Evaluation of Prognostic Factors Following Flow‐Cytometric DNA Analysis after Cytokeratin Labelling: I. Breast Cancer

Wimberger, Pauline; Hillemanns, Peter; Kapsner, Thomas; Hepp, H.

doi:10.1155/2002/630850

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…Another recent paper by Wimberger et al (38), which complied with modern standards, using fresh material and even cytokeratin labeling, showed that ploidy and S‐phase were significant prognostic factors in monovariate analysis, but not in multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

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Flow cytometry in primary breast carcinomas: Prognostic impact of S‐phase fraction according to different analysis patterns

Michels¹,

Marescaux²,

Plancoulaine³

et al. 2004

Cytometry Part B Clinical

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Background: The aim of the present work was to study the prognostic impact of ploidy and S-phase fraction (SPF) assessed according to recently described methods. These methods of analysis combine different ploidy groups and separate euploid (good) prognostic groups from noneuploid (bad) prognostic groups. The definition of euploidy varied according to the author; some of them even included aneuploid peaks with few events. A comparison was also drawn to the average SPF and the diploid peak SPF observed in aneuploid histograms.Methods: From January 3, 1990 to January 7, 1999, 1,984 previously untreated, invasive breast carcinoma samples were snap-frozen and processed for FCM. The present study evaluated all nondiploid and nonmultiploid histograms, using different analysis patterns and the values of the average SPF and diploid SPF.Results: SPF is a salient prognostic factor even after multivariate analysis for DFS and MFS. Using several methods of analysis of ploidy and SPF shows that the classical method of analysis involving separation of ploidy according to diploidy versus aneuploidy and analysis of SPF restricted to the aneuploid peak in nondiploid and nonmultiploid histograms is as relevant as other recently proposed patterns of analysis, and that the average SPF or the diploid SPF of aneuploid tumors does not add significant prognostic information.Conclusions: SPF is a valuable predictor of survival and can be confidently assessed in a simple way by restricting the analysis to the peak of interest (except for multiploid tumors).

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Section: Discussionmentioning

confidence: 99%

“…In Wimberger et al's article (38), no quality control concerning the sample processed, or the histograms or SPF data seems to have been performed. But after contact with the authors, they in fact used analyzable ploidy as an inclusion criterion and performed several quality controls.…”

Section: Discussionmentioning

confidence: 99%

Flow cytometry in primary breast carcinomas: Prognostic impact of S‐phase fraction according to different analysis patterns

Michels¹,

Marescaux²,

Plancoulaine³

et al. 2004

Cytometry Part B Clinical

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“…The prognostic significance of SPF and DNA ploidy in breast cancer following enrichment of tumour cells by cytokeratin labelling has been demonstrated. Univariate analysis in breast cancer detected the prognostic significance of DNA ploidy and SPF of Go/G 1 peak of tumour cells for clinical outcome (49). The SPF is calculated from the ploidy histogram by the use of computer modelling systems to determine the size and the compartment between the G0/G 1 and G 2 /M peaks.…”

Section: S‐phase Fractionmentioning

confidence: 99%

Cell proliferation and cell cycle control: a mini review

Golias

Charalabopoulos

2004

International Journal of Clinical Practice

198

151

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Tumourigenesis is the result of cell cycle disorganisation, leading to an uncontrolled cellular proliferation. Specific cellular processes-mechanisms that control cell cycle progression and checkpoint traversation through the intermitotic phases are deregulated. Normally, these events are highly conserved due to the existence of conservatory mechanisms and molecules such as cell cycle genes and their products: cyclins, cyclin dependent kinases (Cdks), Cdk inhibitors (CKI) and extra cellular factors (i.e. growth factors). Revolutionary techniques using laser cytometry and commercial software are available to quantify and evaluate cell cycle processes and cellular growth. S-phase fraction measurements, including ploidy values, using histograms and estimation of indices such as the mitotic index and tumour-doubling time indices, provide adequate information to the clinician to evaluate tumour aggressiveness, prognosis and the strategies for radiotherapy and chemotherapy in experimental researches.

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“…Fresh tumor tissue of carcinomas of 91 cervical cancers and 73 endometrial carcinomas were dissociated by combined mechanical/enzymatic method [10] as described in detail [11]. The detailed method for evaluation of DNA parameters by DNA flow cytometry was shown elsewhere [12].…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Prognostic Factors Following Flow‐Cytometric DNA Analysis after Cytokeratin Labelling: II. Cervical and Endometrial Cancer

Wimberger

Hillemanns

Kapsner

et al. 2002

Analytical Cellular Pathology

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In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S‐phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC‐conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA‐ploidy nor S‐phase fraction were relevant prognostic parameters. But CV of the G0G1‐peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA‐aneuploidy (DNA‐index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence‐free survival. Especially DNA‐aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA‐ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA‐ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA‐parameters was found.

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Evaluation of Prognostic Factors Following Flow‐Cytometric DNA Analysis after Cytokeratin Labelling: I. Breast Cancer

Cited by 3 publications

References 34 publications

Flow cytometry in primary breast carcinomas: Prognostic impact of S‐phase fraction according to different analysis patterns

Flow cytometry in primary breast carcinomas: Prognostic impact of S‐phase fraction according to different analysis patterns

Cell proliferation and cell cycle control: a mini review

Evaluation of Prognostic Factors Following Flow‐Cytometric DNA Analysis after Cytokeratin Labelling: II. Cervical and Endometrial Cancer

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