The immunohistochemical molecular risk classification in endometrial cancer: A pragmatic and high-reproducibility method.

INTRODUCTION: The aim of this study is to assess the clinical reproducibility and the potential oncological validity of the molecular information provided by the immunohistochemistry (IHC) to properly stratify the endometrial cancer patients. METHODS: Retrospective IHC analyses were conducted in a large series of 778 pre-operative uterine-confined ECs, studying the presence/absence of MLH1, MSH2, MSH6 and PMS2 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 data. RESULTS: Based on IHC assessment, we defined 3 EC populations: stable MMR patients (MMRs), instable patients (MMRi) and p53 mutated patients (p53+). Our result demonstrated that the IHC stratification statistically correlated with the most relevant pathologic-clinical features: FIGO stage (p < 0.001), grading (p < 0.001), histotype (p < 0.001), presence of LVSI (p < 0.001), myometrial invasion and tumor dimension (p = 0.003 for both). These 3 IHC populations statistically reflected the EC risk class ESGO-ESMO-ESP classification 2021 (p < 0.001). These results were also confirmed in the Kaplan-Meier curves in terms of overall survival (OS) and disease-free survival (DFS) (p < 0.0001). 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 the DFS (p = 0.041 and p = 0.004). CONCLUSION: In this large series, we demonstrated that the pragmatic and systematic use of IHC may have an important role to properly stratify, in terms of histological features and clinical outcomes, the EC patients.

Semiquantitative evaluation of lymph-vascular space invasion in patients affected by endometrial cancer: Prognostic and clinical implications.

OBJECTIVES: The interpretation of lymph-vascular space invasion (LVSI) is usually qualitative, as presence or absence. The aim of this study is to investigate the prognostic role of LVSI in patients affected by endometrial cancer, when evaluated with a semiquantitative analysis. METHODS: This retrospective multicentre study enrolled patients who received a histologically confirmed diagnosis of endometrial cancer. The assessment of LVSI was semiquantitative in accordance with the three-tiered scoring system (absent, focal and diffuse). RESULTS: Among 1258 patients with surgical-stage endometrial cancer, LVSI has been found in 32.8% of cases (n = 412), whose 12.7% (n = 160) were focal, and 20% (n = 252) diffuse. The rate of lymph node metastasis increased from the 5% in patients with no LVSI to 15% in patients with focal LVSI and 33% in those with diffuse LVSI (p < 0.001). Distant recurrences were more frequent in patients with diffuse LVSI than in focal or no LVSI (24.9% versus 14.7% and 6.6%, respectively, p < 0.001). Diffuse LVSI was found to significantly increase the risk of distant metastasis (adjusted odds ratio (A OR) 2.57, p < 0.001). Adjuvant radiation were associated with improved overall survival (OS) and disease-free survival (DFS) in patients with diffuse LVSI. CONCLUSION: The presence of diffuse LVSI is an independent risk factor for both lymph node metastasis and distant recurrence in endometrial cancer patients, and it is associated with a significantly decreased OS and DFS. Adjuvant radiation improved survival regardless of grading, histotype and lymph nodal metastasis in women with diffuse LVSI.