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PubMed2000

Clonal heterogeneity in sporadic melanomas as revealed by loss-of-heterozygosity analysis.

The major obstacle preventing effective treatment of melanoma is the biological heterogeneity of tumor cells. This study was performed to determine clonal genetic heterogeneity within primary melanoma and the evolution of these heterogeneous sub-clones during disease progression. DNA samples were obtained from 44 morphologically distinct areas identified within 10 primary tumors and from 15 metastases in the same patients. Loss of heterozygosity (LOH) analyses were performed using 17 microsatellite markers that mapped to chromosomes 6q, 9p, 10q and 18q, the most frequently deleted in melanoma. Of 10 primary tumors, 8 were revealed to have intratumoral genetic heterogeneity in terms of LOH of the 4 chromosome arms examined, 7 containing at least 2 different sub-clones harboring LOH of different chromosome areas, while the remaining one tumor showed prominent intratumoral genetic heterogeneity consisting of at least 6 genetically distinct sub-clones. LOH of 6q was detected only in a sub-set of multiple microdissected samples in most of the primary tumors, but was most frequently detected in metastases, suggesting that loss of this chromosome arm occurred late and played an important part in metastatic progression. Comparison of LOH between sub-clones within primary tumors and within metastases showed the divergence of metastatic clones from dominant populations within the primary tumor in 5 patients, whereas in the remaining three patients parent sub-clones were not identified, or constituted only a minor sub-population within the primary tumors. These results, showing considerable genetic heterogeneity in sporadic melanoma, have profound implications for the choice of future therapeutic strategies.

Adult↗
PubMed2002

[Review on landscape heterogeneity].

On the base of precedent studies, the occurring mechanism, classification, measurement methods, and the important role of landscape heterogeneity in landscape ecology were reviewed. The inner and outer uncertain factors result in landscape heterogeneity. Landscape heterogeneity has close relations with landscape stability, landscape design, architecture, management and disturbance, scale and ecological diversity in ecology. Complexity of landscape heterogeneity research, non-system of measurement indices and methods, difficulties and limitations of landscape heterogeneity modelling were all discussed respectively. In addition, it is suggested that the theory and methods of ecological complexity should be used to improve landscape heterogeneity research.

Data Interpretation, Statistical↗
PubMed2003

Using flow cytometry to quantify microbial heterogeneity.

Flow cytometry is a powerful technique for the study of single cells, and thus it is of particular utility in the study of heterogeneity in microbial populations. This review seeks to highlight the role of flow cytometric analyses in studies of microbial heterogeneity, drawing wherever possible on recently published research articles. Whilst microbial heterogeneity is well documented in both natural and laboratory environments, the underlying causes are less well understood. Possible sources for the heterogeneity that is observed in microbial systems are discussed, together with the flow cytometric tools that aid its study. The role of flow cytometry in molecular biology is discussed with reference to gene reporter systems, which enable heterogeneity of gene expression to be monitored. With the recent sequencing of a variety of microbial genomes, it is anticipated that flow cytometry will have an increasing role to play in studying the effects of gene expression and mutation on heterogeneity, and in resolving the interactions of genetics and physiology.

Bacteria↗
PubMed2003

Heterogeneity of cerebral blood flow in Alzheimer disease and vascular dementia.

BACKGROUND AND PURPOSE: Alzheimer disease (AD) and vascular dementia (VaD) are the two major diseases that cause dementia, and early diagnosis is important. Single photon emission CT (SPECT) of cerebral blood flow (CBF) is used for the early detection of dementia and as an auxiliary method for follow-up. AD shows reduced posterior blood flow and VaD manifests reduced anterior blood flow on CBF SPECT images. We examined the usefulness of 3D fractal analysis of CBF SPECT images to objectively quantify the heterogeneity of CBF in patients with AD and VaD. METHODS: Thirty-two patients with AD and 22 with VaD based on neuropsychologic tests and imaging findings, as well as 20 age-matched control subjects underwent technetium-99m hexamethyl propyleneamine oxime CBF SPECT. We then conducted statistical image processing by 3D fractal analysis on reconstructed data. Fractal dimension, an index of heterogeneity, was then calculated for the whole brain, as well as for the anterior and posterior regions of the brain. A higher fractal dimension indicates that the CBF SPECT image is uneven. The ratio of fractal dimension of the anterior region to fractal dimension of the posterior region (A/P ratio) was calculated. Heterogeneity of CBF was compared among the AD, VaD, and control groups. RESULTS: Fractal dimensions of the AD, VaD, and control groups were 1.072+/-0.179 (mean +/- SD), 1.005+/-0.156, and 0.806+/-0.06, respectively. A significant difference of fractal dimension was noted between the control group and the two types of dementia (P<.0001); however, no significant difference was noted between the AD and VaD groups. The A/P ratios of the AD and VaD groups were significantly different (0.952 and 1.163, respectively; P<.01). CONCLUSION: Analysis of CBF SPECT images quantitatively showed that the fractal dimension was significantly higher (indicating heterogeneity) in patients with AD and VaD when compared with age-matched control subjects. Comparison of the A/P ratio on CBF SPECT images between AD and VaD groups showed that the heterogeneity of CBF was posterior-dominant for AD and anterior-dominant for VaD. Thus, 3D fractal analysis enabled a simple and objective evaluation of the heterogeneity of CBF in patients with AD and VaD.

Aged↗
PubMed2003

[Spatial heterogeneity of vegetation and soil characteristics in oasis-desert ecotone].

The spatial distribution of bio- and abiotic factors in ecosystem has the features of spatial heterogeneity in general, and spatial heterogeneity is important in the function and process of ecosystem at a variety of scales. In this paper, semivariance theory and methods were used to study the degree, composition, scale and pattern of spatial heterogeneity of vegetation coverage and soil environment factors, and their relationships in the Fukang oasis-desert ecotone of Xinjiang. With block kriging in the studied area of sampling, the spatial pattern of each factor was expressed in three dimensions as well. The results indicated that except the little spatial autocorrelation of salt salinity, there existed a spatial autocorrelation above mean of the other factors, and the spatial variation was mainly limited to smaller scales. The vegetation coverage, for which auto-correlated spatial heterogeneity was a main component, had a high degree of spatial heterogeneity with obvious spatial pattern at the scale of 3 km. From the perspective of spatial distributions, there existed a remarkable difference between soil holard and soil pH value in the studied area. Besides this, the higher value areas interleaved with the lower ones, significant positive correlations were observed between herbage coverage and soil factors (surface SH and SPH), and shrub coverage depended on the deep SH. The difference of spatial heterogeneity and pattern between SC and HC indicated the different ecological function and process in the ecosystem.

Desert Climate↗
PubMed1992

Cellular heterogeneity and mutant oestrogen receptors in hormone resistant breast cancer.

In summary, we propose that the molecular heterogeneity of ER in breast tumour cells, characterized by the presence of mutant receptor forms, generates the cellular heterogeneity evident when PR or DNA ploidy are analysed in cell subpopulations. Furthermore, it is likely that cellular heterogeneity leads to the lack of uniformity in response to tamoxifen that we have described. We find that heterogeneity of PR and DNA ploidy reflects the existence of mixed subpopulations of breast cancer cells that are substantially remodelled under the influence of tamoxifen. It appears likely that different subsets of cells, rather than being "resistant", can be inhibited or stimulated by tamoxifen and that their suppression or outgrowth alters the phenotype of the tumour. PR heterogeneity in solid tumours of patients may predict a mixed, and potentially dangerous, response to anti-oestrogen treatment. As we learn more about the heterogeneity of PR, ER and other proteins in tumours, we may be able to recognize such lethal subpopulations, which the flow cytometry immunoassay can simply and rapidly measure. Our data also suggest that the use of tamoxifen as a chemopreventant in women at high risk of developing breast cancer (Kiang, 1991) should be viewed with caution.

Breast Neoplasms↗
PubMed1992

[Integration of informations gained from heterogeneic world of myocardial function and ischemia].

Currently, heterogeneity is the word to describe any inhomogeneous phenomenon observed in the ever changing living creatures. Myocardial function is dynamic in nature which is a summation of many inhomogeneous components. In fact, heterogenic phenomenon has been observed both at cellular and at ventricular levels during myocardial contraction and relaxation. However, this heterogenic behavior of myocardial activities serves as a source of monitoring parameters by which we can grasp what is happening in the patient. Reliance on only one of those parameters would lead to a wrong diagnosis and judgement in the heterogenic world. We, therefore, need to integrate those parameters to form more realistic image about patient's status. We have to have a cut off point to divide what is right and what is wrong. Although the truth may not be reached eventually from heterogeneous informations, an appropriate method to integrate informations in the heterogenic world will aid us to come closer to the reality.

Humans↗
PubMed2004

Regional heterogeneity of EGFR gene amplification and nuclear morphology in glioblastomas. An investigation using laser microdissection and pressure catapulting.

OBJECTIVE: To study the regional heterogeneity of epidermal growth factor receptor (EGFR) gene amplification (EGFR-GA) in glioblastomas, considering the relationship between this mutation and morphology of tumor cell nuclei. STUDY DESIGN: Tissue samples gained by laser microdissection and pressure catapulting were used for the performance of differential polymerase chain reaction in 32 morphologically different regions from 7 glioblastomas. Semiquantitative determination of EGFR expression and image analysis of tumor cell nuclei were performed in the same regions. RESULTS: Distinct regional differences concerning the degree of EGFR-GA were found in 2 tumor cases. When comparing regions with different degrees of gene amplification within these cases, morphologic differences in tumor cell nuclei were observed. The other tumor cases also showed distinct intratumoral heterogeneity concerning histomorphology but no regional heterogeneity in the degree of EGFR-GA. When comparing regions with a low densitometric EGFR/interferon (INF) band ratio (< 2.19, n = 18) and a high EGFR/IFN band ratio (> 4.39, n = 14), the latter type of region showed a significantly higher percentage of Ki-67--positive tumor cell nuclei and lower values for several shape variables (Fourier amplitudes), indicating a tendency toward a more regular nuclear shape in regions with distinct EGFR-GA. For the EGFR/IFN band ratio, a significant correlation was found with several morphometric variables, especially those of nuclear shape and distances between nuclei. CONCLUSION: In glioblastomas showing regional heterogeneity in the degree of EGFR-GA, morphology of tumor cell nuclei has been shown to be different when comparing regions with different degrees of EGFR-GA. Glioblastomas may also show distinct regional heterogeneity of histomorphology without evidence of regional heterogeneity of EGFR-GA. A significant statistical association has been confirmed between the degree of EGFR-GA and quantitative morphology of tumor cell nuclei.

Brain Neoplasms↗
PubMed1990

The role of cellular maturation in neutrophil heterogeneity.

Previous studies have shown that many neutrophil (PMN) characteristics are heterogeneous but the origin of PMN heterogeneity is unknown. It is unclear if PMN functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities. The PMN 31D8 antigen is a useful probe for evaluation of PMN subpopulations. The majority of PMNs (approximately 85%) exhibit a high intensity fluorescence after 31D8 monoclonal antibody (MoAb) labeling (31D8 enriched or "bright" PMNs) as determined by flow cytometric analysis. These cells are more functional than cells with low intensity fluorescence (31D8 diminished or "dull" PMNs). Various immunologic, clonogenic and functional techniques were used to study the expression of the 31D8 antigen in HL-60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation. The results of this study indicate that the percentage of 31D8 antigen positive (31D8 antigen enriched and diminished) bone marrow cells increases from 20 +/- 11% in myeloblast cells to 68 +/- 10% in promyelocytes, 93 +/- 2% in myelocytes and 99 +/- 1% in bands and PMNs. 31D8 antigen enriched cells first appear at the myelocyte stage (32 +/- 10%) and increase in bands (52 +/- 13%), marrow PMNs (62 +/- 13%) and peripheral blood PMNs (88 +/- 4%). These data indicate that the heterogeneous expression of 31D8 antigen in PMNs is due, at least in part, to maturational differences within the PMN population and raise the possibility that other heterogeneously expressed PMN characteristics are also maturationally derived. They also suggest that 31D8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology.

Antigens, Surface↗
PubMed1989

Therapeutic implications of tumor heterogeneity.

At the outset of this review, we stated that we wished to raise some questions that challenge the commonly held view that tumor heterogeneity is of major significance to treatment failure. The nature of this challenge is the following: although tumor heterogeneity in sensitivity to therapeutic agents has been demonstrated repeatedly, using isolated subpopulations of cells, primarily in cell culture systems, there is very little work that has been directed toward asking the tough questions about how that heterogeneity actually impacts on the response to treatment in vivo. In our own work, when we have attempted to simulate heterogeneity, in vivo or in vitro with mixed populations of tumor cells, we have seen that the simple prediction that treatment response would reflect the sensitivities of the individual subpopulations was not valid. Tumor subpopulation interactions, influencing both growth and drug sensitivity, resulted in treatment responses that were either better or worse than would be expected. Shifts in the distribution of subpopulations under the influence of therapy did not necessarily correlate with treatment response. Marked differences in the relative proportions of subpopulations within tumors did not necessarily translate into marked differences in the behavior of whole tumors. Imposition of in vivo-like three-dimensional tissue architecture caused major changes in the overall drug sensitivity of individual subpopulations, beyond those seen as a result of heterogeneity. Of course we realize that our work is very limited, one tumor system and a few treatment protocols, but that is the challenge. Much more in-depth experimental and clinical research is necessary in order to evaluate how, and how much, tumor heterogeneity really does affect treatment. Without such work, efforts to devise more effective treatment strategies, based on common assumptions and theoretical models, rather than experimental analysis, can only be superficial and, ultimately, useless.

Animals↗
PubMed1985

The effect of ligand heterogeneity on the Scatchard plot. Particular relevance to lipoprotein binding analysis.

Computer simulations of equilibrium binding studies of a mixture of two labeled ligands binding competitively to a single class of identical and independent sites (receptors) were performed to investigate how ligand heterogeneity affects the observed data in such studies. The simulated data are presented in Scatchard plots. Ligand heterogeneity was generally found to be indistinguishable from the case of a homogeneous ligand when usual experimental conditions applied (that is, Scatchard plots of the data were straight lines). Some factors that increased the probability of recognizing heterogeneity in the system were identified, however. These are 1) a large difference between the dissociation constants of the two ligands, 2) a high concentration of receptors relative to the dissociation constant of the higher-affinity ligand, 3) a high concentration of the lower-affinity ligand relative to that of the higher-affinity ligand, 4) a high specific activity of the lower-affinity ligand relative to that of the higher-affinity ligand, and 5) lack of experimental error. When ligand heterogeneity (under certain conditions) did cause curvilinearity in the Scatchard plot, the curve formed was always concave-downwards. Thus, ligand heterogeneity may occasionally mimic positive cooperativity, but never mimics negative cooperativity or multiple classes of binding sites. Implications of these findings for equilibrium binding studies involving lipoproteins (which are generally isolated as heterogeneous mixtures of particles) are discussed in detail. These findings are also relevant to equilibrium binding studies using ligands which are mixtures of stereoisomers or which contain chemical or radiochemical impurities.

Computers↗
PubMed1986

Heterogeneity of cell surface antigen expression of human small cell lung cancer detected by monoclonal antibodies.

Using immunohistochemistry, radiobinding, and indirect immunofluorescence assays, seven distinct cell surface antigens, detected by monoclonal antibodies, were analyzed for the degree of homogeneity or heterogeneity of antigen expression on a panel of human small cell lung cancers. The panel included 7 tumors taken directly from patients, 21 established cell lines (9 of which were derived from different metastatic sites of 3 patients), and 33 clonal derivatives of 3 lines. With all assays, considerable heterogeneity of antigen expression between tumors from different patients was observed. In both fresh tumors and in cell lines, as well as in cell lines established from different metastatic sites in an individual patient, we observed intratumor heterogeneity finding antigen positive and negative cells and variation in antigenic density, by immunohistochemistry and indirect immunofluorescence assays. Antigenic expression was not cell cycle dependent. In addition, when cell lines or patient samples expressing antigen positive and antigen negative tumor cells were cloned, heterogeneity of antigenic expression was still present in the clonal lines. This suggests that either the expression of the antigen was not heritable and/or the ability to regenerate antigenic heterogeneity is an intrinsic property of the tumor cells. The heterogeneity of antigen expression on lung cancer cells has significant implications for the use of these and other monoclonal antibodies in the study and therapy of lung cancer.

Antibodies, Monoclonal↗
PubMed1986

Genetic heterogeneity among kindreds with Alport syndrome.

Twenty-three kindreds were ascertained through patients at renal clinics at University of Utah Associated Hospitals. Urinalysis indicated glomerulonephritis in 231 of 997 examined kindred members; medical records documented kidney disease consistent with glomerulonephritis in 88 unexamined kindred members. Renal biopsies of 35 persons in a subset of 14 kindreds showed ultrastructural changes and absence of immune phenomena consistent with the diagnosis of Alport syndrome. End-stage renal disease (ESRD) had occurred in 72 (49%) of 148 known affected males and in 13 (8%) of 171 known affected females. No father-son affected pairs occurred in any of the kindreds; 84% of daughters of affected fathers were affected, and 49% of sons and 48% of daughters of affected mothers were affected. One of three phenotypes (juvenile Alport syndrome with deafness, adult Alport syndrome with deafness, or adult Alport syndrome without deafness or other defects) occurred in each of the 23 kindreds. We applied likelihood analysis to test for genetic heterogeneity underlying the phenotypic heterogeneity. In the first application (the admixture test), we tested for the occurrence of two forms of the disease without specifying which kindred had which form; we found insufficient evidence of admixture. In the second application (the predivided-sample test), we tested for genetic heterogeneity expressed as phenotypic heterogeneity. Kindreds were successively divided into two subgroups, with admission to the first subgroup dependent upon: (1) having greater than or equal to 2 males with ESRD, (2) occurrence of deafness in most nephrologically affected male family members, and (3) intrakindred mean age of ESRD in males later than age 31. Weak evidence of heterogeneity was found for category (1); stronger evidence of heterogeneity was found for category (3). Penetrance of microscopic hematuria in female heterozygotes was estimated as 82% overall, 85% for adult Alport syndrome, and 28% for juvenile Alport syndrome.

Deafness↗
PubMed1979

Ontogeny of B-lymphocyte function. IX. Difference in the time of maturation of the capacity of B lymphocytes from foetal and neonatal mice to produce a heterogeneous antibody response to thymic-dependent and thymic-independent antigens.

The ontogeny of the capacity of the B-lymphocyte population to produce a response which is heterogeneous with respect to antibody affinity was studied in a cell transfer system. Lethally irradiated mice were reconstituted with B cells from donors of various ages, together with adult thymus cells when the response to T-dependent antigens was studied. The animals were immunized with one of a variety of antigens one day after cell transfer and the distribution of their splenic plaque-forming cells (PFC) with respect to affinity was assayed, by hapten inhibition of plaque formation, 2 to 3 weeks after immunization. Mice reconstituted with B cells from neonatal donors produced a response of low affinity and restricted heterogeneity. With four different thymic-dependent antigens (DNP-BGG, F-BGG, DNP-KLH and Dan-KLH) the splenic B-cell population acquired the capacity to reconstitute irradiated mice to produce a normal adult-like, highly heterogeneous, high affinity PFC response between 7 and 10 days after birth. The capacity to produce a heterogeneous response to the thymic-dependent protein antigen BGG matured just slightly later between 10 and 14 days of age. The bone marrow matures with regard to the capacity to reconstitute irradiated mice to give a heterogeneous response several days after the spleen, possibly as a consequence of the redistribution of peripheral B cells to the bone marrow. In contrast, maturation of the capacity of the splenic B-cell population to reconstitute irradiated recipients to give a heterogeneous, adult-like PFC response to three 'thymic-independent' antigens (TNP-PA, DNP-Ficoll and TNP-BA) takes place considerably later (between 3 and 4 weeks of age). These results suggest that the population of B-cell precursors which responds to thymic-dependent antigens may represent a different subpopulation of B cells from the population that responds to thymic independent antigens. Furthermore, the results suggest that these B-cell subsets mature at different times, presumably under independent controls.

Age Factors↗
PubMed1982

Heterogeneity of expression and induction of mouse mammary tumor virus antigens in mouse mammary tumors.

Seven spontaneous BALB/cfC3H mouse mammary tumors were heterogeneous in expression of murine mammary tumor virus-associated cell surface antigens. To determine the basis of this heterogeneity, cells from spontaneous tumors and from five subpopulations isolated from a single spontaneous tumor were examined for expression of viral antigens under both conventional conditions and conditions known to induce synthesis of murine mammary tumor virus antigens (5-iodo-2'-deoxyuridine and dexamethasone). Induction with 5-iodo-2'-deoxyuridine resulted in further manifestation of the antigenic heterogeneity of spontaneous tumors. The five subpopulations from a single tumor differed in the amount of viral antigens present in untreated and in induced cultures. Coculturing showed that viral antigen expression was independent in each subpopulation within a heterogeneous mixture and was not influenced by the presence of other subpopulations with different potentials for viral antigen synthesis. The expression of murine mammary tumor virus structural antigens, a protein with a molecular weight of 28,000 and a glycoprotein with a molecular weight of 52,000, differed within the heterogeneous subpopulations, and was noncoordinate. The data suggest that the antigenic heterogeneity in spontaneous tumors reflects the existence of cells within them that differ in both expression of viral antigens and in their response to inducers of viral antigen synthesis.

Animals↗
PubMed1982

Kinetics of the formation of pure and heterogeneous megakaryocyte colonies by megakaryocyte progenitor cells in vitro.

The formation of pure and heterogeneous megakaryocyte colonies in vitro by megakaryocyte progenitor cells was studied using a whole plate stain for acetylcholinesterase to identify megakaryocyte colonies. In cultures of 75,000 C57BL marrow cells, maximal numbers of 11 +/- 5 (mean +/- standard deviation) pure and 6 +/- 1 heterogeneous colonies were reached after 6-7 days of incubation, after which megakaryocyte colony degeneration was marked. The ratio of pure: heterogeneous colonies remained constant at 2:1 both during the incubation period, and when different concentrations of megakaryocyte colony stimulating factor (MEG-CSF) and different numbers of cells per culture were used. The average size of both pure and heterogeneous colonies increased during the incubation period to maximal colony sizes of 15 +/- 13 cells per pure colony and 264 +/- 300 cells per heterogeneous colony. Sequential analysis of individual colonies in situ failed to demonstrate an increase in the size of individual pure colonies, but the enlargement of individual heterogeneous colonies was observed.

Acetylcholinesterase↗
PubMed1981

Kinetics and mechanism of deuterium oxide-induced fluorescence enhancement of fluorescyl ligand bound to specific heterogeneous and homogeneous antibodies.

Comparative kinetics studies of ligand dissociation and D2O enhancement were performed with both heterogeneous and homogeneous anti-fluorescyl immunoglobulin G antibodies. Heterogeneous rabbit and homogeneous mouse (monoclonal) antibody preparations were purified by immunoadsorption and found to be pure IgG by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoelectrophoresis. Relatively high affinities of all liganded antibody preparations were determined by dissociation rate studies, demonstrating comparatively long lifetimes for the dissociation of bound fluorescein. In addition, rabbit anti-fluorescyl preparations were found to display marked heterogeneity of off-rates while mouse monoclonal anti-fluorescyl preparations exhibited a single off-rate indicating homogeneity. D2O fluorescence enhancement studies showed that heterogeneous kinetics was observed with both heterogeneous and homogeneous antibody active sites. Temperature studies of ligand D2O enhancement and dissociation rates using homogeneous anti-fluorescyl antibodies revealed similar, yet different activation energies (22.7 +/- 0.8 cal and 20.2 +/- 0.3 cal, respectively) for both phenomena. The studies demonstrated that the anti-fluorescein antibody active site consists of both solvent accessible and relatively inaccessible components, and that the binding of ligand involves both exchangeable hydrogen atoms and other as yet unresolved interactions. The mechanism of D2O fluorescence enhancement is discussed in terms of its complexity involving heterogeneous rate mechanisms.

Animals↗
PubMed1995

Intratumoral regional heterogeneity of DNA ploidy patterns in colorectal carcinomas.

There is no agreement on the evaluation of intratumoral DNA ploidy heterogeneity, and its clinical significance remains controversial. We categorized intratumoral ploidy heterogeneity in an effort to avoid confusion and misunderstanding among investigators. We classified the heterogeneity into 3 major types (Types A, B and C) and a combined type (Type D), based on the intratumoral distribution profiles of DNA aneuploid lines identified by flow cytometry in 52 cases of colorectal cancer with intratumoral DNA ploidy heterogeneity selected from a consecutive series. Every carcinoma examined in this study fell into one of the 4 categories: Twenty-six tumors (50%) were classified as Type A, 6 (11%) as Type B, 2 (3%) as Type C, and 18 (36%) as Type D. We discussed the mechanisms of DNA ploidy heterogeneity evolution within a tumor, and also proposed a pathway to these types of DNA ploidy heterogeneity as an aid to understanding the relationship between tumor progression and DNA ploidy changes.

Carcinoma↗