Deoxyribonucleic Acid Aneuploidy Research Articles

DNA aneuploidy as a topographic malignant transformation pattern in a pleomorphic adenoma of long-term evolution: a case report

IntroductionWe present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas.Case presentationWe extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67.ConclusionThese findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique.

Deoxyribonucleic acid ploidy in endometrial carcinoma: a reproducible and valid prognostic marker in a routine diagnostic setting

The objective of the study was to investigate the prognostic impact of deoxyribonucleic acid (DNA) ploidy in endometrial carcinoma in a routine diagnostic series as compared with a research series. We studied a population-based series of 363 endometrial carcinomas prospectively collected, with long and complete follow-up. The prognostic value of DNA ploidy was investigated in a routine diagnostic series (n=262) and compared with the results from a previous research series (n=101). The proportion of DNA aneuploid tumors was 21% in the research series and 25% in the routine diagnostic series (P=NS). In both series, DNA aneuploidy was significantly correlated to higher age at diagnosis, nonendometrioid subtype, and high histologic grade. Patients with DNA aneuploid tumors had significantly poorer survival, adjusted for established clinicopathologic prognostic factors. DNA ploidy estimation in endometrial carcinoma adds independent prognostic information in a routine diagnostic setting.

DNA ploidy, proliferative activities, and immunophenotype of malignant lymphoma: application of flow cytometry.

To explore the flow cytometric diagnosis of malignant lymphoma, we examined the deoxyribonucleic acid (DNA) ploidy, proliferative activities, and immunophenotype of surgical biopsy- and fine-needle aspiration (FNA)-derived materials. Our goal was to determine the possibility of making a diagnosis of malignant lymphoma by flow cytometric analysis of FNA-derived materials. The DNA ploidy and proliferative indices including the percentage of S-phase fraction (SPF), G2 + M fraction (G2M), and Ki-67-positive fraction (Ki-67) were analyzed on the fresh materials from 84 consecutive patients with suspected malignant lymphoma. Flow cytometric analysis of surface antigens was simultaneously performed. Fourteen of the patients underwent FNA and subsequent surgical biopsy of the same lymph nodes for flow cytometric analysis. The proliferative indices of intermediate-grade non-Hodgkin's lymphomas (NHL) (n = 28) and high-grade NHL (n = 23) were significantly higher than those of the reactive hyperplasia (n = 25). The total for SPF + G2M of 6% was a satisfactory threshold for differentiating these NHL from reactive hyperplasia (sensitivity of 84%, specificity of 88%, and accuracy of 86%). However, low-grade NHL (n = 3) and Hodgkin's lymphoma (HL, n = 5) could not be discriminated by employing this parameter. DNA aneuploidy was seen in 13 of the 28 intermediate-grade NHL and 8 of the 23 high-grade NHL, whereas it was not seen in 25 reactive hyperplasia, 3 low-grade NHL, and 5 HL. The percentage of CD19-positive cells in B-cell NHL or CD3-positive cells in T-cell NHL was significantly higher compared with those for reactive hyperplasia. The percentage of CD16 + CD56-positive cells in natural killer (NK) cell NHL was extremely high, with a mean of 91.8%. Flow cytometric results for FNA-derived materials showed excellent correlation with those for surgical biopsy-derived specimens. Analyses of DNA ploidy, proliferative activities, and immunophenotype by flow cytometry (FCM) are useful for diagnosing intermediate- and high-grade NHL. Fine-needle aspiration is a less invasive approach than surgical biopsy, and, when combined with FCM, it may have a place in the diagnosis of NHL.

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the oral cavity and tongue base.

Nuclear deoxyribonucleic acid (DNA) content is a prognostic factor in several tumors, and decisions regarding treatment have been made using this parameter. Nevertheless, there is no agreement in head and neck cancer. The purpose of the present study was to ascertain whether tumor DNA content correlated with prognosis in cases of primary squamous cell carcinoma (SCC) of the oral cavity and tongue base. A retrospective study of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed SCC of the oral cavity and tongue base was performed using flow cytometry. Tumor DNA content was studied in 109 sets of specimens from previously untreated patients. All of them underwent surgical resection at the University "Hospital de La Princesa" between 1982 and 1992. Clinical parameters (age, sex, site of primary tumor, clinical stage, adjuvant therapy received, and disease-free and overall survival) and histologic parameters (histopathologic stage, tumor differentiation, type of inflammatory infiltration, presence of perineural invasion) were recorded in all cases. An exhaustive statistical analysis was applied. Only the histograms of 93 patients were adequate for consideration. In flow cytometric analysis, DNA aneuploidy was observed in 51 tumors (55%). The proportion of aneuploid tumors was significantly higher in advanced-stage carcinomas (p < .05), tumors with perineural invasion (p < .05) and in men (p < .05). In the 24 patients with lymph node metastasis, the incidence of aneuploidy was 82% (19 of 24) (p < .05). The rate of metastasis and aneuploidy increased as the degree of differentiation decreased (p < .05 for both). Patients with aneuploid carcinomas in both early and advanced stages had shorter relapse-free and overall survival periods than did the patients with diploid tumors (p < .001 for both). A Cox regression analysis demonstrated that ploidy was the single most important prognostic factor in determining relapse and death (p < .001 for both). The results indicate that tumor DNA analysis by flow cytometry appears to be useful as a supplement to clinical and histologic evaluation in predicting the tendency of SCC of the oral cavity and tongue base to metastasize to regional lymph nodes and to predict the outcome of the disease.

Diagnostic Accuracy of Urinary Cytology, and Deoxyribonucleic Acid Flow Cytometry and Cytology on Bladder Washings During Followup for Bladder Tumors

Purpose We evaluated the diagnostic accuracy of cytology on urine and bladder washings, and deoxyribonucleic acid (DNA) flow cytometry on bladder washings compared to cystoscopy during followup for bladder tumors. Materials and Methods A cross-sectional analysis was performed on 166 patients with a history of bladder tumor for the initial visit when cytology and DNA flow cytometry results were available for urine and bladder washing samples. There were 114 bladder tumor events and 52 negative controls (normal cystoscopy). A prospective study was conducted among the 66 patients with no tumor detected by cystoscopy at the initial visit and for whom the 3 test results were available. The patients were followed from this visit until tumor recurrence or the end of the followup period. Cytological examination was considered positive only when interpreted as malignant. Suspicious examinations were considered negative for the purpose of our study. Results Sensitivity and specificity of urinary cytology were 59 and 85%, respectively. Sensitivity was increased to 66% using bladder washing cytology whereas specificity was moderately decreased to 83%. The sensitivity and specificity of DNA aneuploidy were 45 and 87%, respectively. Inclusion within the aneuploid category of hyperdiploid samples (defined as more than 7% of cells in the S + G2M phase) increased sensitivity to 77%, while specificity decreased to 42%. Kaplan-Meier analysis of tumor-free survival in patients initially free of bladder cancer at cystoscopy showed an inability of DNA flow cytometry to predict recurrence, whereas positive urine or bladder washing cytology predicted a shorter time to recurrence (log-rank test p <0.01). Conclusions These results show that DNA flow cytometry and cytology on bladder washing samples add little information to that obtained from voided urine cytology.

Value of Deoxyribonucleic Acid Ploidy and Nuclear Morphometry for Prediction of Disease Progression in Renal Cell Carcinoma

Purpose A retrospective study was performed on 108 patients with localized renal cell carcinoma (pT1 to 3a N0M0) to determine whether ploidy and nuclear morphometry are independent predictive factors in addition to stage and grade. Materials and Methods Deoxyribonucleic acid (DNA) content was analyzed by flow cytometry and nuclear morphometry characterized by 5 nuclear descriptors. A Cox proportional hazards regression model was used to identify significant prognostic factors for disease progression. Results A model combining tumor stage and grade, DNA ploidy and nuclear minor axis was chosen as optimal with risk of disease progression increased with increasing tumor stage and grade, DNA aneuploidy and increasing nuclear minor axis. Conclusions This improved ability to predict disease progression in localized renal cell carcinoma may have important clinical use.

Rapidly Growing Histologically Benign Meningiomas

We present three cases of histologically benign meningiomas with a rapid and known time course to the development of symptoms. Tumor doubling time calculated from sequential computed tomographic scans and computer-assisted image analysis of proliferating cell nuclear antigen reactivity suggested rapid growth. Feulgen staining indicated deoxyribonucleic acid aneuploidy. Tests for progesterone and estrogen receptor immunoreactivity were negative. These cases are noteworthy for their uncharacteristically rapid growth in the absence of histological evidence of atypia.

Chromophobe Cell Renal Carcinoma: Clinicopathological Features of 50 Cases

Purpose We review the clinicopathological features of chromophobe cell renal carcinoma. Materials and Methods Cases were identified by reviewing the histology of all renal neoplasms resected between 1977 and 1990. Clinical data were obtained by chart review. Results Of 50 cases a majority (53 percent) were discovered incidentally and most (86 percent) were stage I. Typical pathological findings included the presence of 2 cell types (pale and eosinophilic), reactivity for Hale's colloidal iron, ultrastructural cytoplasmic vesicles and deoxyribonucleic acid aneuploidy. At last followup 47 patients (94 percent) were tumor-free or dead of unrelated causes. Survival was similar in patients with clear cell carcinoma of similar grade and stage. Conclusions Chromophobe cell carcinoma is a morphologically distinctive neoplasm with a favorable prognosis. Distinction from renal oncocytoma is important.

Deoxyribonucleic acid ploidy and S-phase fraction are not significant prognostic factors for patients with cervical cancer

Our purpose was to determine the usefulness of deoxyribonucleic acid ploidy and S-phase fraction as prognostic factors in patients with cervical cancer. Paraffin-embedded tumor specimens were obtained from 123 patients with cervical cancer (mean age 51 years, range 21 to 87 years). The mean follow-up period was 6.4 years. Deoxyribonucleic acid ploidy and S-phase fraction were determined by flow cytometry. A total of 119 patients were evaluable for deoxyribonucleic acid ploidy and 92 were evaluable for S-phase fraction. The overall rate of deoxyribonucleic acid aneuploidy was 60%, and the median S-phase fraction was 12.5%. Neither factor was significantly related to stage of disease. In univariate survival analyses patients with deoxyribonucleic acid aneuploid tumors had slightly better early survival than did patients with deoxyribonucleic acid diploid tumors (median survivals 2.7 and 1.4 years, respectively, p = 0.08 [Wilcoxon]), but the overall survival was not significantly different, p = 0.37 (log-rank). In multivariate analyses deoxyribonucleic acid ploidy was not a significant predictor of survival. S-phase fraction was not statistically significant in either analysis. Deoxyribonucleic acid ploidy and S-phase fraction are not useful prognostic factors for patients with cervical cancer.

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.

Prognostic value of deoxyribonucleic acid aneuploidy in primary non-small- cell lung carcinomas and their metastases : Liewald F, Hatz R, Storck M, Orend K-H, Weiss M, Wulf G, Valet G, Sunder-Plassmann L. Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-Univ. Med. School, Marchioninistr. 15, D-8000 Munich 70. J Thorac Cardiovasc Surg 1992; 104:1476–1482

Prognostic value of deoxyribonucleic acid aneuploidy in primary non-small- cell lung carcinomas and their metastases : Liewald F, Hatz R, Storck M, Orend K-H, Weiss M, Wulf G, Valet G, Sunder-Plassmann L. Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-Univ. Med. School, Marchioninistr. 15, D-8000 Munich 70. J Thorac Cardiovasc Surg 1992; 104:1476–1482

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.

Flow cytometric DNA analysis of 20 bronchopulmonary neuroendocrine tumours

Deoxyribonucleic acid (DNA) content of bronchopulmonary neuroendocrine tumours was measured by flow cytometry in order to investigate correlations between ploidy, S-phase fraction (SPF) and two histological classifications (World Health Organization (WHO), Warren and Gould), and clinical staging. A paraffin-embedded technique was used on 20 surgical specimens. Cases comprised (according to the classification of Warren and Gould) 7 carcinoids, 3 well-differentiated neuroendocrine carcinomas (WDNC), 6 intermediate neuroendocrine carcinomas (INC), and 4 small cell neuroendocrine carcinomas (SCNC). DNA aneuploidy was demonstrated in 3 out of 7 of the carcinoids, 3 out of 9 of the WDNCs and INCs, and 2 out of 4 of the SCNCs. A variable SPF was found in each group, except for the SCNCs which showed a constantly high SPF. In our small series, no correlation was noted between high SPF or aneuploidy and metastases. In conclusion, we observed no diagnostic value of malignancy for DNA aneuploidy. The SCNC group appeared to be an homogeneous group according to the SPF compared to the small cell carcinoma (SCC) group of the WHO classification. This and the prognostic incidence of high SPF need to be further studied.

Prognostic value of deoxyribonucleic acid aneuploidy in primary non-small-cell lung carcinomas and their metastases

The ploidy status of the deoxyribonucleic acid of a malignant lung tumor provides additional information besides histologic grading and tumor staging according to lymph node infiltration and tumor metastasis. Ninety-nine surgical specimens from patients with non-small-cell lung carcinoma were investigated by flow cytometry. Deoxyribonucleic acid aneuploidy was found in 48% of the primary tumors. Patients with deoxyribonucleic acid-euploid tumors showed better survival (p < 0.01) than those with deoxyribonucleic acid-aneuploid carcinomas independent of tumor stage. Deoxyribonucleic acid ploidy status of the primary tumor was compared with that of N2 lymph node metastases in 29 cases. Seven samples showed a change from deoxyribonucleic acid aneuploidy in the primary tumor to deoxyribonucleic acid euploidy in the lymph node metastases. Survival was significantly better for patients with euploid primary tumors and lymph node metastases, followed by patients with deoxyribonucleic acid-aneuploid primary tumors and euploid lymph node metastases. Survival was poorest in patients with deoxyribonucleic acid-aneuploid primary tumors and lymph node metastases. It was observed that only the simultaneous determination of deoxyribonucleic acid ploidy of primary tumors and lymph node metastases permits accurate prognostic evaluation in case of lymph node infiltration.

Prognostic Significance of Mucosal Aneuploidy in Stage Ta/T1 Grade 3 Carcinoma of the Bladder

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma.Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox’s proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.

Cell Kinetics by Bromodeoxyuridine Labeling and Deoxyribonucleic Acid Ploidy in Prostatic Carcinoma Needle Biopsies

We studied 63 prostate carcinomas in needle biopsies after labeling in vitro by incubating the entire biopsy specimen with tritiated thymidine or bromodeoxyuridine before fixation. Biopsies from 176 patients were labeled, of which 98 were benign and 78 were carcinomas (15 carcinomas were excluded because of scant tissue). The procedure did not interfere with histological diagnosis. Median labeling index was 0.87% (range 0.1 to 29.3%). A labeling index exceeding 3% was unusual but it may indicate the potential for rapid clinical progression. Deoxyribonucleic acid (DNA) flow cytometry was performed on the last 44 carcinomas using cells shed by the prostatic needle biopsy tissue samples during transportation to the pathology laboratory. A sufficient number of cells were obtained for analysis in 37 cases, of which 6 were DNA aneuploid. Labeling index correlated with Gleason histological grade and score, and data from the 6 DNA aneuploid carcinomas suggest association between DNA aneuploidy and a high labeling index. Estimates of percentage of S-phase cells by flow cytometry did not correlate with variables other than DNA index, and appear to have been affected by a high noise-to-signal ratio (few proliferative cells relative to cellular debris) and inability to discriminate between benign and carcinomatous cells.

Aneuploidy in pancreatic insulinomas does not predict malignancy

Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow-up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. Of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas.

Correlation of in vitro bromodeoxyuridine labeling index and DNA aneuploidy with survival or recurrence in brain-tumor patients

There are no previous reports correlating the in vitro bromodeoxyuridine (BUdR) labeling index (LI) with the clinical outcome in patients with brain tumors. The reliability of the LI as a predictor of patient survival or recurrence was examined in this study of 66 human brain tumors (19 gliomas, 18 meningiomas, and 29 others). Anti-BUdR staining was performed on surgically extirpated tumor tissue that had been treated with BUdR as previously described. Correlation of the BUdR LI with patient survival or tumor recurrence rate was carried out by the method of Kaplan and Meier. Deoxyribonucleic acid (DNA) aneuploidy was estimated in 52 cases. The results of this study indicate that BUdR LI values correlated well with the clinical course of patients with brain tumor. In comparison with patients with higher LI's, there was both a significantly higher survival rate for tumors other than meningiomas and a higher recurrence-free rate for meningiomas in patients with LI's of less than 4% and 1%, respectively. Although there was a tendency for patients without tumor aneuploidy to show better survival data than the others, no statistical difference was observed. These results suggest that the in vitro BUdR labeling method is reliable for prediction of a patient's prognosis, whereas prognosis on the basis of DNA aneuploidy alone is uncertain.