PTEN公司
孕激素
张力素
生物标志物
活检
免疫组织化学
肿瘤科
病理
医学
内科学
生物
雌激素
生物化学
PI3K/AKT/mTOR通路
细胞凋亡
作者
Hao Chen,Elena Lucas,Amanda Strickland,Kelley Carrick,Katja Gwin,Diego H. Castrillón,Glorimar Rivera-Colón,Shuang Niu,Kyle Molberg,Wenxin Zheng
标识
DOI:10.1097/pas.0000000000001537
摘要
Background: Conservative management with progestin is a treatment option for atypical hyperplasia (AH). However, pathologic diagnosis of residual/recurrent lesions is often problematic because of the profound morphologic changes induced by progestin and the lack of established diagnostic criteria for progestin-treated residual AH. Methods: We conducted a longitudinal study of 265 endometrial biopsies from 54 patients with a history of AH on progestin therapy. Patient outcomes were divided into 3 categories after morphologic review and immunohistochemical staining with phosphatase and tensin homolog (PTEN) and paired box 2 (PAX2): (1) persistent or residual disease; (2) recurrent disease; (3) complete response. All specimens were classified into 3 categories based on morphology: (1) persistent/recurrent disease (nonresponse), (2) morphologically uncertain response, (3) optimally treated (complete response). The staining patterns of PTEN/PAX2 were tracked over time in individual patients and correlated with morphologic findings before and after progestin therapy. Results: Our data showed that aberrant expression patterns of PTEN and/or PAX2 were identified in 48 (88.9%) of the 54 primary biopsies and persisted in persistent/recurrent AH across serial endometrial biopsies (n=99, P <0.00001), while normal PTEN and PAX2 expressions were consistently observed in optimally treated cases (n=84, P <0.00001). More importantly, follow-up biopsies that showed a morphologically uncertain response but a PTEN/PAX2 expression pattern identical to the initial biopsy were significantly correlated with persistent or recurrent disease (n=18, P =0.000182), as evidenced by areas with morphologic features diagnostic of AH on subsequent biopsy. Conclusions: Biomarker PTEN/PAX2 signatures offer a valuable diagnostic aid to identify residual AH in progestin-treated endometrial samples for which the biomarker status from preprogestin treated AH is known. The findings of this study are promising for a possible future change of diagnostic practice.
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