Molecular classification of endometrial carcinoma: protocol for a cohort study (Preprint)

UNSTRUCTURED Endometrial carcinoma (EC) is the most common gynaecologic malignancy in developed countries and the fourth most frequent in women worldwide. Incidence of EC has been increasing in the past several years, mainly due to increasing rates of metabolic syndrome. The cornerstone of treatment for EC is surgery. Clinicopathological features are currently used to help determine the individual risk of recurrence and the need for adjuvant treatment after surgery. Nonetheless, there is a significant inter-observer variability in assigning histologic subtype when using a morphological classification, revealing the need for a more unified approach. The Cancer Genome Atlas (TCGA) project identified four distinct prognostic EC subtypes based on genomic abnormalities. Surrogate assays including three immunohistochemical markers (p53, MSH6 and PMS2) and one molecular test (mutation analysis of the exonuclease domain of POLE), allowed the development and validation of a simplified molecular classifier that correlates with the TCGA classification, has prognostic value and can easily be used in clinical practice. This molecular classification categorizes EC in 4 subtypes: POLE mutated, mismatch repair deficient, p53 abnormal and no specific molecular profile. Applying this classification in clinical practice will help tailor adjuvant treatment decisions. The aim of this study is to retrospectively apply this novel molecular classification on a cohort of EC patients treated in a comprehensive cancer centre, to assess its applicability in clinical practice, to evaluate clinical outcomes by molecular subtypes and assess its prognostic value.