Clinicopathologic association and prognostic impact of microcystic, elongated and fragmented pattern invasion, combined with tumor budding in endometrioid endometrial cancer.

ABSTRACT

AIM: As a special invasive pattern seen in low-grade endometrial carcinoma, microcystic, elongated and fragmented (MELF) pattern is related to lymph node metastasis. Tumor budding (TB) is another histological marker in many cancers associated with tumor aggressiveness. Herein, we evaluated the impact of MELF pattern combined with TB about clinicopathological features and prognosis in endometrioid endometrial cancer (EEC). To verify the relationship between the two morphological markers and microsatellite status in EEC, the primary mismatch repair (MMR) proteins were detected by immunohistochemistry. METHODS: One hundred and seventy-two cases of ECC diagnosed between 2011 and 2016 were reviewed with a median follow up of 47.5 months. MELF pattern and TB were examined on all H&E-stained slides. Primary MMR proteins (MLH1, MSH2, MSH6, and PMS2) were also detected. RESULTS: Based on MELF pattern and TB, 172 patients were divided into the following four groups MELF(-)/TB(+) (n = 41), MELF(+)/TB(-) (n = 15), MELF(+)/TB(+) (n = 20), and MELF(-)/TB(-) (n = 96). Adverse pathological features were observed in the MELF(+)/TB(+) group 70% presented deep muscular infiltration, 65% were lymphovascular space invasion, and 25% suffered lymph node metastasis. The proportion of MMR deficient in MELF(+)/TB(-) group was the highest (66.7%). The progression-free survival (PFS) and overall survival (OS) among the four groups were significantly different. MELF(+)/TB(+) group showed the worst PFS and OS. As univariate and multivariate survival analyses revealed, the combination of MELF pattern and TB was confirmed as an independent predictor of poor prognosis. CONCLUSIONS: Our research demonstrates that MELF pattern combined with TB, as an independent predictor of adverse outcome, is associated with adverse pathological features, which facilitates better understanding of EEC tumor behavior and more precise prognosis without additional medical expense.