Abstract
Cancer of the corpus uteri remains the most common gynecological related cancer in developed countries. Cytology, after the induction of liquid based cytology, has reemerged as a possible first line non-interventional diagnostic procedure with promising results. Apart from slide preparation for cytology diagnosis, LBC allows the application of elaborate molecular tests on the residual material. Samples from 74 symptomatic women were collected in ThinPrep PreservCyt medium, from witch immunocytochemical and molecular tests were performed. Final diagnosis of 39 endometrioid carcinomas, 20 non-endometrioid carcinomas and 15 non-malignant was set after hysterectomy. Topoisomerase IIa expression was common (42%) in both types of cancer. Promoter methylation analysis revealed that hMLH1 is commonly methylated in cancers (52.7%), CDKN2A and MGMT less often (27.1%) and RARB rarely methylated (8.4%). BRAF activating mutation V600E was a rare event (8.4%) only found in low grade endometrioid carcinomas. Topoisomerase IIa expression correlated with BRAF mutations, hMLH1 and to lesser extent with CDKN2A methylation. Almost none of the biomarkers were positive in cytological negative or hyperplastic without atypia samples. Detection of methylation in any gene displayed sensitivity, specificity, PPV and NPV similar to cytology of cancer. However, inclusion of cytology diagnosis of hyperlasias with atypia increased sensitivity and NPV of cytology outperforming methylation of any gene. Further evaluation of the panel of promoter methylation, especially in cytology diagnoses of hyperplasia with or without atypia should be evaluated since initial results are promising. Even though methylation of MGMT and RARB are rare events, some patients could be benefit from specific chemotherapeutics that target either of them or the more frequently expressed topoisomerase IIa.
Highlights
Cancer of the corpus uteri remains the most common gynecological related type of cancer in developed countries, while it is outnumbered only by cervix uteri cancer in developing countries due to lack of screening programs [1]
Most endometrial carcinomas are presented with abnormal uterine bleeding and less than 1% are asymptomatic [14]
The most common type was endometrioid carcinoma, as expected, with the majority of them being of grade I or II
Summary
Cancer of the corpus uteri remains the most common gynecological related type of cancer in developed countries, while it is outnumbered only by cervix uteri cancer in developing countries due to lack of screening programs [1]. The increase in endometrial carcinomas observed in developed countries has been linked to increased life expectancy, obesity and tamoxifen use [2,3]. Type I, which accounts for 70% - 80% of endometrial carcinomas, include grade I and II endometrioid adenocarcinomas, that are considered to be low grade, are usually hormone-dependent and more often in pre- or peri-menopausal women [11]. The less common type II, on the other hand, includes grade III endometrioid and all non-endometrioid carcinomas (clear cell, serous, mixedtype carcinomas and carcinosarcomas), are non-hormone dependent and usually found in post-menopausal women [11].
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