Addition of IMP3 to L1CAM for discrimination between low- and high-grade endometrial carcinomas: an ENITEC collaboration study

Summary Discrimination between low- and high-grade endometrial carcinomas (ECs) is clinically relevant, but can be challenging for pathologists with moderate interobserver agreement. Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is an oncofoetal protein that is associated with non-endometrioid endometrial carcinomas, but has been limited studied in endometrioid carcinomas. The aim of this study is to investigate the diagnostic and prognostic value of IMP3 in the discrimination between low- and high-grade ECs, and its added value to L1CAM. IMP3 and L1CAM expression was assessed in tumors from 378 patients treated for EC at one of nine participating ENITEC centres. IMP3 was expressed in 24.6% of the tumors. In general, IMP3 was more homogeneously expressed than L1CAM. IMP3 expression was significantly associated with advanced stage, non-endometrioid histology, grade 3 tumors, deep myometrial invasion, lymphovascular space invasion (LVSI), distant recurrences, overall mortality, and disease-related mortality. Simultaneous absence of IMP3 and L1CAM expression showed the highest accuracy for identifying low-grade carcinomas (AUC 0.766), whereas simultaneous expression of IMP3 and L1CAM was strongly associated with high-grade carcinomas (OR 19.7; 95% CI 9.2–42.2). Even within endometrioid carcinomas, this combination remained superior to IMP3 and L1CAM alone (OR 8.6; 95% CI 3.4–21.9). In conclusion, IMP3 has good diagnostic value and together with L1CAM represents the optimal combination of diagnostic markers for discrimination between low- and high-grade ECs compared to IMP3 and L1CAM alone. Because of the homogenous expression of IMP3, this marker might be valuable in preoperative biopsies when compared to the more patchy L1CAM expression.