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

In gynecologic oncology valid prognostic factors are necessary to estimate the course of disease and to define biologically similar subgroups for analysis of therapeutic efficacy. The presented study is a prospective study concerning prognostic significance of DNA ploidy and S‐phase fraction in breast 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 327 fresh specimens of primary breast cancer. Univariate analysis in breast cancer detected the prognostic significance of DNA‐ploidy, S‐phase fraction and CV (coefficient of variation) of G0G1‐peak of tumor cells for clinical outcome, especially for nodal‐negative patients. Multivariate analysis could not confirm prognostic evidence of DNA‐ploidy and S‐phase fraction. In conclusion, in breast cancer no clinical significance for determination of DNA‐parameters was found.

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Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer

British Journal of Cancer ◽

10.1038/bjc.1992.387 ◽

1992 ◽

Vol 66 (5) ◽

pp. 925-929 ◽

Cited By ~ 28

Author(s):

PD Stanton ◽

TG Cooke ◽

SJ Oakes ◽

J Winstanley ◽

S Holt ◽

...

Keyword(s):

Breast Cancer ◽

Dna Ploidy ◽

Prognostic Significance ◽

S Phase ◽

Phase Fraction

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Breast cancer: prognostic significance of c-erb-B2 and int-2 amplification compared with DNA ploidy, S-phase fraction, and conventional clinicopathological features

Breast Cancer Research and Treatment ◽

10.1007/bf00666477 ◽

1994 ◽

Vol 29 (3) ◽

pp. 237-245 ◽

Cited By ~ 16

Author(s):

Ulf L�nn ◽

Sigrid L�nn ◽

Bo Nilsson ◽

Bj�rn Stenkvist

Keyword(s):

Breast Cancer ◽

Dna Ploidy ◽

Prognostic Significance ◽

S Phase ◽

Clinicopathological Features ◽

Phase Fraction

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Lack of prognostic significance of DNA Ploidy and S phase fraction in human breast cancer

The Breast ◽

10.1016/0960-9776(92)90178-5 ◽

1992 ◽

Vol 1 (3) ◽

pp. 148

Author(s):

PD Stanton ◽

SJ Oakes ◽

GD Murray ◽

TG Cooke

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Dna Ploidy ◽

Prognostic Significance ◽

S Phase ◽

Phase Fraction ◽

Human Breast

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

Analytical Cellular Pathology ◽

10.1155/2002/346969 ◽

2002 ◽

Vol 24 (4-5) ◽

pp. 147-158 ◽

Cited By ~ 9

Author(s):

Pauline Wimberger ◽

Peter Hillemanns ◽

Thomas Kapsner ◽

Hermann Hepp ◽

Rainer Kimmig

Keyword(s):

Cervical Cancer ◽

Endometrial Cancer ◽

Prognostic Factors ◽

Endometrial Carcinoma ◽

Dna Ploidy ◽

S Phase ◽

Phase Fraction ◽

Dna Aneuploidy ◽

Flow Cytometric

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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Optimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimens

Cytometry ◽

10.1002/cyto.1097 ◽

2001 ◽

Vol 46 (3) ◽

pp. 121-135 ◽

Cited By ~ 34

Author(s):

C.B. Bagwell ◽

G.M. Clark ◽

F. Spyratos ◽

A. Chassevent ◽

P.-O. Bendahl ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Markers ◽

Dna Ploidy ◽

S Phase ◽

Phase Fraction ◽

Node Negative ◽

Flow Cytometric ◽

Node Negative Breast Cancer

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DNA ploidy and percent S-phase as prognostic factors in node-positive breast cancer: results from patients enrolled in two prospective randomized trials.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.2.351 ◽

1993 ◽

Vol 11 (2) ◽

pp. 351-359 ◽

Cited By ~ 24

Author(s):

T E Witzig ◽

J N Ingle ◽

D J Schaid ◽

L E Wold ◽

J F Barlow ◽

...

Keyword(s):

Breast Cancer ◽

Flow Cytometry ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Dna Ploidy ◽

Univariate Analysis ◽

S Phase ◽

Node Positive ◽

Significant Difference ◽

Positive Breast Cancer

PURPOSE AND METHODS To help clarify the clinical utility of flow-cytometric parameters, we performed flow cytometry on archival paraffin-embedded primary breast cancers from 502 patients treated on two adjuvant chemotherapy protocols performed by the North Central Cancer Treatment Group (NCCTG) and Mayo Clinic. DNA ploidy and percent S-phase (%S) were examined in univariate and Cox model multivariate analyses along with tumor size, menopausal and estrogen receptor status, Quetelet's index (QI), number of positive nodes and nodes examined, and Fisher and nuclear grades. RESULTS Ploidy analysis showed that 40% of tumors were DNA diploid and 60% were DNA nondiploid (12% tetraploid and 48% aneuploid). There was no difference in relapse-free survival (RFS) (P = .82) or overall survival (OS) (P = .78) between the ploidy groups. Tetraploid patients had the longest RFS and OS of any group, but this did not achieve statistical significance. The %S was computed in 98% of cases and the medians were 9.0% for all patients, 6.4% for diploid patients, and 11.7% for nondiploid patients (P < .0001). By use of a %S greater than 12.3 as a prognostic variable in a univariate analysis, there was a significant difference in the RFS (P = .02) and OS (P = .007) of patients with low- versus high-proliferative tumors. However, when the %S was adjusted for clinical characteristics in the multivariate analysis, it was not a significant factor for RFS (P = .23) or OS (P = .36). CONCLUSION These results indicate that DNA content and %S measurements by flow cytometry are not clinically useful independent prognostic factors in women with resected node-positive breast cancer administered adjuvant chemotherapy.

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