Deoxyribonucleic acid ploidy in endometrial carcinoma: a reproducible and valid prognostic marker in a routine diagnostic setting
ABSTRACT The objective of the study was to investigate the prognostic impact of deoxyribonucleic acid (DNA) ploidy in endometrial carcinoma in a routine diagnostic series as compared with a research series.
We studied a population-based series of 363 endometrial carcinomas prospectively collected, with long and complete follow-up. The prognostic value of DNA ploidy was investigated in a routine diagnostic series (n=262) and compared with the results from a previous research series (n=101).
The proportion of DNA aneuploid tumors was 21% in the research series and 25% in the routine diagnostic series (P=NS). In both series, DNA aneuploidy was significantly correlated to higher age at diagnosis, nonendometrioid subtype, and high histologic grade. Patients with DNA aneuploid tumors had significantly poorer survival, adjusted for established clinicopathologic prognostic factors.
DNA ploidy estimation in endometrial carcinoma adds independent prognostic information in a routine diagnostic setting.
SourceAvailable from: Sergio Alonso[Show abstract] [Hide abstract]
ABSTRACT: Microsatellite instability (MSI) and aneuploidy are inversely related phenomena. We tested whether ploidy status influences the clinical impact of MSI in endometrioid endometrial cancer (EEC). We analyzed 167 EECs for MSI and ploidy. Tumors were classified in three categories according to MSI and ploidy status. Associations with clinicopathological and molecular variables, survival, and treatment response were assessed. All MSI tumors (23%) were scored as diploid, and 14% of microsatellite stable (MSS) tumors presented aneuploidy. MSI tumors associated with older age at diagnosis, non-obesity, high histological grade, and advanced surgical stage. MSS-aneuploid tumors also associated with higher grade and advanced stage. In multivariate survival analysis MSI did not influence disease-free survival (DFS) or cancer-specific survival (CSS). However, when just diploid tumors were considered for the analysis, MSI significantly contributed to worse DFS and CSS, and the same was observed for aneuploidy when MSS tumors were analyzed alone. In diploid tumors, a differential response to postoperative radiotherapy (RT) was observed according to MSI, since it predicted poor DFS and CSS in the multivariate analysis. We conclude that ploidy status influences the clinical impact of MSI in EEC. Among diploid tumors those with MSI have poor clinical outcome and respond worse to RT.Oncotarget 07/2014; 5(15). · 6.63 Impact Factor
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ABSTRACT: Objective. This study assesses the role of preoperative serum CA125 levels in the planning treatment options for women diagnosed with uterine cancer. Material and Method. Ninety five consecutive patients diagnosed with uterine cancer during a four-year period were identified. Age ranged from 35 to 89 years with a mean age of 69 years. The preoperative CA125 levels were dichotomised at 28 U/mL (using ROC analysis to identify the best discriminating threshold for 5-year survival). This level was then correlated with preoperative prognostic indicators: patient age, tumour grade, and histopathological tumour cell type. Survival data was plotted using Kaplan-Meier curves and analysed using the log-rank test. Univariate and multivariate analysis were performed to identify the predictors of overall survival. Results. The mean age of patients was 69 years (range: 35-89). On univariate analysis, the use of preoperative CA125 levels of greater or less than 28 U/mL correlated significantly with age (P = 0.01), the grade of disease (P = 0.02) and unfavourable tissue type (P = 0.03). This threshold CA125 level had a sensitivity of 75%, specificity of 76%, positive predictive value of 35% and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for predicting nodal disease. Using a threshold of preoperative CA125 level of 28 U/mL (area under curve: 0.60) was also a significant predictor of 5-year survival (log-rank test, P = 0.01). Using Cox multivariate survival analysis to identify predictive preoperative factors overall, unfavourable cell type was the strongest predictor of survival (Chi square = 36.5, df = 4, and P = 0.001), followed by preoperative CA125 level (CA125 > 28 U/mL, P = 0.011) and unfavourable preoperative grade (P = 0.017). Amongst patients with a favourable histological tissue type (endometrioid), preoperative CA125 levels predicted overall survival (Chi square = 6.039, df = 2, P = 0.02); however unfavourable preoperative grade did not (P = 0.5). Overall, at five-year follow-up, while there were no deaths among the women with preoperative serum CA125 less than 12 U/mL, eleven of the twenty-three deaths (47.82%) in the study occurred in women with a preoperative CA125 more than 28 U/mL. Conclusions. A preoperative CA125 assay for women with uterine cancer is a relatively inexpensive, reproducible, and objective test which provides valuable information regarding the risk of metastatic disease and overall likelihood of long term survival. Patients with a low likelihood of metastatic/nodal disease (favourable tissue type and CA125 level < 28 U/mL) and significant comorbidities may benefit from avoiding an extended complete staging procedure. Alternatively, a high level of CA125 may prompt further imaging and multidisciplinary discussions to plan for individualised management and consideration for recruitment to clinical trials.01/2014; 2014:497478. DOI:10.1155/2014/497478
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ABSTRACT: In spite of the high and increasing incidence of endometrial cancer, our current models for prediction of prognosis and even more treatment response are suboptimal, and molecular biomarkers to assist clinical decision making are needed. In this review an overview is given of the currently known as well as promising prognostic and predictive biomarkers in endometrial carcinoma. Key clinical challenges, where use of molecular biomarkers can meet clinical needs, are highlighted. The current status for the presently most promising prognostic and predictive biomarkers in endometrial carcinoma is reviewed. DNA ploidy, p53 status, hormone receptor level, HER2, stathmin, L1 cell adhesion molecule expression and other biomarkers are discussed in relation to the scientific robustness of various essential steps in biomarker development and (current) clinical applicability for individualizing treatment strategies. Tumour heterogeneity and its consequences for biomarker assessment and the importance of developing standardised tests for implementation are discussed. To improve the development and clinical uptake of biomarkers, several strategies are proposed.Current Oncology Reports 09/2014; 16(9):403. DOI:10.1007/s11912-014-0403-3 · 2.87 Impact Factor