GENERAL INTRODUCTION 13 1 are considered the most important explanations for this disagreement.17, 20-23 Besides, it remains unclear whether the amount of diagnostic tissue impacts the concordance. Immunohistochemical biomarkers In recent years, several IHC biomarkers have been studied in EC to improve diagnosis and prognostication of which ER, progesterone receptor (PR), p53 and L1 cell adhesion molecule (L1CAM) appear the most relevant. Examples of expression patterns of these biomarkers are shown in Figure 2.30-37 Positive ER/PR expression is associated with favorable outcome and low risk of lymph node metastasis (LNM). Negative ER/PR expression is associated with the opposite.37, 38 Our research group recently demonstrated that a revised three-tiered ER and PR risk classification improves prognostication over the commonly used cutoff value of 10% for ER and/or PR positivity: 0-10% with most unfavorable outcome, 20-80% with intermediate outcome and 90-100% with most favorable outcome.39 TP53 is the most frequently mutated gene, causing dysfunction of p53 tumor suppressor protein, playing an important role in cell proliferation, apoptosis, DNA repair and genomic stability. Overexpression of p53 or null-expression is associated with an unfavorable outcome. 40-42 The transmembrane L1CAM is critical for epithelial to mesenchymal transition (EMT) and cancer initiating cell (CIC) formation which may result in chemotherapy resistance.32, 43 Positive L1CAM tumor expression is associated with a poor outcome in EC.32, 44-47 Currently, most of these easy accessible IHC biomarkers are not yet used in the risk classifications for primary and secondary treatment.
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