ER+/PR+/TFF3+/IMP3- immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases

Aims Differentiating endometrioid adenocarcinoma (EAC) from uterine serous carcinoma (USC) and clear cell carcinoma (CCC) of the endometrium can be challenging. We undertook an immunohistochemical study to address this issue. Methods and results We evaluated 401 endometrial carcinomas cases by using four immunomarkers oestrogen receptor (ER), progesterone receptor (PR), insulin-like growth factor II mRNA binding protein 3 (IMP3), and intestinal trefoil factor 3 (TFF3)on a tissue microarray. The cases included 311 EACs (G1, 146; G2, 104; and G3, 61), 69 USCs, and 21 CCCs. ER, PR and TFF3 were most frequently expressed in EACs (P<0.001), and IMP3 was more frequently expressed in USCs and CCCs (P<0.001). ER+/PR+/TFF3+/IMP3 was the best marker combination associated with EAC [exact odds ratio (OR) 112; 95% confidence interval (CI) 19; P<0.0001]. This marker combination remained very reliable after adjustment for tumour grade (exact OR 19.2; 95% CI 3; P=0.0004). Because distinguishing EAC G3 from USC and CCC on the basis of morphology may be difficult, the use of immunomarkers to improve reproducibility is highly recommended. We found the ER+/PR+/TFF3+/IMP3 immunoprofile to be the best combination for confirming a diagnosis of endometrioid adenocarcinoma (exact OR 19.2; 95% CI 3; P=0.0004). Conclusions We recommend using an ER/PR/TFF3/IMP3 immunohistochemical panel in selected cases of endometrial carcinoma where the differential diagnosis is challenging.