Departments of Pathology.
Obstetrics and Gynecology.
Am J Surg Pathol. 2020 Oct;44(10):1429-1439. doi: 10.1097/PAS.0000000000001537.
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.
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.
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.
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.
孕激素保守治疗是不典型增生（AH）的一种治疗选择。然而，由于孕激素引起的形态学变化很大，以及缺乏针对孕激素治疗后残留 AH 的既定诊断标准，对残留/复发病灶的病理诊断通常存在问题。
我们对 54 例接受孕激素治疗的 AH 病史患者的 265 份子宫内膜活检进行了纵向研究。在进行形态学复查和磷酸酶张力蛋白同源物（PTEN）及配对盒 2（PAX2）免疫组织化学染色后，将患者的结果分为 3 类：（1）持续存在或残留疾病；（2）复发性疾病；（3）完全缓解。所有标本均基于形态学分为 3 类：（1）持续/复发病变（无反应），（2）形态学不确定反应，（3）最佳治疗（完全缓解）。在个体患者中跟踪了 PTEN/PAX2 的染色模式，并与孕激素治疗前后的形态学发现相关。
我们的数据显示，在 54 例原发性活检中，48 例（88.9%）存在 PTEN 和/或 PAX2 的异常表达模式，并且在连续的子宫内膜活检中（n=99，P<0.00001），这些异常表达模式在持续性/复发性 AH 中持续存在，而在最佳治疗的病例中（n=84，P<0.00001）始终观察到正常的 PTEN 和 PAX2 表达。更重要的是，表现出形态学不确定反应但 PTEN/PAX2 表达模式与初始活检相同的后续活检与持续性或复发性疾病显著相关（n=18，P=0.000182），因为随后的活检中存在 AH 的形态学特征诊断区域。
生物标志物 PTEN/PAX2 特征可作为一种有价值的诊断辅助手段，用于识别孕激素治疗后子宫内膜样本中的残留 AH，其中已知孕激素治疗前 AH 的生物标志物状态。本研究的结果为未来改变诊断实践提供了希望。
