Ten‐year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma

Abstract

BACKGROUND.To improve the outcome of endometrial cancer patients, a more accurate prognostic assessment is mandatory. The aims of the study were to evaluate the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with endometrial cancer and to verify if ploidy was able to distinguish patients with different prognosis into homogeneous subgroups for grade of differentiation and stage.METHODS.In a prospective study, DNA ploidy was evaluated from fresh tumor samples in 174 endometrial cancer patients who underwent surgery as the first treatment. Ploidy, as well as classical parameters, were analyzed in relation to the length of disease‐free survival and disease‐specific survival.RESULTS.DNA aneuploidy was found in 49 patients (28.2%). Patients with DNA‐aneuploid tumors had a significantly reduced disease‐free interval and disease‐specific survival (P < .0001). The 10‐year survival probability was 53.2% for DNA‐aneuploid patients and 91.0% for patients with DNA‐diploid tumors. By multivariate analysis DNA‐aneuploid type was the strongest independent predictor of poor outcome, followed by age and stage. Patients with DNA‐aneuploid tumor had a significantly higher risk ratio for recurrence (5.03) and death due to disease (6.50) than patients with DNA‐diploid tumors. Stratification by DNA‐ploidy within each group by grade of differentiation allowed identification of patients with significantly different outcome. In grade 2 tumors, 10‐year survival was 45.0% in aneuploid cases and 91.9% in diploid cases (P < .0001). Patients with advanced‐stage (>I) diploid tumor did significantly better than patients with stage I aneuploid tumor (P = .04).CONCLUSIONS.The presence of DNA‐aneuploid type in endometrial cancer identifies high‐risk cases among the patients considered ‘low risk’ according to stage and grade of differentiation. Cancer 2007. © 2007 American Cancer Society.

Microsatellite instability and ploidy status define three categories with distinctive prognostic impact in endometrioid endometrial cancer

“…MSS-aneuploid subtype tumors had pathological features similar to those of MSI tumors, since they frequently presented higher grade, advanced stage and vascular involvement. The association of aneuploidy with a more aggressive clinical phenotype in EC is well documented [4, 27, 28]. According to our data, MSS-diploid tumors display a more benign phenotype (differentiated grade, early stage and absence of vascular invasion) compared to MSI and MSS-aneuploid tumors.…”

“…Conversely, several groups have referred an association of MSI with better [23, 24], or worse [25] outcome in series including only endometrioid tumors or both histological types. As for the prognostic value of ploidy in EC, latest publications suggest that is a statistically independent prognosticator of poor outcome through multivariate analysis [4, 27, 28]. …”

“…Type II non endometrioid EC (mostly papillary serous and clear cell), commonly occurs in older women with a background unrelated to unopposed estrogen exposure, usually is high grade and has worse prognosis [2, 3]. The endometrioid type frequently presents microsatellite instability (MSI), estrogen (ER) and progesterone (PR) receptors expression, PTEN , K-ras and β-Catenin mutations, epigenetic silencing of APC and a near diploid DNA content, although aneuploidy has also been detected in around 20% of this type [4]. In contrast, the non endometrioid type is mostly aneuploid, with lack or weak ER and PR expression, p53 mutations and HER2 overexpression [2, 3].…”

“…Published data about the clinical impact of MSI are conflicting [21-26], and recent studies have related aneuploidy to worse clinical behavior [4, 27, 28]. …”

Uterine Papillary Serous, Clear Cell, and Poorly Differentiated Endometrioid Carcinomas: A Comparative Study

“…18,22,23 It has been claimed that DNA ploidy is one of the strongest prognosticators in endometrial cancer. 24,25 DNA aneuploid tumors are significantly more frequent in elderly, poorly differentiated and advanced disease patients. In the present series, although DNA ploidy was assessed in 62% of cases, aneuploidy was significantly more frequent in the UPSC/CC subgroup than in PDEC.…”