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PubMed1990

Changes in hepatocyte ploidy in response to chromium, analyzed by computer-assisted microscopy.

BDF1 mice were given single injections of sodium dichromate (25 mg/kg) on an acute (6 hr to 7 days) or intermediate (2-4 weeks) basis, or multiple injections (12.5 mg/kg) on a chronic (4.5 months) basis. Observed hepatic changes included programmed cell death (apoptosis) in the periportal region with acute exposure and fusion of liver lobes with chronic exposure. Response to chromate exposure was measured by change in hepatocyte nuclear ploidy state (e.g., the proportion of diploid, tetraploid, and octaploid nuclei) based on computer-assisted imaging from histological sections. The computer-assisted imaging system used in this study was superior to traditional methods because it (1) allows rapid ploidy determinations from histological material and (2) can be used to collect regional information. Regional differences in ploidy were seen to occur in a consistent fashion among both control and treated animals. Nuclei adjacent to the portal triad had the lowest ploidy value (highest proportion of diploid nuclei), an intermediate value was found adjacent to the central vein, and the highest ploidy was found in the midzone. These three ploidy-based zones roughly correspond to the three functional zones of A. M. Rappaport (1973, Microvasc. Res. 6, 212-228) and W. H. Lamers et al. W. H. Lamers, A. Hilberts, E. Furt, J. Smith, G. N. Jonges, J. F. Van Noorden, J. W. G. Janzen, R. Charles, and A. F. M. Moorman, 1989, Hepatology, 10, 72-76. Temporal changes in ploidy were seen among control animals (all zones), with young animals (56 days) displaying relatively low ploidy values compared to older animals (184 days). Chromate exposure caused increased ploidy (all zones) among animals treated on an acute basis (the youngest animals). Chromate had no apparent effect on ploidy among animals treated for longer periods of time, probably because of age-related factors.

Aging↗
PubMed1999

Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.

Adult↗
PubMed1990

Diagnostic significance of fluorocytophotometric DNA ploidy analysis of gastric cancer with special reference to its comparison with clinical and histopathological diagnosis.

Mithramycin binds stoichiometrically with G-C pairs of nucleotides, thus it is useful for nuclear DNA fluorocytophotometry. In the present study, relationships between clinical features and nuclear DNA ploidy values were explored in 80 gastric cancer cases. For the first time, nuclear DNA ploidy values of tumor tissues even in the same gastric cancer were found to be not always identical, when those were determined at two different sites in the same layer or at two different depths of cancer invasion. The highest DNA ploidy values greater than 9C of the original tumors were significantly more frequently observed in advanced cancer than in early cancer. The highest DNA ploidy values greater than 12 degrees C of the original tumors were significantly more frequently observed in gastric cancer cases with lymph node metastases than in those without lymph node metastases. The highest DNA ploidy values of metastatic tumors in lymph nodes were significantly greater than those of the original tumors. The cell lines with very high nuclear DNA ploidy values, however, usually do not establish new stem lines in metastatic lymph nodes. Borrmann 2 gastric cancer which was clinically diagnosed as the localized type often showed much greater nuclear DNA ploidy values and higher incidence of metastases than Borrmann 3. Therefore, it is not true that Borrmann 2 gastric cancer is less malignant than Borrmann 3. When cancer cells invaded onto the peritoneal surface, through the serosal layer, the highest nuclear DNA ploidy values are significantly reduced for unknown reasons. Therefore, it should be kept in mind that the reduction of highest nuclear DNA ploidy values in these invasive types of gastric cancer patients does not necessarily mean a good clinical sign. Nuclear DNA ploidy analysis is the effective means of cell biological diagnosis for gastric cancer.

Adult↗
PubMed1990

The relationship between megakaryocyte ploidy and platelet volume in normal and thrombocytopenic C3H mice.

Previous studies have suggested that platelet volume may be primarily regulated by the ploidy distribution of mature bone marrow megakaryocytes. However, earlier investigations from this laboratory using C57/BL mice have shown that in response to acute, severe, or moderate thrombocytopenia, platelet volume is regulated independently of megakaryocyte ploidy. Murine strains, including C57/BL, usually have a modal bone marrow megakaryocyte ploidy class of 16N. In contrast, the C3H mouse has a 32N modal bone marrow megakaryocyte ploidy class. We have examined the platelet count, platelet volume distribution, and bone marrow megakaryocyte ploidy distribution of C3H mice during steady-state thrombopoiesis and after depletion of platelets by antiplatelet serum. The platelet count and volume of normal C3H mice were not substantially different from those of C57/BL mice, but megakaryocyte frequency was marginally greater (p less than 0.05), and the ploidy distribution exhibited a a marked reduction in the proportion of 16N cells (p less than 0.001) and increased relative frequencies of 32N (p less than 0.001) and 64N (p less than 0.01) megakaryocytes. In response to acute severe thrombocytopenia, C3H mice demonstrated an increase in platelet volume equivalent to that previously reported for C57/BL mice, without a subsequent shift in the modal megakaryocyte ploidy class. The relative frequencies of 64N and 128N megakaryocytes increased significantly (p less than 0.005) compared to normal C3H mice, without a change in the frequency of 32N megakaryocytes. These studies indicate that during steady-state thrombopoiesis, a greater proportion of higher ploidy megakaryocytes (32N plus 64N) does not necessarily alter peripheral platelet count or platelet volume. Therefore, it appears that neither platelet volume nor count are primarily regulated by bone marrow megakaryocyte ploidy and that the magnitude of upward regulation of megakaryocyte ploidy is limited.

Animals↗
PubMed1988

DNA ploidy is closely linked to tumor invasion, lymph node metastasis, and prognosis in clinical gastric cancer.

DNA ploidy microspectrophotometrically determined in 254 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. DNA distribution patterns were grouped into low and high ploidies. The 24.0% frequency in the high ploidy group, at the mucosal stage, increased in proportion to invasion into the deeper layers. There was a high incidence of lymph node metastasis in the high ploidy group, compared with the low ploidy group, in case of invasion beyond the mucosa. Widespread nodal involvement was frequent in the high ploidy group. The 5-year survival rate was 73.7% in patients of high ploidy, with a statistical difference compared to the 90.6% in those of low ploidy (P less than 0.01). In the multivariate analysis of 226 patients undergoing curative surgery, the DNA ploidy proved to be a major independent prognostic factor. These findings indicate a close correlation among DNA ploidy, tumor invasion and nodal involvement, and the significant clinical value of DNA analysis for predicting the prognosis in patients with gastric carcinoma.

Aged↗
PubMed1981

Ploidy effects on anatomy and gas exchange of tall fescue leaves.

A growth chamber study was designed to interpret differences in CO(2) exchange rate (CER) and leaf diffusive resistance among 4X, 6X, 8X, and 10X ploidy levels of tall fescue (Festuca arundinacea, Schreb). Mesophyll cell size, stomatal density, number of major and minor veins, and bundle cap size of leaf blades were evaluated. Diffusive resistance tended to decrease and CER to increase with increasing ploidy level. Mean stomatal density decreased from 43.6 per square millimeter to 30.6 per square millimeter as ploidy level increased from 4X to 8X. The 10X ploidy level exhibited the highest stomatal density, 47.2 per square millimeter. Major veins decreased from a mean of 14.2 to 10.2, and minor veins increased from a mean of 4.2 to 6.6, per leaf blade as ploidy increased from 4X to 10X. Total number of veins decreased significantly from a mean of 18.4 to 15.7 as ploidy increased from 4X to 8X.Length and width of mesophyll cells tended to increase as ploidy increased from 4X to 8X, but then decreased again at 10X. The number of cells in the bundle cap showed no trend among ploidy levels. Estimated volume of mesophyll cells increased six times between the 4X and the 6X level while chromosome number of nuclear DNA per cell increased only 50%. However, increases in estimated cell volume were proportional to chromosome number as ploidy increased from 6X to 8X. The relationship between cell volume and chromosome number at 10X was intermediate between that at 4X and 6X or 8X.Differences in stomatal density and diffusive resistance did not fully account for the ploidy effect on CER. Further mesophyll cell volume was positively related to CER, a factor contrary to earlier experiments.

Journal Article↗
PubMed1991

The prognostic significance of ploidy analysis in operable breast cancer.

The nuclear DNA content of 98 operable breast cancers was determined by flow cytometric analysis using paraffin-embedded tissue. All patients were on follow-up and failure of treatment or recurrences were identified. DNA ploidy data in the form of ploidy status and DNA index (DI) has been correlated with various clinical and histopathologic factors. The only significant correlation using univariate analysis exists between the histologic grade and DI (P less than 0.025), recurrence of the disease and ploidy status (P less than 0.005), and recurrence of the disease and DI (P less than 0.005). The absence of correlation of ploidy status with other tumor derived factors indicates the independent nature of ploidy as a prognostic factor. Multivariate analysis showed that in the whole-group ploidy (P less than 0.01), tumor margin (P less than 0.01), and menopausal status (P less than 0.01) were significant factors in the order mentioned. DI with a cut of at 1.29 is not found to be a significant factor in the multivariate analysis. The maximum prognostic value of ploidy status was observed in the postmenopausal group (P less than 0.0005). In the node-negative group ploidy status (P less than 0.05) is the only independent significant factor predicting for early relapse. It is concluded that ploidy status is an independent prognostic factor predicting for recurrence of the disease. In the node-negative subgroup this could be used to identify the subset of patients who may benefit from adjuvant treatment.

Breast Neoplasms↗
PubMed1984

The relation of megakaryocyte ploidy to platelet volume.

To determine how alterations of megakaryocyte proliferation will affect platelet production, we measured mean platelet volume (MPV), platelet volume heterogeneity, platelet count, and mean megakaryocyte ploidy in 42 patients. In normal subjects, mean platelet volume and megakaryocyte ploidy were related inversely but nonlinearly to platelet count, whereas mean platelet volume and platelet volume heterogeneity were related directly. In patients with immune thrombocytopenic purpura (low platelet count, MPV above normal, and increased megakaryocyte ploidy), and in those with reactive thrombocytosis (high platelet count, low MPV and megakaryocyte ploidy), the relation of MPV to megakaryocyte ploidy, platelet volume heterogeneity, and platelet count resembled or extended the relations found in normal subjects. By contrast, in patients with aplastic anemia or megaloblastic anemia, or in patients who were undergoing chemotherapy for leukemia, heterogeneity was increased abnormally at any MPV, and both MPV and megakaryocyte ploidy were substantially lower, at any platelet volume, than in normals or the above other groups. The most common ploidy class was 8N in all patients, and the mean megakaryocyte ploidy correlated directly and linearly with mean platelet volume. The data show that bone marrow with megakaryocytes of higher ploidy produces platelets that are both larger and more heterogeneous.

Blood Platelets↗
PubMed1988

Analysis of murine megakaryocyte colony size and ploidy: effects of interleukin-3.

Megakaryocytes develop from diploid precursor cells that, after variable numbers of mitoses, cease cell division and then undergo synchronous nuclear endoreduplication (endomitosis). Megakaryocyte colony formation represents an in-vitro model of these processes in which the number and ploidy of colony cells reflect the activity of the mitotic and endomitotic pathways, respectively. We have analyzed the size and ploidization of murine megakaryocyte colonies grown in agar and examined the influence of interleukin-3 (IL-3) on these parameters. Colonies were identified in situ by staining for acetylcholinesterase and the ploidy of colony cells was determined by fluorescence cytophotometry. More than 98% of the megakaryocytes that developed in culture could be analyzed. In cultures of unfractionated marrow cells stimulated by either pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM, a crude source of megakaryocyte colony-stimulating activity) or IL-3, the modal ploidy of day-5 colony megakaryocytes was 16N (range 2N-128N). The distribution of colony size was described by an inverse exponential relationship. Colony size and geometric mean ploidy were inversely correlated under conditions of maximal stimulation with PWM-SCM and at all concentrations of IL-3 tested. Increasing concentrations of IL-3 in cultures of either unfractionated marrow cells or nonadherent T-lymphocyte-depleted (NATD) marrow cells stimulated similar dose-dependent increases in the mean size and numbers of megakaryocyte colonies but did not significantly alter their ploidy distribution. However, the mean ploidy of colony megakaryocytes in IL-3-stimulated cultures of NATD marrow cells was significantly less (P less than 0.001) than the mean ploidy of megakaryocytes in IL-3-stimulated cultures of unfractionated marrow cells. The mean ploidy of megakaryocytes, which developed in PWM-SCM-stimulated cultures, was not affected by initial accessory cell depletion. We conclude that the size and ploidy characteristics of day-5 murine megakaryocyte colonies are structured as continua and that IL-3 stimulates an increase in mean colony size and numbers without affecting ploidization. T-lymphocytes and adherent cells elaborate an activity which promotes endomitosis in vitro; factors in PWM-SCM can substitute for this activity.

Animals↗
PubMed2000

Relationship of DNA ploidy to hormone receptor status and proliferation in invasive breast carcinoma.

PURPOSE: In 247 primary invasive breast carcinomas, DNA ploidy was related to hormone receptor status, proliferation, and clinical/histopathologic factors. METHODS: DNA ploidy analysis was performed by image analysis using imprints. Estrogen (ER) and progesterone (PR) receptor status was determined immunohistochemically. The proliferative activity of the tumours was assessed by Ki-67 antigen labelling. Total observation time was 3.5 years. RESULTS: DNA ploidy analysis revealed a high fraction of tumours with non-peridiploid patterns (78%). Significant correlations between DNA ploidy and ER/PR receptor status (P < 0.01) were found with increased frequencies of peridiploid DNA results in receptor positive tumours. A significant relationship became manifest between DNA ploidy and Ki-67 index showing high frequencies of non-peridiploid DNA patterns in tumours with Ki-67 index > 20% (P < 0.01). There was a strong correlation (P < 0.001) between DNA ploidy and histopathologic grading, while tumour size and lymph node status were not correlated to DNA ploidy. CONCLUSIONS: The results of our study on invasive breast carcinoma demonstrate that DNA ploidy measured by image analysis is predominantly associated with markers of cell differentiation. Preliminary outcome data reveal a risk-indicating potential of DNA ploidy primarily in cases with favourable results for other prognostic factors.

Breast Neoplasms↗
PubMed1995

Progression of canine mammary tumours as reflected by DNA ploidy in primary tumours and their metastases.

Thirty dogs with metastasizing mammary tumours (carcinomas, n = 22; sarcomas, n = 8) were necropsied. Flow cytometric DNA analysis was carried out on frozen primary tumours and on selected metastases from the dogs. Ductular carcinomas (n = 13) had a varying growth pattern, in terms of histology, in both the primary tumours and metastases and between different metastases. The different types of DNA ploidy, including hypodiploidy, in the primary ductular carcinomas were also seen in the tumour metastases. Dogs with primary anaplastic carcinomas (n = 7) had multiple metastases, which were in most cases near-diploid or hyperdiploid. Two dogs had spindle-cell carcinomas, which were hypodiploid in both the primary tumour and the metastases. The DNA ploidy in the metastases was retained in 16 of the 22 dogs with primary carcinomas. Fibrosarcomas (n = 5) showed different types of DNA ploidy. In two of the three dogs with diploid or near-diploid osteosarcomas, the DNA ploidy was retained in the metastases. There was a statistically significant association between mammary tumours and metastases (P = 0.0001) in terms of both histological diagnosis and DNA ploidy. The association was retained when the carcinomas were tested separately (P = 0.0001); in the sarcomas it was retained weakly in terms of histology (P = 0.0183) but not DNA ploidy (P = 0.6659). The retention of the DNA ploidy in most carcinoma metastases indicated that selection of DNA ploidy had taken place prior to metastasis. The differences in patterns of DNA ploidy between ductular and anaplastic carcinomas may reflect different pathogenesis in these types of canine mammary tumour.

Animals↗
PubMed2001

Relationship of hepatocyte ploidy levels with body size and growth rate in mammals.

To elucidate possible causes of the elevation of genome number in somatic cells, hepatocyte ploidy levels were measured cytofluorimetrically and related to the organismal parameters (body size, postnatal growth rate, and postnatal development type) in 53 mammalian species. Metabolic scope (ratio of maximal metabolic rate to basal metabolic rate) was also included in 23 species. Body masses ranged 10(5) times, and growth rate more than 30 times. Postnatal growth rate was found to have the strongest effect on the hepatocyte ploidy. At a fixed body mass the growth rate closely correlates (partial correlation analysis) with the cell ploidy level (r = 0.85, P < 10(-6)), whereas at a fixed growth rate body mass correlates poorly with ploidy level (r = -0.38, P < 0.01). The mature young (precocial mammals) of the species have, on average, a higher cell ploidy level than the immature-born (altricial) animals. However, the relationship between precocity of young and cell ploidy levels disappears when the influences of growth rate and body mass are removed. Interspecies variability of the hepatocyte ploidy levels may be explained by different levels of competition between the processes of proliferation and differentiation in cells. In turn, the animal differences in the levels of this competition are due to differences in growth rate. A high negative correlation between the hepatocyte ploidy level and the metabolic scope indicates a low safety margin of organs with a high number of polyploid cells. This fact allows us to challenge a common opinion that increasing ploidy enhances the functional capability of cells or is necessary for cell differentiation. Somatic polyploidy can be considered a "cheap" solution of growth problems that appear when an organ is working at the limit of its capabilities.

Animals↗
PubMed2004

DNA-ploidy in advanced gastric carcinoma is less heterogeneous than in early gastric cancer.

This analysis of DNA-ploidy heterogeneity in advanced gastric carcinomas is consistent with the hypothesis of the emergence of a single aneuploid cell clone as a crucial mechanism in the progression from early gastric carcinoma to advanced gastric cancer. The prognostic value of DNA-ploidy in gastric cancers has been a matter of controversy. Tumour DNA-ploidy heterogeneity, the presence within the same tumour of multiple stemlines differing in DNA content, has been described in various tumours including gastric cancers. The occurrence of such heterogeneity has been accepted as an explanation for the divergent DNA-ploidy results in this type of tumours. A previous study of early gastric cancers suggested that in pure diploid superficial carcinomas, genetic instability might lead to a cell clone which has undergone a ploidy shift and is more aggressive. If so, this would initially result in DNA-ploidy heterogeneity. Proliferative dominance of the aneuploid clone could eventually evolve to a homogeneous aneuploid tumour. In order to test this hypothesis, we studied DNA-aneuploidy and DNA-ploidy heterogeneity in advanced gastric carcinomas. We performed DNA cytophotometry on multiple samples collected from 16 advanced gastric carcinomas and found 15 DNA-aneuploid tumours (94%) and one diploid tumour. Multiple DNA-stemlines were found in 4 cases (26%). Analysis of proliferative activity performed on the same samples revealed higher proliferation rate in DNA-ploidy homogeneous tumours than in aneuploid heterogeneous tumours. Heterogeneous tumours did not overexpress p53. These results confirm that DNA-aneuploidy is frequent in advanced gastric cancer and demonstrate that a majority of these aneuploid tumours are not DNA-ploidy heterogeneous. Furthermore, the higher proliferative activity in homogeneous-aneuploid carcinomas and their more frequent overexpression of p53 support the hypothesis that in gastric cancer tumour progression implies the development of a dominant and more aggressive (higher proliferative activity, p53 overexpression) aneuploid cell clone.

Aged↗
PubMed1992

Comparison of cytofluorometric nuclear DNA ploidy analysis on fresh and paraffin embedded specimen.

The cytofluorometric nuclear DNA ploidy analysis was performed in gallbladder (GB) epithelium of eight patients of chronic cholecystitis to make a comparison between fresh and paraffin embedded tissue analysis, to make an ideal single cellular suspension, to evaluate the ploidy pattern affected by inflammation and to assess the histological correlations. Six (75%) fresh specimens and eight (100%) paraffin embedded specimens showed diploidy pattern of histogram. Two (25%) fresh specimens showed low ploidy pattern of histogram. There was a good correlation between histological findings and the ploidy patterns of 100% paraffin embedded specimens and 75% fresh specimens. The relative fluorescence intensity was found higher and more stable in paraffin embedded tissues than fresh tissues. Inflammation did not affect the ploidy patterns of paraffin embedded specimens whereas the ploidy patterns of fresh specimens were affected. It can be concluded that the DNA ploidy patterns and histological findings have a good correlation and inflammation does not affect the cytofluorometric DNA ploidy pattern when using the paraffin embedded specimens. Paraffin embedded specimens are superior to fresh specimens for making an ideal single cellular suspension to obtain stable, high, and accurate fluorescence intensity with less background fluorescence which makes the ploidy pattern behave like exact behavior of tissues.

Cholecystitis↗
PubMedDate not supplied

Prognostic value of DNA ploidy patterns of colorectal adenocarcinoma.

BACKGROUND/AIMS: The significance of prognostic value of DNA ploidy patterns of colorectal cancer has not yet been fully understood. The present study was designed to determine the prognostic value of DNA ploidy patterns for colorectal adenocarcinomas after resection. METHODOLOGY: We have prospectively collected tumor specimens from 420 patients with colorectal cancer since 1996. The DNA ploidy patterns were determined with the use of DNA flow cytometry. The correlation of DNA ploidy pattern and various characteristics of tumors and the prognostic significance of DNA ploidy patterns were evaluated by univariate as well as Cox's proportional hazard model. The disease-free survival curves were calculated with Kaplan-Meier's analysis, and the survival difference was determined by log-rank test. RESULTS: DNA ploidy patterns were diploid in 115 (27.4%) and aneuploid in 305 patients (72.6%). The pattern of DNA ploidy did not correlate with age, gender, location, differentiation, and stage of the tumors. In 146 patients who were followed up for at least 2 years, the disease-free survival curves were similar between the diploid and aneuploid group. Multivariate analysis disclosed that tumor staging was associated with the survival of patients but the DNA ploidy pattern had no prognostic significance. CONCLUSIONS: The DNA ploidy pattern was not a significant prognostic factor in short-term follow-up.

Adenocarcinoma↗
PubMed2005

The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer.

OBJECTIVE: In a previous study, we mapped the ploidy heterogeneity of prostate cancer using flow cytometry in 676 tumor samples from 50 radical prostatectomy specimens. Ploidy heterogeneity was common (42% of tumors) and was found in all non-diploid tumors. The volume of non-diploid tumor was estimated and found to predict extra-prostatic extension and seminal vesicle invasion. The aim of this study was to evaluate the impact of tumor heterogeneity on preoperative ploidy assessment. MATERIAL AND METHODS: In 50 men at least six core biopsies were taken before prostatectomy. Sections from biopsies with cancer were Feulgen-stained for image cytometry. After exclusion of biopsies with insufficient material, 123 histograms from 48 men (mean 2.6; range 1-7) remained for analysis. RESULTS: In 32 men, biopsies were diploid. In 16 men, at least one biopsy was non-diploid (14 tetraploid, two aneuploid) and 10 of them also had diploid biopsies. In 34 men (71%), the prostatectomy specimens were correctly predicted as being either diploid (48%) or non-diploid (23%). The sensitivity and specificity of biopsies for predicting non-diploid cancer were 55% and 82%, respectively, and the positive and negative predictive values were 69% and 72%, respectively. The ploidy status of tumors with and without ploidy heterogeneity was correctly predicted in 55% and 82% of cases, respectively (p=0.04). Biopsies underestimated ploidy in 9/20 tumors (45%) with heterogeneous ploidy status. Underestimation mainly occurred when one or two cores were analyzed. CONCLUSIONS: Preoperative prediction of the ploidy status of prostate cancer is hampered by tumor heterogeneity. Analysis of multiple biopsies is important for correct preoperative ploidy estimation.

Aged↗
PubMed1990

Prognostic value of S-phase fraction and DNA ploidy studied with in vivo administration of bromodeoxyuridine on human gastric cancers.

The authors studied the prognostic values of DNA ploidy pattern and proliferative activity with in vivo administration of bromodeoxyuridine in human gastric cancers. Fresh specimens surgically removed from 117 patients with gastric cancer were investigated by flow cytometric study using a monoclonal antibody to bromodeoxyuridine. DNA ploidy patterns were classified into four types according to the bivariate BrdUrd/DNA distribution: D1, tumors with single diploid population; D2, tumors which showed mosaic of diploid and aneuploid population; A1, tumors with single aneuploid population; and A2, several aneuploid populations without diploid population. The numbers of cases of each ploidy pattern were as follows: D1, 36 cases (30.8%); D2, 38 cases (32.5%); A1, 15 cases (12.8%); and A2, 27 cases (23.1%). DNA ploidy pattern and S-phase fraction (SPF) showed no relation with clinicopathologic findings, except for type A2. In type A2, lymph node metastasis and lymphatic vessel invasion were observed more often than type D1. The SPF calculated from the bivariate BrdUrd/DNA distribution was higher in aneuploidy (D2, A1, and A2) than in diploidy (D1) (P less than 0.01). Also, A2 exhibited a higher SPF than A1 (P less than 0.01). Furthermore, SPF correlated with DNA index significantly (P less than 0.01). Patients who showed aneuploid tumors, DNA ploidy type A2, or SPF of more than 10% survived 3 years less than those with diploid tumors, DNA ploidy type D1, or SPF of less than 10%, respectively (P less than 0.05). By analyzing with the Cox's proportional hazard's model, it is revealed that DNA ploidy and SPF are one of the independent factors of prognostic significance. The results indicated that the patients with aneuploid tumors or highly proliferative tumors had a poor prognosis and that DNA ploidy pattern and SPF were useful prognostic factors for gastric cancers.

Bromodeoxyuridine↗
PubMed2001

Prognostic value of DNA ploidy in 653 Japanese women with node-negative breast cancer.

BACKGROUND: The prognostic value of DNA ploidy has been extensively studied in breast cancer; however, the results remain controversial. Flow cytometry (FCM) studies of DNA ploidy on frozen sections have not yet been performed in a large series of Japanese women with node-negative breast cancer. METHODS: An FCM analysis of DNA ploidy was performed on frozen sections of node-negative breast cancer from 653 Japanese women, with a mean follow-up duration of 46 months. RESULTS: Three hundred and twenty-four (49.6%) patients showed a diploid tumor, while 329 (50.4%) showed an aneuploid tumor. There was a significant correlation between DNA ploidy and estrogen receptor (ER) status. Patients with an aneuploid tumor had a significantly worse outcome in terms of both disease-free survival (DFS; P = 0.0116) and overall survival (OS: P = 0.0492) than those with a diploid tumor, while the same effect, in terms of DFS, was also seen in ER-positive breast cancer. Multivariate analyses indicated DNA ploidy to be an independent prognostic factor for DFS, while DNA ploidy and tumor size were found to be independent prognostic factors for OS. DNA ploidy was also shown to be an independent prognostic factor for DFS in ER-positive breast cancer. CONCLUSION: Our findings demonstrated DNA ploidy, based on FCM, to have an important prognostic value in Japanese women with node-negative breast cancer.

Adult↗