Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is a marker that predict presence of invasion in papillary biliary tumors

Publication date: Available online 13 January 2017
Source:Human Pathology
Author(s): Motoko Sasaki, Yasunori Sato
Biliary tumors showing intraductal papillary growth (Pap-BT) include intraductal papillary neoplasm of the bile duct (IPNB) and papillary cholangiocarcinoma (CC). A differential diagnosis between IPNB and papillary CC currently remains challenging. The aim of the present study is to identify histological features and immunohistochemical markers of malignant potential such as tumor invasion in Pap-BT. Subjects comprised 37 patients with Pap-BT (intrahepatic and perihilar (proximal), 27; 17 non-invasive and 10 invasive); distal 10, all invasive). We examined histological features and the expression of p53, enhancer of zeste homolog 2 (EZH2), insulin-like growth factor II mRNA-binding protein 3 (IMP3), and DNA methyltransferatse-1 (DNMT1) in the intraductal area in Pap-BT. Non-invasive Pap-BT was characterized by the presence of a low-grade dysplastic area, edematous stroma, and the absence of necrosis. The expression of p53, EZH2, IMP3 and DNMT1 was significantly weaker in non-invasive Pap-BT than in invasive Pap-BT (P<.01). Diffuse cytoplasmic IMP3 expression was absent in non-invasive Pap-BT. IMP3 showed the greatest specificity to predict a presence of invasion. A heatmap demonstrated that proximal non-invasive Pap-BT and distal Pap-BT may be completely different. In bile duct biopsies, the expression of IMP3 was the most precise predictor of invasion in Pap-BT. In conclusion, Pap-BT may be separated into 3 subgroups; 1) proximal non-invasive Pap-BT, corresponding to IPNB, 2) distal invasive pap-BT, corresponding to papillary CC and 3) the remaining Pap-BT including IPNB with associated adenocarcinomas, based on histological and immunohistochemical features. IMP3 may be a useful marker for predicting invasion in Pap-BT.



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