Role of endometriosis as a prognostic factor for post‑progression survival in ovarian clear cell carcinoma

Abstract

Abstract.The clinical significance of coexistence of endometriosis (EM) in ovarian clear cell carcinoma (CCC) has not yet been determined. The aim of the present study was to analyze the correlation of endometriosis with clinicopathological factors in CCC. The cases with CCC that received primary debulking surgery at the present hospital between 1990 and 2013 were identified. Retrospective analysis was conducted to evaluate the association between complications with EM and clinicopathological features in CCC. Of the 105 cases enrolled in the study, 45 cases were complicated with EM, and 60 cases did not have EM (non-EM). The patients with EM were diagnosed at a younger age (P=0.03), and at earlier stages (P<0.01) compared with non-EM cases. Although there was no significant difference of progression-free survival (P= 0.36), complications with EM were identified as an independent prognostic factor for overall survival (OS; P<0.01) by multivariate analysis. A total of 48 patients (45.7%) developed recurrence: 18 patients in EM-group and 30 patients in non-EM group. There were no significant differences of clinicopathological factors in the treatment at recurrence between both groups. Recurrent cases in EM had significantly worse post-progression survival (PPS) compared with recurrent non-EM group (P<0.01). Multivariate analysis for PPS demonstrated that complications with EM (P<0.01) were identified as a worse prognostic factor. In CCC, the complication with EM was identified as a significant worse prognostic factor for PPS in recurrent cases. Additionally, EM was significantly associated with OS in all cases with CCC. Novel treatment strategies are therefore necessary for recurrent CCC, particularly for cases exhibiting EM.

The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells

“…Moreover, the mechanism of action underlying the effect of SMYD2 on cell proliferation and apoptosis, including the potential role of p53 methylation, has not been addressed. Lastly, endometriosis is reportedly a precursor of OCCC (34), and therefore analysis of SMYD2 expression in OCCC should be compared with normal ovarian tissues as well as with tissues of endometriosis in the future. Nevertheless, the present findings suggest that SMYD2 increases the proliferation of OCCC cells in vitro, suggesting a potential therapeutic avenue for SMYD2 inhibition in the treatment of OCCC.…”

Clear cell carcinoma of the ovary

“…Although some studies concluded that presence of endometriosis was not a prognostic factor, [15,33,34] others reported that endometriosis was an independent predictor of better survival [35] or worse survival. [36] However, one should note that many studies comparing survival of OCCC with or without endometriosis did not draw a clear distinction between cancer with coexisting endometriosis and cancer arising from endometriosis. As these may be 2 different subgroups of OCCC, the results of these studies should be interpreted cautiously.…”

Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma

“…The association of endometriosis and ovarian cancer has been widely reported 43 , 44 . Between 18% and 43% of women with OCCC have a history of endometriosis 19 , 45 - 48 , and several studies have demonstrated that this benign disease is a precursor lesion of OCCC and endometrioid carcinoma 21 .…”

“…Moreover, endometriosis was found to be associated with amplification of epidermal growth factor receptor (EGFR) gene and the activation of EGFR plays a critical role in cell proliferation, apoptosis, angiogenesis, and metastasis 16 , thus it is necessary to identify whether the amplification of EGFR can trigger the progression from endometriosis to carcinoma. The risk of tumorigenesis in endometriosis is about 1% among premenopausal women and 1% to 2.5% among postmenopausal women 45 , 53 . The risk for 20-year-old women is considered to be 1.00, therefore the risks for women in their 40s and 50s are 3.60 and 10.7, respectively, which indicates that the tumorigenesis of endometrial cysts occurred around menopause 54 .…”

“…Patients with pathologically confirmed endometriosis-associated OCCC are 4 to 8 years younger at diagnosis than those without endometriosis 53 , 213 , 214 , and they are more likely to diagnosed at early-stage manifestations and have higher probability of optimal debulking, lower CA-125 levels, and a higher rate of platinum-sensitivity 19 , 45 , 46 , 48 . Patients with endometriosis-associated OCCC also tend to have lower percentages of LNM (15% to 17% vs 40% to 41%) and lymphovascular space invasion (LVSI) (23% vs 51%) compared with those without endometriosis-associated OCCC 46 , 72 .…”