not tumor grade. The relationship between DNA content and extraprostatic spread was not statistically significant. Increase in tumor volume and grade promoted extraprostatic spread more than nondiploidy, as shown by multivariate analysis. The incidence of a nondiploid cell population in a tumor focus in prostate cancer is essentially the same, at least for Americans and Japanese. DNA ploidy of a tumor cannot serve as a means of pathologic stage prediction in clinically resectable prostate cancers, contrary to many previous studies. Thus, DNA content analysis would be of no use for deciding on the treatment strategy of prostate cancer.

Flow cytometric dna content analysis of paraffin-embedded tissue derived from cervical carcinoma

Purpose: Flow cytometric deoxyribonucleic acid (DNA) content analysis has been shown to be of prognostic importance in some cancers. There have been recent reports of a prognostic importance for DNA content analysis in cervical carcinoma. Methods and Materials: We retrospectively reviewed the hospital and radiation oncology records of cervical carcinoma patients who presented between 1984–1990. Results: A total of 101 archival paraffin-embedded blocks were processed, of which 77 were of technical quality for analysis. Thirty-five percent were found to be DNA content aneuploid (DNA-A) and 65% DNA content diploid (DNA-D). No statistical difference was found between the two groups in age at diagnosis, % S-phase, coefficient of variation (CV), or proliferative index (PI). A statistical difference was noted in the G 2M phase between the two groups ( p = 0.004). The median % S-phase was 8.4% in the DNA-D group. A statistical difference ( p = 0.017) in survival was noted between the low and high % S-phase DNA-D groups. In patients who received radiation alone, high-PI patients had improved survival compared to low-PI patients. No statistical difference in survival was noted in the high % S-phase DNA-D group and DNA-A group ( p = 0.28). Proportional Hazard (Cox) Regression found clinical stage the only independent prognostic indicator for survival. Conclusion: Flow cytometric DNA content analysis is being used more frequently in the management of different malignant tumors. Our study shows that DNA content analysis is useful in determining the prognosis and survival outcomes in cervical carcinomas and may aid in predicting outcome to certain types of treatment regimens.

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.

Cochlear cytogenesis visualized through pulse labeling of chick embryos in culture

Cytogenesis in the basilar papilla sensory epithelium of the chicken was investigated through pulse labeling of proliferative cells. Tritiated-thymidine was injected intravenously in chick embryos cultured in petri dishes. All embryos received the injection on the seventh day of incubation (E7), when the progenitors of hair cells and supporting cells are replicating deoxyribonucleic acid (DNA). Cells that were in the synthesis phase of the cell cycle, either at the time of the 3H-thymidine pulse or within 2 hours, incorporated detectable levels of the radioactive DNA precursor. Labeled cells were identified in cochleae from embryos fixed at 0.5, 1, 2, 4, 6, 12 hours, 6 and 8 days after the pulse. One hour after the injection the majority of labeled nuclei were in the basal and middle strata of the sensory epithelium. Four to 6 hours after the injection, a greater number of labeled cells appeared in the lumenal stratum. The patterns of labeled cells in embryos fixed immediately after the injection of 3H-thymidine and in others fixed 6 to 8 days after the injection were unchanged, suggesting that the progenitor cells divide and their progeny differentiate in the sensory epithelium without appreciable transverse migration. Mitotic figures were usually observed only in the lumenal stratum. Analysis of DNA content in the populations of Feulgen-stained nuclei at three levels of depth through the epithelium also produced results consistent with the conclusion that vertical nuclear migration occurs during development of the cells in this sensory epithelium.

Flow Cytometric Deoxyribonucleic Acid Analysis in Stage I Renal Cell Carcinoma

Tumor deoxyribonucleic acid (DNA) content was analyzed by flow cytometry in 60 consecutive patients with stage I renal cell carcinoma. Of 59 evaluable tumors 27 (46%) were homogeneously diploid, 1 (2%) was tetraploid and 31 (52%) were aneuploid. Of the 32 nondiploid tumors 25 were heterogeneous concerning ploidy. One of the 27 patients with diploid tumors had metastases compared to 5 of the 32 patients with nondiploid tumors (not significant). There was a significant difference in survival between patients with diploid and nondiploid tumors (p = 0.043). Neither nuclear grade, tumor cell type nor tumor size correlated with survival. Analysis of DNA content seems to predict survival significantly for patients with stage I renal cell carcinoma.

Flow Cytometry Study of Cytokeratin 18 Expression According to Tumor Grade and Deoxyribonucleic Acid Content in Human Bladder Tumors

Cytokeratin 18 expression in transitional cells of 76 bladder tumors (11 grade 1, 33 grade 2 and 32 grade 3) and 10 normal biopsies was quantified by flow cytometry after immunolabeling with the anti-cytokeratin 18 monoclonal antibody RGE 53. Combined cytometric analysis of deoxyribonucleic acid content and cytokeratin 18 expression was conducted. Of 76 tumor biopsies 38 had a unimodal deoxyribonucleic acid profile with a deoxyribonucleic acid index close to 1.0, while the other 38 showed a bimodal profile: 1 peak with an index of 1.0 and a second peak with an index of greater than 1.0. The 11 grade 1 tumors belonged to the first group, whereas 10 of the 33 grade 2 and 28 of the 32 grade 3 tumors belonged to the second group. Antibody RGE 53 reacted with 4 per cent of the normal bladder cells (umbrella cells), 14 ± 3 per cent of the cells from grade 1, 33 ± 8 per cent from grade 2 and 56 ± 10 per cent from grade 3 tumors. Analysis of cytokeratin 18 expression according to deoxyribonucleic acid content at the single cell level in tumors with a bimodal deoxyribonucleic acid profile showed that cytokeratin 18 was detected frequently in cells with a high deoxyribonucleic acid index but much less so in cells with an index of 1.0. Therefore, expression of cytokeratin 18 can be recognized as a marker of aggressiveness in bladder tumors, since it increases in parallel with tumor grade and cell deoxyribonucleic acid content.

Flow cytometric analysis of deoxyribonucleic acid content in the gastrointestinal tract

Flow cytometric analysis of deoxyribonucleic acid content in the gastrointestinal tract

DNA aneuploidy in ulcerative colitis.

The prevalence of deoxyribonucleic acid (DNA) aneuploidy in 297 samples from 38 patients with ulcerative colitis of varying duration was investigated by flow cytometry. In 12 patients colitis was complicated by the development of colorectal carcinoma: one had three synchronous carcinomas. Only four of 14 carcinomas were DNA aneuploid. Deoxyribonucleic acid aneuploidy occurred focally in the colorectal mucosa in the presence and absence of carcinoma: rates of aneuploidy (67% in cancer patients and 42% in non-cancer patients), were not significantly different (chi 2 = 1.0962, p = 0.295). A higher rate of DNA aneuploidy was found in dysplastic tissues (21%) compared with non-dysplastic tissues (15%), but again these differences did not reach statistical significance (chi 2 = 1.0747, p = 0.299). Deoxyribonucleic acid aneuploidy and dysplastic change occurred more often with increasing duration of ulcerative colitis (p less than 0.001, p less than 0.005 respectively). We conclude that flow cytometric analysis of cellular DNA content should not replace present morphological methods of assessment of premalignancy in ulcerative colitis, but may be a useful adjunct in the identification of abnormal mucosa.

Bizarre blue nevus: A case report with deoxyribonucleic acid content analysis

A case report of an unusual variant of blue nevus is presented. The lesion demonstrated striking cytologic atypia but lacked clinical and certain histologic features of malignancy. Similarities and differences between this lesion and atypical blue nevus and Spitz nevus are discussed. An analysis of the deoxyribonucleic acid levels in lesional cells was consistent with polyploidy. This supports the interpretation of the lesion as atypical but is not inconsistent with a benign diagnosis.

Flow cytometric analysis of deoxyribonucleic acid (DNA) content in adult leukemia.

Flow cytometric analysis of the bone marrow cellular DNA content was performed in 40 adult patients with acute leukemia. Twenty-eight had AML (29 previously untreated and 9 relapse) and 12 ALL (8 previously untreated and 4 relapse). For the whole series, the mean G1/0-phase compartment was 82 +/- 1.3%, the mean S-phase compartment 14 +/- 1%, and the mean G2 +M-phase compartment 4 +/- 0.7%. The percentage of cells in the S-phase had a positive correlation with the LDH level, but not with other parameters. Patients at relapse had significantly lower percentages of cells in the S-phase in AML and significantly higher in ALL. The changes of the S-phase size of the same patients at the first and relapse phases varied. Patients who obtained complete remission had significantly higher percent S phase than patients who did not. This difference was more significant in ALL. Percent cytoreduction had no correlation with the remission rate or S-phase size. Therefore, we analyzed changes of cells in the S-phase of patients with untreated AML during chemotherapy. The reduction rate of cells in the S-phase of patients who obtained complete remission was significantly higher than that of patients who did not.