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

2002 ◽  
Vol 24 (4-5) ◽  
pp. 147-158 ◽  
Author(s):  
Pauline Wimberger ◽  
Peter Hillemanns ◽  
Thomas Kapsner ◽  
Hermann Hepp ◽  
Rainer Kimmig

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.


2019 ◽  
Vol 29 (2) ◽  
pp. 305-311
Author(s):  
Teresia Svanvik ◽  
Ulf Strömberg ◽  
Erik Holmberg ◽  
Janusz Marcickiewicz ◽  
Karin Sundfeldt

ObjectivesTo assess the effects on relative survival of established and new prognostic factors in stage I–III grade 1–3 endometrioid endometrial carcinoma and in the subgroup of stage I grade 1–2.MethodsThis was a population-based, retrospective study including all women (n=1113) in the western Swedish healthcare region diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I–III grade 1–3 endometrioid endometrial carcinoma in 2006–2011. Histology, grade, stage, and age were prospectively reported to the regional clinical and national cancer registers. DNA ploidy and S-phase fraction were analyzed by flow cytometer. S-phase fraction cut-off was set at ≥8%. Tumor biopsies were classified as diploid if there was one G0/G1 peak or the DNA index was 1.0±0.04. Overexpression of p53 as determined by immunohistochemistry was positive if strong nuclear staining was found in >30% of the neoplastic cells.ResultsBased on univariable statistical analyses we found that 5-year relative survival was significantly associated with S-phase fraction, DNA ploidy, p53, stage, grade, and age. Excess mortality for S-phase fraction ≥8%, aneuploidy, and p53 overexpression was 8, 14, and 8 and times higher, respectively. However, in a multivariable regression model, adjusted for stage, grade, and age, S-phase fraction, DNA ploidy, and p53 were not statistically independent prognostic factors (p=0.413, p=0.107, p=0.208, respectively) for 5-year relative survival in stage I–III grade 1–3 endometrioid endometrial carcinoma. In a subgroup analysis of stage I grade 1–2, aneuploidy identified a subgroup with impaired 5-year relative survival.ConclusionWe can conclude that S-phase fraction, DNA ploidy, and p53 overexpression did not improve identification of high-risk patients by stage, grade, and age in stage I–III endometrioid endometrial carcinoma. In stage I, aneuploidy and grade 2 predicted lower relative survival rates than other variables.



2002 ◽  
Vol 24 (4-5) ◽  
pp. 135-145 ◽  
Author(s):  
Pauline Wimberger ◽  
Peter Hillemanns ◽  
Thomas Kapsner ◽  
Hermann Hepp ◽  
Rainer Kimmig

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.



1997 ◽  
Vol 40 (4) ◽  
pp. 411-419 ◽  
Author(s):  
António E. Pinto ◽  
Paula Chaves ◽  
Paulo Fidalgo ◽  
António G. Oliveira ◽  
Carlos N. Leitøo ◽  
...  


1995 ◽  
Vol 58 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Jacobus Pfisterer ◽  
Friedrich Kommoss ◽  
Willi Sauerbrei ◽  
Ina Rendl ◽  
Marion Kiechle ◽  
...  


1991 ◽  
Vol 64 (3) ◽  
pp. 578-582 ◽  
Author(s):  
T Visakorpi ◽  
O-P Kallioniemi ◽  
IYI Paronen ◽  
JJ Isola ◽  
AI Heikkinen ◽  
...  


1998 ◽  
Vol 16 (4) ◽  
pp. 223-231 ◽  
Author(s):  
Mar Abad ◽  
Juana Ciudad ◽  
Manuel R. Rincon ◽  
Isabel Silva ◽  
José I. Paz-Bouza ◽  
...  

In the present study the prognostic value of both DNA ploidy and the proliferative activity of tomour cells were studied in a series of 76 consecutive patients suffering from gastric tumours. DNA ploidy and the proliferative index (as measured by the percentage of S-phase cells) were determined by flow cytometry using fresh tumour specimens.The presence of DNA aneuploid clones by flow cytometry was detected in 62% of the cases (mean DNA index of 1.63 ± 0.46; range 1.08–2.92), the mean proportion of S-phase cells being of 18.4 ± 11.5%. In comparison with diploid cases, aneuploid tumours showed a higher proliferative activity (cases with more than 15% S-phase cells: 18.4% versus 6.1%,p= 0.0001) as well as a higher incidence of node involvement (95% versus 68%,p= 0.001). By contrast, no significant differences were detected with respect to sex, age, histologic grade and type, clinical stage, tumour size and the incidence of extranodal involvement.Upon grouping the patients according to the proportion of S-phase cells no significant differences were observed for the clinical and biological parameters explored except for an association between a high percentage of S-phase cells and the presence of DNA aneuploidy (40% versus 96%,p= 0.0001). Regarding survival the presence of DNA aneuploidy was significantly associated with poor outcome as compared to the diploid cases (median of 15 versus 26 months,p= 0.005). By contrast, the proportion of S-phase cells did not predict patients’s outcome.Multivariate analysis of prognostic factors showed that the presence of DNA aneuploidy (p= 0.003) together with the histologic type (p= 0.03) and the existence of extranodal metastases (p= 0.05) were the best combination of prognostic factors for survival prediction.



1995 ◽  
Vol 71 (1) ◽  
pp. 177-181 ◽  
Author(s):  
M Karlsson ◽  
B Boeryd ◽  
J Carstensen ◽  
B Kågedal ◽  
S Wingren


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