Intratumoral variations in dna distribution patterns in mammary adenocarcinomas

Askensten, U; Rosen, Anette K. Von; Nilsson, Roland; Auer, Gert

doi:10.1002/cyto.990100312

Cited by 41 publications

(19 citation statements)

References 25 publications

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“…Some studies have demonstrated that intratumor heterogeneity may exist in some types of tumors, particularly in breast cancers (16)(17)(18)(19). DNA content heterogeneity within individual tumors has also been reported in colonic adenocarcinoma (201, lung cancers (21), transitional cell cancers of the bladder (23, and prostatic adenocarcinomas (23).…”

Section: Samplingmentioning

confidence: 99%

Guidelines for implementation of clinical DNA cytometry

Shankey

Rabinovitch

Bagwell³

et al. 1993

Cytometry

373

173

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Cell DNA content measurements, including determination of tumor ploidy and S-phase fraction, have been performed on a wide variety of human tumors for > 20 years using flow cytometry. During this time many publications have discussed the clinical utility of cell DNA content measurements. A major impediment to the more widespread application of cytometric DNA content measurements has been the lack of agreement among these studies. Whereas some discrepancies can be attributed to poorly designed studies lacking sufficient follow-up or significant numbers of patients, in many cases the discrepancies are due to technical factors in flow or image cytometry.The terminology used to describe the results of flow cytometry studies is often confusing and not universally applied. Although a convention for nomenclature for all DNA cytometry was recommended in 1984 (l), the guidelines suggested are frequently not used in published studies. Cytometric studies should not use cytogenetic terminology (hypodiploid, peritetriploid, etc.), where no direct measurement of changes in the number or composition of individual chromosomes has been made. Rather, the terms DNA diploid and DNA aneuploid should be used, with identification of the degree of DNA content abnormality given by the use of the DNA index, or DI (ratio of mean or mode of sample G,/G, population divided by mean or mode of diploid reference cells).One critical aspect of the clinical applications of these measurements is the use of standardized procedures to prepare and analyze clinical samples and to analyze and interpret cytometry data. A number of studies have demonstrated significant intralaboratory, as well as interlaboratory variation in the results of DNA content analyses (2-5) and in the interpretation of flow cytometric data (6). The purpose of this work is to help increase the reliability and reproducibility of DNA content flow cytometry by pointing out important technical considerations for cytometry, to provide guidelines that logically follow from these considerations, and to provide a framework for the development of standards and standardization of DNA content flow cytometry. Although a number of reported studies have utilized image cytometry to provide DNA content analysis, the technical differences between image and flow cytometry suggest that guidelines for the clinical application of image cytometry be developed independently.In reviewing the published literature, it is clear that many studies fail to provide sufficient information to judge critically the quality of cytometric measurement. It is recommended that all publications using DNA content cytometry provide details of the technique used to isolate and prepare cells, data that indicate that the sample used for cytometry contains representative tumor material, details concerning the techniques used to stain cells or nuclei (dye concentration, enzyme concentrations in units, cell concentrations), and details of the techniques used to analyze DNA content histograms (debris and aggregation correction ...

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Section: Samplingmentioning

confidence: 99%

Guidelines for implementation of clinical DNA cytometry

Shankey

Rabinovitch

Bagwell³

et al. 1993

Cytometry

373

173

View full text Add to dashboard Cite

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“…In the following, the tubular and tubuloductal carcinomas are abbreviated TD, followed by + sign(s) or 0, whereas ductal carcinomas of comedo type are abbreviated comedo. In parallel with the morphological assessment, the amount of non-cancerous cells (mesenchymal tissue), as a proportion of the total cell content, was recorded, the results being divided into four groups (1)(2)(3)(4): group 1, 0-25%; group 2, 26-50%; group 3,51-75%; and group 4, 76-100%.…”

Section: Histopathology (4-biopsy Series Only)mentioning

confidence: 99%

One or multiple samplings for flow cytometric DNA analyses in breast cancer‐prognostic implications?

Fernö¹,

Baldetorp²,

Ewers³

et al. 1992

Cytometry

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Flow cytometric assessments of DNA ploidy status and the S-phase fraction (SPF) have been shown to yield prognostic information in breast cancer. The aim of the present investigation was to elucidate the reproducibility of results with regard to tumor DNA heterogeneity, and to ascertain whether the prognostic value of DNA measurements might be enhanced by analyzing two pieces of a tumor instead of one.Agreement with regard to ploidy status (diploid versus non-diploid) was obtained in 90% of cases (71/79) when two adjacent sections of the tumor were investigated, and in 77% of cases (10/13) when four biopsies from different quadrants of the tumor specimen were investigated. The corresponding figures for agreement in SPF (divided into three categories, < 7.0%, 7.0-11.9%, and > 12%) were 75% 69/79; 2-sample series) and 55% (7/13; 4-biopsy series).The main reason for variance in ploidy results was the difficulties in distinguishing near diploid cell populations. Discrepancies in SPF categories could be explained by minor fluctuations in SPF values near the cut-off levels, or by variance in ploidy status, the fraction of nondiploid nuclei, and background noise due to cell debris.There was a stepwise increase in recurrence rate (RR) among patients with increasing SPF category (RR: 20%, 41%, and 53%). Patients whose SPF categories varied, from low or intermediate in one part of the tumor to high in another, seemed to have a poor prognosis (RR = 57%).We conclude that the variation in ploidy status and SPF between different parts of the same tumor specimen is largely to be explained by uncertainty in the interpretation of the DNA histograms and by difficulties inherent in the estimation of SPF, rather than by the existence of DNA tumor heterogeneity. Evaluation of a different part of the same tumor specimen may be of value, especially in the case of SPF, as this may yield additional prognostic information. These findings also emphasize the need for good quality control of FCM DNA analysis.

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“…However, in other studies where the DNA ploidy of specimens from different areas of resected tumours were compared, only small differences between the samples were seen. It was concluded that different results are not likely to be attributed to intratumoral DNA heterogeneity but to differences in the methods used [37,38]. In the present study, a flow cytometric method for routine determination of the DNA ploidy of cells obtained by forceps biopsies from patients with oesophageal cancer was developed.…”

Section: Representativeness Of Forceps Biopsiesmentioning

confidence: 99%

Development of a Flow Cytometric Method to Determine DNA Ploidy of Oesophageal Cancer Cells Obtained by Forceps Biopsy Samples During Oesophago-Gastro-Duodenoscopy

Rickes¹,

Hauptmann

Flath³

et al. 2003

Oncol Res Treat

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Background: The DNA content of oesophageal tumour cells is a prognostic factor in untreated patients. To investigate whether DNA ploidy is useful to select patients for neoadjuvant therapy it is of interest to develop a method allowing reliable flow cytometric analysis of the DNA content of tumour cells obtained by forceps biopsy during endoscopy before start of therapy. Methods: Freshly frozen forceps biopsy samples from 30 patients with oesophageal cancer were disaggregated. DNA was stained with propidium iodide and ploidy was determined by flow cytometry. To enhance sensitivity epithelial cells were simultaneously labelled with anti-cytokeratin antibodies. Results were compared with image analysis. To evaluate the sampling error, parallel measurements were done in 10 patients by image analysis on forceps biopsies obtained during endoscopy before surgery and on the resected tumour. Results: The sensitivity to detect aneuploidy was lower for standard flow cytometry than for image analysis (13 versus 33%). The overall sensitivities were identical using a double labelling technique with additional cytokeratin-staining of the epithelial cells, but divergent results were obtained in 2 cases, where detection of aneuploidy was either possible with image analysis or with double labelling flow cytometry only. DNA content of samples gained by forceps biopsies and surgically resected tumours was concordant in 8 of 10 cases. In 2 patients, aneuploidy was detected only in the surgically resected tumour but not in the pre-operatively obtained forceps biopsies. Conclusions: A flow cytometric method for routine determination of the DNA ploidy of cells obtained by forceps biopsies from patients with oesophageal cancer was developed and evaluated against image analysis. The technique allows the prediction of DNA content before tumour resection, and might be used for optimising therapy and the patient’s quality of live.

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Intratumoral variations in dna distribution patterns in mammary adenocarcinomas

Cited by 41 publications

References 25 publications

Guidelines for implementation of clinical DNA cytometry

Guidelines for implementation of clinical DNA cytometry

One or multiple samplings for flow cytometric DNA analyses in breast cancer‐prognostic implications?

Development of a Flow Cytometric Method to Determine DNA Ploidy of Oesophageal Cancer Cells Obtained by Forceps Biopsy Samples During Oesophago-Gastro-Duodenoscopy

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