title: Ploidy and S-phase fraction as predictive markers of response to radiotherapy in cervical cancer.
abstract: The aim of this study was to investigate the potential clinical utility of DNA flow cytometry biomarkers, ploidy, and S-phase fraction (SPF) in predicting overall survival in cervical cancer. This prospective study involved 159 patients with cervical carcinoma (median follow-up, 48 months). Pretreatment clinical staging was done according to the FIGO 2009 update classification. Biopsy tumor samples were used for flow cytometry analysis and histological examination. A prognostic study was performed using both Cox and Bayesian Weibull regression models. Eighty (50.3%) tumors presented DNA aneuploidy, mostly observed in adenosquamous (AS) cell carcinoma (8 of 9 cases) and adenocarcinoma (AC) (12 of 17 cases). The median SPF value (8.6%) was used for discriminating low vs. high tumor cell proliferation. High SPF significantly correlated with aneuploidy (p<0.001). All AS carcinomas had SPF>15%, while all ACs presented SPF<10% (p<0.001). Forty-three (27%) patients died of the disease during follow-up. Log-rank tests revealed significant differences between survival curves for older patients (≥44 years) (p=0.029), advanced clinical staging (p<0.001), and DNA diploidy in stage IIB of disease (p=0.039). Both regression analyses showed that advanced clinical staging and low SPF independently predict worse overall survival of patients. The results suggest that DNA flow cytometry parameters can provide additional predictive information in cervical cancer management.
authors.affiliation: Serviço de Anatomia do Instituto Português de Oncologia de Lisboa, Portugal. yasemin.goksu@gmail.com
authors.forename: António E
authors.initials: AE
authors.lastname: Pinto
authors.forename: Ausenda
authors.initials: A
authors.lastname: Pires
authors.forename: Giovani
authors.initials: G
authors.lastname: Silva
authors.forename: Clara
authors.initials: C
authors.lastname: Bicho
authors.forename: Saudade
authors.initials: S
authors.lastname: André
authors.forename: Jorge
authors.initials: J
authors.lastname: Soares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008940:Mitotic Index; D009367:Neoplasm Staging; D011003:Ploidies; D016016:Proportional Hazards Models; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor