| ObjectiveThough endometriosis is one of the most common benign gynecological disease, it has now been discovered to have the ability for malignant transformation and sharing a close relationship with ovarian clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC). The concept of "endometriosis associated ovarian cancer" (EAOC) was then presented to describe the subgroup disease which shown a specific characteristic of tumor origin, development and clinical-prognostic manifestation when comparing with other ovarian epithelial cancers. In our study, we retrospectively reviewed the clinical and prognostic information of CCC and EAC patients with or without endometriosis, aiming to discover the characteristics of patients with EAOC.MethodsWe retrospectively collected a total of 309 cases who were diagnosed with CCC or EAC and received primarily treatment at the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital. By reviewing the medical database of those patients, we analyzed the clinical characters of patients with or without endometriosis including pre-operative information, surgical and pathological results. We also performed prognostic analysis by using Kaplan Meier survival curve and Cox regression model to discover the risk factors related to CCC and EAC.ResultEAOC group patients were proved to be younger, more likely to be pre-menopausal, more likely to have lower preoperative serum CA125 level, with earlier stage and more likely to receive optimal debulking surgery and sharing a lower mortality and relapse rate when compared to non-EAOC patients. The univariate analysis showed that age, menopause status, stage, tumor residual and concurrent of endometriosis were significant prognostic factor for OS and DFS. Multivariate analysis showed menopause and stage were independent risk factors for OS while stage and tumor residual were independent risk factors for DFS.ConclusionEAOC patients show a specific clinical features and always have a better outcome when comparing with non-EAOC. Endometriosis itself is not an independent prognostic factor for CCC and EAC.ObjectiveEndometriosis associated ovarian cancer always has a different clinical and prognostic character compared with endometriosis not associated cancers, which may indicates that they share distinct tissue origin and transformation pathway. A serious of researches have been conducted to demonstrate that the malignant transformation of endometriosis is the result of a complex mechanisms including oxidative stress, inflammatory factors and estrogen choosing, while some molecular change may also play a critical role in this process. This study was designed by using whole exome sequencing to identify the probable molecular mechanism of endometriosis transformation.MethodWe reviewed the clinical and pathological diagnosis of patients with endometriosis transformation to ovarian endometrioid adenocarcinoma by Sampson and Scott’s criteria. Then we conducted laser captured microdissection to obtain exact tissues of benign ovarian endometriosis, atypical endometriosis and endometrioid carcinoma. By using whole exome sequencing analysis, we compared those variable mutations among different tissues and identify the probable molecular mechanism of endometriosis transformation.ResultThe whole exome sequencing on benign endometriosis, atypical endometriosis and endometrioid carcinoma showed 57911,18768 and 69001 exon mutations in each one. By filtration of non-functional mutation and comparing with genomic database, we identified 21 same exon mutations between aEM and EAC tissues. Among those mutations, the gene CDKN2AIP, UIMC1 and TPBG acted as an important part in choice of cell proliferation or apoptosis fate, DNA damage repair system and regulation of Wnt signaling pathway.ConclusionCDKN2AIP, UIMC1 and TPBG may play critical role in the transformation from ovarian endometriosis to endometrioid carcinoma.
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