Endometriosis: Is It Benign or Pre-Neoplastic? Analysis of Molecular Genetic Alterations in Ovarian Endometriosis
Wenbin Xiao, Amad Awadallah, Wei Xin. University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH
Background: A number of studies have demonstrated that endometriosis is a risk factor for ovarian clear cell and endometrioid carcinomas, and postulated that benign endometriosis may progress to atypical endometriosis, and eventually to ovarian clear cell and endometrioid carcinomas. Atypical endometriosis has been thought to be a pre-neoplastic lesion for these malignancies based on the fact that multiple molecular genetic alterations that are present in these cancers have also been identified in adjacent atypical endometriosis, such as mutations of ARID1A (encoding BAF250a, a recently identified tumor suppressor for these cancers), upregulation of hepatocyte nuclear factor (HNF)-1b, and loss of hormonal receptors expression, etc. A naturally arising but important question is whether benign endometriosis also harbors these molecular genetic alterations or not.
Design: Formalin-fixed paraffin-embedded blocks of ovarian resection specimens were selected. Endometriosis (N=36) was chosen as well as clear cell carcinoma (CCC, N=26). Atypical endometriosis was present in 13 out of 26 cases of CCC. Normal endometrium (N=5) was also included as a control. Immunohistochemical staining for BAF250a (ARID1A), HNF-1b, ER and PR was performed.
Results: CCC had loss of BAF250a expression (57.7%), HNF-1b upregulation (92.3%) and loss of ER and PR expression (92.3% and 85.6% respectively). Similar immunostaining profiles were present in atypical endometriosis and even in a small portion of benign endometriosis, but not in normal endometrium (table 1).
|BAF250a N(%)||HNF-1b N(%)||ER N(%)||PR N(%)|
|Normal endometrium (N=5)||5(100%)||0(0)||5(100%)||5(100%)|
|Benign endometriosis (N=36)||28 (77.8%)**||12 (33.3%)**||28 (77.8%)**||18 (50%)**|
|Atypical endometriosis (N=13)||5 (38.5%)*||7 (53.8%)||2 (15.4%)*||3 (23.1%)|
|CCC (N=26)||11 (42.3%)*||24 (92.3%)*||2 (7.7%)*||4 (15.4%)*|