Endometrial Adenocarcinoma Biopsies: Can Targeted Education Increase Reproducibility and Is It a Good Idea?

Abstract

Abstract Introduction/Objective Assessing p53 mutation on biopsies could provide prognostic and therapeutic planning information, as it predicts worse outcomes for patients with endometrioid adenocarcinoma (EA). Immunohistochemistry (IHC) mutation pattern staining varies, easily causing misinterpretation. This study was designed to see if education clarifying staining issues would increase reproducibility, and if mutations detected in this setting were of prognostic import. Methods/Case Report p53 IHC on 46 FIGO grade 1 EA biopsies was scored by blinded participants. Education was provided regarding internal controls (IC), and common misinterpretations. The participants rescored to assess reproducibility. Outcome parameters (clinical stage [CS], progression free survival, higher FIGO grade on resection, and presence of mismatch repair mutations) were also assessed. Results (if a Case Study enter NA) 25% of scores changed post-education. Intraclass correlation among raters was 0.29 pre and 0.43 post (from fair to moderate). Mutation status changed in 5 cases. 2/5 caught IC failure for 1 case. Post-participation surveys found 0 participants were previously familiar with “high wild type,” and 60% were unfamiliar with cytoplasmic staining pattern, the possibility for heterogeneity, and necessary ICs. Every participant agreed grading was easier following education. Out of 6 patients with high CS disease (IIIC-IV), none had p53 mutation. 2/11 cases with higher FIGO grade (2-3) on resection had mutation. One patient had recurrence with no detectable mutation. 15/46 patients had MMR results available. No p53 mutation was detected in those with a loss of MLH1 and PMS2 (n=8). Conclusion Education on IHC issues can increase reproducibility in scoring, though overall reproducibility on biopsies was still subpar. Mutation detected in this setting did not correlate with current outcome parameters. Given the possibility of heterogenous expression and difficulties interpreting edge effect and assessing ICs in scant specimens, p53 IHC on EA biopsies is not recommended.