Predictive factors of endometriosis progression into ovarian cancer

Background In recent years, the endometriosis has overcome a noteworthy renaissance in the recognition of its potential. In certain patients, a demonstrable malignant progression of ectopic foci leading to development of ovarian cancer is seen. The knowledge of endometriosis overthrow background into endometriosis associated ovarian cancer is of paramount importance for selection of patients at risk. The goal of the presented study was to review a malignant potential of the endometriosis and to specify predictive factors of endometriosis progression into ovarian cancer. Altogether 189 patients were included in the study. Conventional cytogenetics as well as measurement of transcriptional activity of CTNNB1 (β-catenin) and HIF1A (HIF1-α) genes were prospectively studied in 60 endometriosis patients and 50 control group patients. The retrospective histopathological analysis was performed in 19 endometriosis associated ovarian cancer patients and 60 patients with histologically confirmed endometriosis. Results Five endometriosis patients showed a deviation from normal cytogenetics finding without affecting of their phenotype. In 6 cases of endometriosis associated ovarian cancer ectopic endometrium was not confirmed. The remaining 13 cases demonstrated either benign or atypical endometriosis or even structures of borderline carcinoma. Atypical endometriosis was histologically confirmed in 20% of 60 endometriosis patients. Determination of gene expression (CTNNB1, HIF1A) formed two subgroups. Transcriptionally incipient endometriosis subgroup with insignificant genes expression compared to control group. In transcriptionally evident endometriosis subgroup were genes expressions significantly higher compared to control group (p < 0.01) as well as transcriptionally incipient endometriosis subgroup (p < 0.05). Conclusions Significant structural abnormalities of chromosomes are not included in genetic rigging of endometriosis patients. Atypical endometriosis represents a histopathologically detectable intermediate of endometriosis progression. Determination of genes expression CTNNB1 and HIF1A helps to allocate risk patients with endometriosis where more precise management is needed.

Association between atypical endometriosis and ovarian malignancies in the real world

Background To evaluate the clinical outcome of atypical endometriosis and its association with ovarian malignancy. Methods This retrospective study included patients diagnosed with atypical endometriosis between January 2001 and December 2017. All patients had received surgical treatment for ovarian tumor. The clinical characteristics and histopathological results of all patients were reviewed. Results Atypical endometriosis was diagnosed in 101 patients. We analyzed 98 patients with a mean age of 34.8 years (range: 16–58 years). Ten patients (10.2%) had previously undergone endometriosis surgery more than once. In total, 12 (12.2%) patients had atypical endometriosis-associated ovarian malignancy—nine had carcinomas and three had borderline tumor. The tumors were pathologically classified as follows: five, clear cell carcinomas; two, endometrioid adenocarcinomas; one, mixed clear cell and endometrioid adenocarcinoma; one, seromucinous carcinoma; two, mucinous borderline tumors; and one, seromucinous borderline tumor. Conclusion Atypical endometriosis is most frequently associated with clear cell carcinoma and endometrioid adenocarcinoma. To identify the risk of ovarian malignancy and manage patients with endometriosis, diagnosing atypical endometriosis and recognizing its precancerous potential are important.

Clinical and Pathological Significance of Cellular Atypia in Endometriosis

Objective: To highlight the most frequent localization of ovarian endometriosis, the presence of atypical endometriosis, and recurrences. Retrospective review of 259 patients diagnosed with ovarian endometriosis treated at Tîrgu-Mures Emergency County Hospital, Obstetric Gynecology Clinic, between January 2014 and December 2018. Methods: Data were collected and analyzed for demographics, size of ovarian endometriotic cyst, and recurrences. Results: Out of 259 patients, 51 patients presented atypia, 20 on the right, 24 on the left, and seven patients were diagnosed with endometriosis with bilateral atypia. Higher susceptibility for left localization was noted. Thirty-nine patients (15.1%) presented recurrence. A statistically significant correlation (p = 0.006) was noted between patients with recurrence and atypia compared with those without atypia and endometriotic cysts larger than 7 cm. Patients with relapse under the age of 40 were noted to have mainly atypia with localization on the right (p = 0.025, OD = 4.107). Conclusion: The presence of endometrioma was not statistically significant correlated with left or right sided localization; recurrent endometriomas larger than 7 cm represents a risk for atypical endometriosis development. Recurrence and atypia appear more often in patients under the age of 40 and are right-sided. The total removal of the endometriomas can prevent the recurrence and subsequently the appearance of atypia and secondary neoplastic conditions.

Evaluation of PTEN and Ki67 Expression in Typical and Atypical Endometriosis and Endometriosis Associated Ovarian Cancer

Background: Several studies reported that endometriosis is associated with an increased risk of ovarian cancer. Atypical endometriosis is common in patients with endometriosis-associated ovarian, which might be considered as a precancerous lesion. Objectives: This study aimed to assess ki67 and PTEN expression in endometriosis associated ovarian cancer (EAOC), atypical endometriosis, and typical endometriosis. Methods: In this study, all H & E slides of 260 ovarian endometriosis cases were reviewed. And 25 cases were diagnosed with atypical endometriosis. Forty-one typical endometrioses and 24 ovarian cancers with endometriosis were included. We assessed PTEN and Ki67 immunoexpression in epithelial and stromal cells. Results: The prevalence of atypical endometriosis was about 9%. PTEN loss was found in 12 (out of 24 or 50%) of EAOC, 2 (out of 25; 8%) of atypical endometriosis, and none of the typical endometriosis. In all 12 PTEN loss cases, the PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. A total of 7.3% of typical endometriosis and 8% atypical endometriosis and 33.3% of EAOC had Ki67 staining in more than 50% of the epithelial component. Both typical and atypical endometriosis showed similar PTEN loss and Ki 67 staining (in more than 50% of the epithelial component) (P value > 0.05), and both of them were different from EAOC (P value < 0.05). Conclusions: The PTEN loss pattern in endometriosis adjacent to ovarian cancer was similar to that of ovarian cancer. The result indicated that PTEN loss could be an early event in the tumor development pathway from endometriosis to ovarian cancer.

Endometriosis-assEndometriosis-associated ovarian tumors: morphological and immunohistochemical features

Background. In 2016, the World Health Organization published an updated version of the Histological Classification for ovarian tumors presenting a new category of endometriosis-associated tumors. The predictors of malignant transformation of endometriosis have not been clearly defined so far.Purpose. The search for histological and immunohistochemical markers of endometriosis-associated malignancy.Materials and methods. 28 female patients with endometrioid ovarian cancer and 11 patients with clear cell ovarian carcinoma were enrolled. Histological and immunohistochemical studies were carried out using conventional techniques. Immunohistochemistry was applied to determine the hormone receptor status: expression of steroid hormone receptors, BAF250a (ARID1A), PTEN, P-catenin, MSH6, PMS2, р-53, WT-1, proliferative index (Ki-67). Microsatellite instability (MSI) testing was conducted according to the standard protocol.Results. In all cases of ovarian cancer, histological examination showed one of the endometriosis features. Atypical endometriosis was found in 39 % (11 / 28) of endometrioid tumors and in 9% (1/ 11) of clear cell carcinomas. Endometrioid ovarian cancer was found to be ER (74±7,8%) — and PR (67±5,4%) — positive; Ki-67 index was 68,2±3,7 %; loss of BAF250a (ARID1A) expression was observed in 14% (4/ 28), loss of PTEN expression in 29 % (8 / 28), nuclear expression of P-catenin in 32% (9/28) of cases. Loss of MMR expression was detected in 7% (2/28) of cases. MSI was found in one case only, which was also associated with loss of expression of BAF250a (ARID1A) and MSH6. Clear cell carcinoma of the ovary showed histological criteria for endometriosis; however, there were no changes immunohistochemical markers expression that were typical for endometriosis-associated malignancies. It could be due to a small number of patients in the group so further research is needed.Conclusion. Atypical endometriosis may be a morphological precursor of endometrioid and clear cell carcinoma of the ovary. Comprehensive assessment of a marker panel consisting of BAF250a (ARID1A), P-catenin, PTEN, p53, Ki-67 index, PMS2 and MSH6 will allow improving the diagnosis of atypical endometriosis and endometriosis-associated ovarian cancer.