AMOUNT OF PREOPERATIVE ENDOMETRIAL TISSUE 39 2 To our knowledge, this is the first study that quantified the amount of endometrial tissue surface by computerized measurement, and related this to the degree of concordance with final tumor grade and histological subtype in EC. The computerized assessment of the endometrial tissue surface was performed in a structured and reproducible fashion with a good interobserver agreement (ICC 0.92, 95% CI 0.80-0.97). As this was a retrospective study, one limitation could be that there has been no study protocol for the assessment of endometrial tissue. In addition, there might be a selection bias as the original diagnosis and classification of both pre- and postoperative histology was used without centralized pathology review. However, slides were from large referral hospitals and diagnoses were made by expert gynecological-pathologists. The results of this study are therefore applicable to daily practice and, as agreement is in line with previous findings, bias may be therefore considered to be limited. Finally, the small number of patients with serous EC (n=14, 2.4%) could limit the generalizability for this type of EC. Yet, serous carcinoma represents <10% of all ECs32. Also, it is known that there is poor interobserver agreement in differentiating serous EC from high-grade EEC based on preoperative histology.23, 24, 33-36 Although several studies support the use of a binary grading system (low- vs. high-grade) over the three-tiered FIGO grading system with respect to reproducibility, awareness of clinically relevant down- and upgrading remains crucial.9, 18, 35, 37, 38 Instead of providing more endometrial tissue, the use of a simple and relatively cheap set of IHC markers, such as p53 (reflecting the most aggressive molecular subgroup of the TCGA), ER/PR and L1CAM, could improve the concordance between pre- and postoperative low- and high-grade EC, and pre- and postoperative individual tumor grade and histological subtype.26, 39 According to the recent recommendations of the Society of Gynecologic Oncology (SGO), current clinicopathological prognostic parameters (e.g. histology and grade) should guide initial clinical management in EC. Molecular classification, especially TP53 mutations, may help guide future treatment decisions.8 In conclusion, obtaining a higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade classification in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome.
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