Introduction/Background*Nowadays, after the recent insights about the molecular Endometrial cancer (EC) classification, the usual key histological parameters (i.e histotype and grade) have been shown to have poor reproducibility and adequacy in EC stratification risk. The need to define a more precise guidance of surgical and adjuvant approaches has suggested the possibility to refine the prognostic assessing, considering other EC characteristics. Inspired by these concepts, the aim of this study is to assess the clinical reproducibility and the oncological validity of the EC risk stratification based on the molecular information given by the immunohistochemistry (IHC).

Methodology Retrospective IHC analyses were conducted in a large series of 778 pre-operative uterine-confined ECs, studying the presence/absence of MLH1, MSH2, MSH6, to define the mismatch repair (MMR) stable or instable phenotype; the presence of p53 mutations and other molecular features. The molecular profile was correlated with histological, clinical and prognostic EC patients data.

Result(s)*Based on the IHC, we defined 3 EC populations: MMR stable (MMRs), instable (MMRi) and p53 mutated (p53+) patients. Our result demonstrated that the IHC stratification statistically correlated with the most relevant anatomo-clinical features: FIGO stage (p<0.001), grading (12,5% G3 in MMRs vs 22.9% in MMRi vs 95.3% in p53+, p<0.001), histotype (Type II 6.2% in MMRs vs 5.3% in MMRi vs 87.5% in p53+, p<0.001), presence of LVSI (positive in 16.3% in MMRs vs 23.8% in MMRi vs 38.7% in p53+, p<0.001), myometrial invasion and tumor dimension (p=0.003 and p<0.001 respectively). Again, the 3 IHC populations statistically reflected the EC risk class ESGO-ESMO-ESP classification 2020 (p<0.001) (table 1). These results were confirmed also in Kaplan-Meier curves in terms of over-all survival (OS) and disease-free survival (DFS) (p<0.0001) (figure 1). Moreover, the multivariate analyses demonstrated that absence of estrogen receptor (ER) impacted the OS (p=0.011) and, the Age>60 years and the ER-status in DFS (p=0.004 and p=0.041).

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Abstract 86 Figure 1

Conclusion*In this large series, we demonstrated that the pragmatic and sistematic use of IHC may have an important role to properly stratify, in terms of histological features and clinical outcome, the pre-operative uterine-confined EC patients.