Heterogeneity of DNA Ploidy in Endometrial Carcinoma: Comparison of Different Tissue Samples Obtained during Diagnosis and Treatment

Aim: Comparison of DNA ploidy status of different tumour tissue samples (fresh/frozen vs. paraffin-embedded; curettage vs. hysterectomy samples) obtained during diagnosis and treatment of patients with endometrial carcinoma. Patients and Methods: DNA ploidy status and conventional prognostic parameters were recorded for 74 patients with endometrial carcinoma prospectively. Results: In 59 (79.7%) patients the DNA status was described as diploid in all analyzed tissue samples. The remaining 15 (20.3%) cases were described as DNA aneuploid in at least one of the corresponding tissue samples. The concordance between DNA ploidy status in fresh vs. paraffin-embedded hysterectomy samples as well as curettage vs. hysterectomy paraffin-embedded samples was high (kappa coefficient κ=0.6348, 95% confidence interval CI=0.3673-0.9023, and p=0.6408, 95% CI=0.3977-0.8838), however, the methods are not interchangeable. Conclusion: The DNA ploidy discordance observed in our study group seems to document intratumoral heterogeneity that should be expected when applying DNA ploidy status in the clinical management of endometrial carcinoma. Endometrial carcinoma (ECA) is the most common gynaecologic malignancy in the Western world. Approximately 80% of cases are diagnosed at an early stage, being well to moderately differentiated at the time of diagnosis. Due to the high cure rate, the survival of patients with ECA is generally good. The overall 5-year relative survival rate is 84% (96% for stage I, 68% for stage II and III, 17% for stage IV, respectively (1). The key prognostic parameters are International Federation of Gynecology and Obstetrics (FIGO) stage, grade, histologic subtype, depth of myometrial invasion, vascular invasion and lymph node metastases. However, none of these conventional prognostic factors allows selection of all patients with poor prognosis. Additional parameters related to high risk of recurrence or death from the disease are under investigation. Immunohistochemical examination of molecular, biological markers and DNA ploidy are in the focus of research for ECA prognostic parameters. DNA aneuploidy is related to more advanced disease at diagnosis and high risk of recurrence, and consequently to significantly lower overall survival of patients with ECA (2-4). Even patients with disease of the same stage and grade have worse survival if DNA aneuploidy is found as compared to DNA diploidy (5-7). In most studies, DNA ploidy has been found to be a stronger prognostic factor than any other tumour-associated parameter, with the possible exception of p53 overexpression (8). The aim of this study was to compare the DNA ploidy status in different tissue samples obtained during diagnosis and treatment of patients with ECA. We analyzed tissue samples from pre-treatment biopsy (curettage or hysteroscopy) and primary surgery (hysterectomy) with different time of sample collection. Usually it takes from 2 to 4 weeks from pre-treatment biopsy to surgical therapy, the most frequent primary treatment in patients with ECA. Regarding the specimen category, formalin-fixed paraffin- embedded (FFPE) and fresh/frozen samples were analyzed; samples differ substantially in the sampling method