223 Endometrial carcinoma molecular subtype correlates with the presence of lymph node metastases

Abstract

<h3>Introduction/Background*</h3> The role of lymph node (LN) assessment in endometrial cancer (EC) has been a subject of debate for decades, with significant variation in use between centres. Molecular classification of EC provides objective, prognostic information and be performed on diagnostic endometrial biopsy specimens. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) uses targeted next-generation sequencing to detect pathogenic <i>POLE</i> exonuclease domain mutations (<i>POLEmut</i>) and immunohistochemistry to evaluate for the presence of mismatch repair deficiency (MMRd), <i>TP53</i> mutations (p53abn) or tumours with no specific molecular profile (NSMP/p53wt). Herein, we assessed the association between EC molecular subtype and LN metastases in a single institutional cohort with a uniform approach to LN assessment. <h3>Methodology</h3> All ECs treated with primary surgery from a single institution in 2015 underwent ProMisE molecular subtyping and collection of clinicopathologic and outcomes data. <h3>Result(s)*</h3> Complete pelvic and para-aortic lymphadenectomies were performed in 171 of 172 consecutive cases of EC. The distribution of ProMisE subtypes and clinicopathologic features associated with molecular subtype are outlined in table 1. The p53abn subtype was observed across a range of EC histotypes, including low grade endometrioid endometrial carcinoma. LN metastases were found in 31/171 (18.1%) patients: pelvic only in 83.9% and pelvic plus para-aortic in 16.1%. LN metastases included macrometastases (19/31), micrometastases (5/31), and isolated tumour cells (ITCs) (7/31). Molecular subtype was significantly associated with LN metastases (<i>p=0.004</i>); there was a strong association between LN metastases and p53abn EC (nodal involvement in 44.8% of cases). LN metastases were observed in 14.2% of<i> POLE</i>mut, 14.9% of MMRd, and 10.8% of NSMP EC. By multivariate analysis, molecular subtype and CA 125 &gt;25 kU/L were significantly associated with LN metastases (<i>p</i>=0.021 and <i>p</i>=0.022 respectively) compared to histotype, which showed no significant association with LN status (<i>p</i>=0.24). <h3>Conclusion*</h3> EC molecular subtype significantly associates with LN metastases and offers objective, reproducible, and prognostic information from diagnostic specimens. Pre-operative knowledge of molecular subtype can guide biologically-informed approaches to LN sampling, particularly for patients with high molecular risk (p53abn) EC.