CHAPTER 8 184 This new grading system considers both grade 1 and 2 EC lumped together as low-grade EC and grade 3 endometrioid EC (EEC) and non-endometrioid EC (NEEC) as high-grade EC.9, 10 We confirmed that, by using this binary classification, the concordance between pre- and postoperative diagnosis resulted in an improved percentage of 88.8%. However, this binary classification inherently covers the poor interobserver reproducibility specifically for grade 2 EC. This may still impact treatment decisions when the correct diagnosis is either low- or high-grade EC. The standard use of a simple and relatively cheap set of IHC markers is therefore recommendable.4, 11-15 This set includes the most studied IHC markers over the years: estrogen receptor (ER), progesterone receptor (PR), L1 cell adhesion molecule (L1CAM) and p53. ER/PR are well-known prognostic hormonal biomarkers that predict LNM and outcome in EC.16, 17 Additionally, positive L1CAM expression is also an established prognosticator for LNM and outcome in EC.18-23 Finally, p53 is one of the most well-known IHC markers for several tumors; abnormal expression of p53 (overexpression or null-expression) is associated with an unfavorable outcome, representing 15% of all EC diagnosis and responsible for 5070% of all EC-related mortality.24-30 Furthermore, it is associated with NEEC histology and LNM.20-22, 31 In our clinical oncology network, routine evaluation of PR and p53 is now recommended in preoperative grade 2 EC. Preliminary results of ongoing research shows, that patients with preoperative grade 2 EC, p53 abnormal and/or PR negative expression, have a worse prognosis comparable to high-grade EC. Underlining the fact that patients with doubtful lowgrade EC, such as grade 2 EC might benefit from routine IHC to improve binary grading into low and high, and is expected to improve reproducibility.9, 30, 32, 33 Preoperative risk stratification Primary treatment of EC consists of hysterectomy with bilateral salpingo-oophorectomy with or without lymph node assessment. Approximately 10% of all patients have lymph node metastases (LNM), which can be predicted and/or diagnosed by an algorithm directing approach for staging, integrated risk classification, routinely sentinel lymph node (SLN) mapping or full lymph node dissection (LND).9, 34, 35 According to the most recent ESGO/ ESTRO/ESP guideline, surgical treatment is based on determining preoperative tumor grade and histology by endometrial biopsy. In addition to grade, deep myometrial invasion (MI) is an important pathological finding that is associated with increased risk of LNM.34 Preoperatively, MI may be detected with TVU or MRI.9, 36 Reported sensitivity and specificity of TVE for deep MI are 71-85% and 72-90%, respectively. For contrast enhanced MRI, the sensitivity and specificity for deep MI are 33-100% and 44-100%, respectively. Depending on clinical and pathological risk factors, imaging for detection of metastatic disease is considered.9 LN surgery is particularly recommended in high-grade EC, and may be considered in low-grade EC. Routine lymphadenectomy in low-grade EC has so far not shown to improve overall and
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