Molecular Subgroups of Endometrial Carcinoma in Romanian Patients

Abstract

Molecular classification of endometrial carcinoma (EC) has represented a breakthrough ever since the TCGA (The Cancer Genome Atlas) project published it in 2013. Four distinct molecular subgroups were recognized based on somatic copy number alterations and tumor mutational burden: POLE (polymerase-epsilon) ultramutated, MSI (microsatellite instability) hypermutated (MSI-H), copy number low (CNL) and copy number high (CNH). However, implementing a standardized algorithm in current practice is far from being definitive. Our purpose in this study was to determine different molecular subgroups in a cohort of Romanian patients using cost effective and available immuno-histochemistry markers and outline statistical associations with different parameters. Tissue microarrays encompassing 50 cases with previously diagnosed ECs were tested for ER, PR, HER2, p53, MSH6 and PMS2 and results showed 68% MSI-H cases with statistical correlation with tumor size ] 2 cm (p=0.028) and no association with overall survival. CNH ECs were reported in 26% of cases and showed important statistical significance with TILs (p=0.041) and no correlations with overall survival. The CNL subgroup was reported in 74% of ECs cases and showed statistical significance with the histopathological subtype (p=0.006), pT (removal of primary tumor according to AJCC/UICC convention) (p=0.033), risk category according to ESMO (European Society of Medical Oncology) criteria (p=0.022) and ER expression (p=0.002). Five-year overall survival was 84%. Molecular classification is an important additional tool in current pathology guidelines for reporting ECs, but it is not currently standardized or available in all laboratories. Its importance in evolving treatment strategies for this disease is well documented so we strongly recommend routine testing for molecular prognostic factors.

Tumour microenvironment and PD-L1 expression in endometrial carcinoma

“…It has also been documented that increased TME induces PD-1/PD-L1 mediated fluctuating immune resistance, which usually leads to aggressive tumour phenotype and a poor prognosis. In our study, PD-L1 expression was highly correlated with this subgroup that additionally showed other unfavourable prognostic parameters: younger age, higher FIGO grade, deep myometrial invasion, tumour size, and positive LVSI 7 . Similar results were found in other studies 21 .…”

“…The samples of endometrial carcinomas were reviewed, cored (1 mm) in triplicate and arrayed as previously described 7 . Tissue microarray (TMA) sections were stained with antibodies against CD4 (Ventana, catalogue number 790-4423, clone SP35, Rabbit), CD8 (Ventana, catalogue number 790-4460, clone SP57, Rabbit), CD68 (Ventana, catalogue number 790-2931, clone KP-1, Mouse) and PD-L1 (Ventana, catalogue number 790-4907, clone SP263, Rabbit).…”

Βeta-catenin – an important immunohistochemical tool in stratifying endometrial carcinomas?

“…The cases selection was performed from a previous database 7 and included 50 cases of ECs from the Pathology Department archives, diagnosed between 2014 and 2019. Molecular classification for ECs was already performed and divided the cohort into four subgroups: MSS subgroup, MSI subgroup, p53abn subgroup and p53wt subgroup 7 . In addition, Programmed Death -Ligand 1 (PD-L1) testing was assessed on this cohort 8 .…”

“…The obtained samples of endometrial carcinoma were reviewed, cored (1mm) in triplicate and arrayed as previously described 7 . Tissue sections were stained with antibodies against -catenin (Ventana, catalogue number 760-4242, clone 14, Mouse) and protocol was followed for staining.…”