Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Gynecol Oncol. 2022 Sep;166(3):530-537. doi: 10.1016/j.ygyno.2022.06.027. Epub 2022 Jul 13.
Microcystic, elongated fragmented (MELF) pattern of myometrial invasion is a distinct histologic feature occasionally seen in low-grade endometrial carcinomas (EC). The prognostic relevance of MELF invasion was uncertain due to conflicting data, and it had not yet appropriately been studied in the context of the molecular EC classification. We aimed to determine the relation of MELF invasion with clinicopathological and molecular characteristics, and define its prognostic relevance in early-stage low/intermediate risk EC.
Single whole tumor slides of 979 (85.8%) out of 1141 (high)intermediate-risk EC of women who participated in the PORTEC-1/-2 trials were available for review. Clinicopathological and molecular features were compared between MELF invasion positive and negative cases. Time-to-event analyses were done by Kaplan-Meier method, log-rank tests and Cox' proportional hazards models.
MELF invasion was found in 128 (13.1%) cases, and associated with grade 1-2 histology, deep myometrial invasion and substantial lymph-vascular space invasion (LVSI). 85.6% of MELF invasion positive tumors were no-specific-molecular-profile (NSMP) EC. NSMP EC with MELF invasion were CTNNB1 wild type in 92.2% and KRAS mutated in 24.4% of cases. Risk of recurrence was lower for MELF invasion positive as compared to MELF invasion negative cases (4.9% vs. 12.7%, p = 0.026). However, MELF invasion had no independent impact on risk of recurrence (HR 0.65, p = 0.30) after correction for clinicopathological and molecular factors.
MELF invasion has no independent impact on risk of recurrence in early-stage EC, and is frequently observed in low-grade NSMP tumors. Routine assessment of MELF invasion has no clinical implications and is not recommended.
微囊性、拉长性碎片（MELF）的子宫肌层浸润模式是低级别子宫内膜癌（EC）中偶尔出现的一种明显的组织学特征。由于数据相互矛盾，MELF 浸润的预后相关性尚不确定，并且在 EC 的分子分类背景下尚未得到适当研究。我们旨在确定 MELF 浸润与临床病理和分子特征的关系，并定义其在早期低/中危 EC 中的预后相关性。
参与 PORTEC-1/-2 试验的 1141 例（高危）中危 EC 患者的 979 例（85.8%）肿瘤的全肿瘤切片可用于回顾性分析。比较 MELF 浸润阳性和阴性病例的临床病理和分子特征。采用 Kaplan-Meier 法、对数秩检验和 Cox 比例风险模型进行生存时间分析。
发现 128 例（13.1%）病例存在 MELF 浸润，与组织学 1-2 级、深层子宫肌层浸润和大量淋巴血管间隙浸润（LVSI）相关。85.6%的 MELF 浸润阳性肿瘤为无特异性分子谱（NSMP）EC。MELF 浸润阳性的 NSMP EC 中 CTNNB1 野生型占 92.2%，KRAS 突变型占 24.4%。与 MELF 浸润阴性病例相比，MELF 浸润阳性病例的复发风险较低（4.9%比 12.7%，p=0.026）。然而，在纠正临床病理和分子因素后，MELF 浸润对复发风险无独立影响（HR 0.65，p=0.30）。
MELF 浸润对早期 EC 的复发风险无独立影响，并且在低级别 NSMP 肿瘤中经常观察到。常规评估 MELF 浸润没有临床意义，不推荐使用。
