Whole proteome analysis of mesonephric-derived cancers describes new potential biomarkers

Mesonephric carcinomas (ME) and female adnexal tumours of probable Wolffian origin (FATWO) are derived from embryologic remnants of Wolffian/mesonephric ducts. Mesonephric-like carcinomas (MLC) show identical morphology to ME of the cervix, but occur in the uterus and ovary without convincing mesonephric remnants. ME, MLC and FATWO are challenging to diagnose due to their morphologic similarities to Mullerian/paramesonephric tumours, contributing to a lack of evidence-based and tumour-specific treatments. We performed whole proteomic analysis on 9 ME/MLC and 56 endometrial carcinomas (EC) to identify potential diagnostic biomarkers. While there were no convincing differences between ME and MLC, 543 proteins showed increased expression in ME/MLC relative to EC. From these proteins, EHMT2, GSTM3, EEF1A2, and GSK3β were identified as putative biomarkers. Immunohistochemistry was performed on these candidates at GATA3 in 14 ME/MLC, 8 FATWO, 155 EC, and normal tissues. Of the candidates, only GATA3 and EHMT2 were highly expressed in mesonephric remnants and mesonephric-derived male tissues. GATA3 had the highest sensitivity and specificity for ME/MLC versus EC (93% and 99%), but was absent in FATWO. EHMT2 was 100% sensitive for ME/MLC & FATWO, but was not specific (65%). Similarly, EEF1A2 was reasonably sensitive to ME/MLC (92%) and FATWO (88%), but was the least specific (38%). GSTM3 performed intermediately (sensitivity for ME/MLC and FATWO: 83% and 38% respectively; specificity 67%). While GATA3 remained the best diagnostic biomarker for ME/MLC, we have identified EHMT2, EEF1A2, and GSTM3 as proteins of interest in these cancers. FATWO's cell-of-origin is uncertain and remains an area for future research.