Diagnostic accuracy of HNF1β, Napsin A and P504S/Alpha-Methylacyl-CoA Racemase (AMACR) as markers of endometrial clear cell carcinoma

Abstract

Endometrial clear cell carcinoma (CCC) shows morphological overlap with endometrioid and serous carcinoma. We aimed to assess the accuracy of immunohistochemical diagnostic markers of CCC, i.e. HNF1β, Napsin A and P504S/Alpha-Methylacyl-CoA Racemase (AMACR). A systematic review and meta-analysis was conducted by searching 4 electronic databases from their inception to April 2022 for all studies assessing HNF1β, Napsin A and/or AMACR in endometrial CCC vs endometrioid/serous carcinomas. Diagnostic accuracy was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on sROC curves. Eleven studies were included. HNF1β positivity (any expression) showed sensitivity= 0.78; specificity= 0.81; LR+ =2.46; LR-= 0.38; DOR= 5.96; AUC= 0.79. Diffuse HNF1β expression showed sensitivity= 0.53; specificity= 0.95; LR+ =9.68; LR-= 0.51; DOR= 18.02; AUC= 0.40. Napsin A positivity (any expression) showed sensitivity= 0.76; specificity= 0.97; LR+ =18.79; LR-= 0.27; DOR= 73.31; AUC= 0.81. Diffuse Napsin A expression showed sensitivity= 0.52; specificity= 0.99; LR+ =14.50; LR-= 0.55; DOR= 24.93; AUC= 0.98. AMACR positivity (any expression) showed sensitivity= 0.76; specificity= 0.86; LR+ =4.86; LR-= 0.30; DOR= 13.56; AUC was not assessable due to the presence of only 2 studies. In conclusion, HNF1β, Napsin A and AMACR show moderate accuracy in identifying endometrial CCC. Considering only a diffuse expression of these markers as positive leads to high specificity but low sensitivity. In particular, Napsin A appears as the most specific marker of endometrial CCC.

Keywords: Clear cell carcinoma; Endometrial carcinoma; HNF1β; Napsin; Racemase.