Usefulness of insulin-like growth factor II mRNA-binding protein 3 (IMP3) as a new marker for the diagnosis of esophageal adenocarcinoma in challenging cases

Abstract

Background/Aims: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein with vital function during human embryogenesis in terms of cellular growth and migration. Although it has minimum and undetectable expression in human adult tissues, it is highly expressed in various types of cancer. Few studies have recommend application of IMP3 expression to diagnose challenging cases of esophageal adenocarcinoma. This survey was aimed to evaluate the benefit of IMP3 expression detection in the diagnosis of esophageal adenocarcinoma and high-grade dysplasia by using immunohistochemistry (IHC). Materials and Methods: An immunohistochemistry study of IMP3 oncofetal protein was performed on paraffinembedded blocks of 76 cases, including Barrett's esophagus, esophageal squamous epithelium, Barrett's esophagus with low-grade dysplasia, Barrett's esophagus with high-grade dysplasia, moderately differentiated esophageal adenocarcinoma, and poorly differentiated esophageal adenocarcinoma. Two pathologists reevaluated the diagnosis and evaluated the positivity and intensity of the IHC staining as well. Results: Insulin-like growth factor II mRNA-binding protein 3 expression was intensely positive in all cases of esophageal adenocarcinoma and Barrett' s esophagus with HGD. Only mild positivity in 30% of Barrett' s esophagus with LGD was seen. However, Barrett' s esophagus and esophageal squamous epithelium had, in fact, no IMP3 expression. Conclusion: The percentage and intensity of IP3 IHC staining showed a significant difference between highgrade dysplasia and adenocarcinoma versus Barrett's esophagus with low-grade dysplasia, Barrett's esophagus, and esophageal squamous epithelium. Therefore, IMP3 oncofetal protein could be a very useful marker for the diagnosis of high-grade dysplasia and adenocarcinoma. However, to test the validation, a larger number samples is required.

IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

“…The overexpression of IGF2BP3 may therefore be a supplement to the diagnosis of HGIN, especially in challenging cases. 15 Overall, our results suggest a potential tissue marker for the diagnosis of HGIN and provide a complementary strategy to histopathologic examination. A large sample will be enrolled for further test validation.…”

“…The positive rate of IGF2BP3 in squamous cell carcinoma of the skin, 16 the head and neck, 1 , 17 and the tongue 18 were 57%, 61%, and 77%, respectively. According to the study by Kazeminezhad et al, 15 the positive rate of IGF2BP3 was about 91% in advanced esophageal adenocarcinoma. In the study by Yantiss et al, 21 IGF2BP3 was with a 97% positive rate in pancreatic adenocarcinoma.…”

“…The overexpression of IGF2BP3 has been reported in some tumors, 9 – 13 , 15 – 19 including ESCC, and has been reported to be involved in cell proliferation, invasion, and the advanced disease stage. In squamous epithelial tumors, 9 , 16 – 19 IGF2BP3 has been claimed as a potential marker for diagnosis.…”

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

“…Some other studies have reported higher expression of hnRNP‐B1 (Matsuyama et al, ) and ‐H1 (Sun, Liu, Liu, & Zhao, ), NF45 (Ni et al, ), insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP)‐2 (Barghash, Golob‐Schwarzl, Helms, Haybaeck, & Kessler, ) and ‐3 (W. Feng et al, ; Kazeminezhad, Mirafsharieh, Dinyari, Azizi, & Ebrahimi, ; Trivedi, Cartun, & Ligato, ), DEAD‐Box Helicase 46 (B. Li, Li, et al, ), and Musashi‐1 (Mokrowiecka et al, ) in EC tissues. Because enhanced expression of these molecules was correlated with poor pathologic features and worse survival of patients, they are thought to be useful as new prognostic markers and potential anticancer targets in EC.…”

IGF2 mRNA binding protein 3 (IMP3) promotes glioma cell migration by enhancing the translation of RELA/p65

“…While, recent evidence associates derailed expression or activity of these RBPs with several genetic diseases including cancer, their cellular target repertoire, how they regulate the transcriptome and proteome and whether they can be used for therapeutic intervention warrants further investigation [8–11]. IMP3 is an example of an oncofetal RNA binding protein, which has been associated with various malignancies [12–16]. Few of the bonafide targets of the protein are emerging from the recent research [9].…”