Department of Gynecologic Oncology Surgery, Istituto Nazionale Tumori, IRCSS, "Fondazione G. Pascale", Naples, Italy.
Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori, IRCSS, "Fondazione G. Pascale", Naples, Italy.
Eur J Obstet Gynecol Reprod Biol. 2019 Sep;240:220-225. doi: 10.1016/j.ejogrb.2019.07.013. Epub 2019 Jul 13.
To test the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and determine the frequency of specific/prognostic molecular alterations within a cohort of endometrial cancer (EC) women conservatively treated by combined hysteroscopic resection and progestin therapy.
We used blocks of formalin-fixed paraffin-embedded tissue from the primary tumors of patients enrolled into the ECCo trial (EudraCT 2010-018581-23) between 2007 and 2016. In order to assign EC resectoscopic specimens to one of four ProMisE subgroups, testing involved sequential assessment of i) immunohistochemistry (IHC) for mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2; ii) sequencing for POLE/POLD1 exonuclease domain mutations (EDMs); iii) p53 IHC.
Molecular analysis methods were used in 25 patients (stage IA, G1-2 endometrioid EC), of whom 15 (60%) represented fully evaluable cases. Seven cases (46.7%) had abnormal MMR IHC, POLE/POLD1 EDMs were found in 3 cases (20%), and abnormal p53 IHC in 1 case (6.6%). Three patients (20%) had more than one molecular feature. Among 10 (40%) 'unclassifiable' patients, six failures in achieving complete molecular categorization were due to the low tumor volume. Molecular classification of the 15 fully evaluable cases yielded the following ProMisE subtypes: 7 (46.7%) MMR IHC abnormal, 1 (6.6%) POLE EDM, 0 (0%) p53 IHC abnormal, 7 (46.7%) p53 IHC wild-type.
Although larger series are needed to further assess the feasibility of a molecular categorization in a fertility-sparing setting, data presented are promising. In women with early stage low-volume disease, operative hysteroscopy could be advantageous to provide samples allowing complete genetic risk assessment.
测试子宫内膜癌主动式分子风险分类器（ProMisE），并确定在一组接受联合宫腔镜切除术和孕激素治疗的保守治疗的子宫内膜癌（EC）女性中特定/预后分子改变的频率。
我们使用了 2007 年至 2016 年期间纳入 ECCo 试验（EudraCT 2010-018581-23）的患者的原发性肿瘤的福尔马林固定石蜡包埋组织块。为了将 EC 经阴道切除术标本分配到 ProMisE 四个亚组之一，检测包括以下步骤的连续评估：i）免疫组织化学（IHC）用于错配修复（MMR）蛋白 MLH1、MSH2、MSH6 和 PMS2 的检测；ii）POLE/POLD1 外切酶结构域突变（EDMs）的测序；iii）p53 IHC。
分子分析方法用于 25 例患者（IA 期，G1-2 子宫内膜样 EC），其中 15 例（60%）为完全可评估病例。7 例（46.7%）存在异常 MMR IHC，3 例（20%）发现 POLE/POLD1 EDMs，1 例（6.6%）存在异常 p53 IHC。3 例（20%）有超过一种分子特征。在 10 例（40%）“无法分类”的患者中，有 6 例由于肿瘤体积小而导致分子分类完全失败。对 15 例完全可评估病例的分子分类得到以下 ProMisE 亚型：7 例（46.7%）MMR IHC 异常，1 例（6.6%）POLE EDM，0 例（0%）p53 IHC 异常，7 例（46.7%）p53 IHC 野生型。
尽管需要更大的系列来进一步评估在保留生育力的环境中进行分子分类的可行性，但目前的数据是有希望的。对于早期低体积疾病的女性，手术性宫腔镜检查可能具有优势，因为它可以提供样本，从而进行完整的遗传风险评估。
