Analysis of IMP3 Expression in Normal and Neoplastic Human Pituitary Tissues

Abstract

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. In various tumors, IMP3 expression is correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in pituitary tumors. We analyzed the immunohistochemical expression of IMP3 in five normal pituitary tissues and 75 pituitary tumors (64 adenomas and 11 carcinomas) to determine if specific tumor types expressed IMP3 and if there were differences in IMP3 expression between adenomas and carcinomas. Immunohistochemical analysis showed that IMP3 was positive in four (80%) normal pituitaries with focal stain in a subset of normal anterior pituitary cells. IMP3 was expressed in 31% (20/64) of adenomas and in 36% (4/11) of carcinomas. A slightly higher level of IMP3 expression was observed in PRL-GH-TSH adenomas compared to the other types of pituitary adenomas. Expression of IMP3 was not significantly higher in carcinomas than in adenomas (p = 0.737). RT-PCR and Western Blotting supported the heterogeneous expression of IMP3. These results indicate that IMP3 is expressed both in normal and in neoplastic pituitary gland tissues without significant differences in expression levels in pituitary carcinomas.

The use of insulin like-growth factor II messenger RNA binding protein–3 in diagnostic pathology

“…The utility of molecular methodologies, such as RT-PCT, must also be considered. In studies that have examined IMP3 expression via both immunohistochemistry and RT-PCR, there has been great concordance between the 2 different methodologies [12,15,28,55,59,80]. Quantitative RT-PCR has been used in the examination of IMP3 expression in renal cell carcinoma and has demonstrated an overexpression of IMP3 mRNA in tumors that subsequently metastasized, as compared with immunohistochemically IMP3-negative primary tumors that did not metastasize [59].…”

“…During embryogenesis, the greatest expression of IMP3 occurs in the gut, pancreas, kidney, and brain [8]. Expression of IMP3 in adults is normally limited to placental intermediate trophoblasts, with limited expression in lymph node germinal centers, ovary, testis, brain, the internal root sheath of hair follicles, and intestinal and endocervical mucosa [2,8,[10][11][12][13][14][15][16]. IMP3 is encoded by the IGF2BP3 gene located on chromosome 7p11.2 [17].…”

“…Table 1 outlines the reported frequencies of IMP3 expression in human malignancies, either by immunohistochemistry or reverse transcription polymerase chain reaction (RT-PCR) studies. IMP3 is expressed in a variety of tumors with variable positivity, including pancreatic adenocarcinoma, esophageal adenocarcinoma, melanoma, gallbladder carcinoma, serous endometrial carcinoma, Hodgkin lymphoma, pulmonary and extrapulmonary small cell carcinoma, pulmonary large cell neuroendocrine carcinoma, Merkel cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, gastric adenocarcinoma, ovarian carcinoma, non-small cell lung cancer, follicular thyroid carcinoma, laryngeal squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma of the bladder, osteosarcoma, malignant pleural mesothelioma, meningioma, pituitary adenoma, and pituitary carcinoma [6,9,[11][12][13][14][15][16][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][39][40][41][42][43][44][45][46][47][48][49][50][51][52]…”

Value of glut-1 and koc markers in the differential diagnosis of reactive mesothelial hyperplasia, malignant mesothelioma and pulmonary adenocarcinoma

“…KOC (K homology domain-containing protein), commonly known as IMP3 (insulin-like growth factor 2 mRNA binding protein 3) in the literature, is an oncofetal RNA-binding protein (20)(21)(22)(23). Th e IMP family plays an important role in the stabilization of mRNA, cell growth, cell proliferation and cell migration during the early stages of embryogenesis (21,22,24,25).…”

IMP3 and Malignant Melanoma

“…After embryogenesis and development, IMP3 expression is detectable in occasional adult tissues, including the internal root sheath of hair follicles, germinal centers of lymph nodes ( Figure 1B), patchy gastrointestinal tract and bronchiolar epithelium (Righi, Zhang et al;Mueller-Pillasch, Pohl et al 1999;Nielsen, Christiansen et al 1999;Hammer, Hansen et al 2005;Simon, Bourne et al 2007;Xu, Bourne et al 2007;Mentrikoski, Ma et al 2009). In addition to its expression in fetal development, IMP3 has been detected in numerous malignancies including germ cell carcinomas, renal cell carcinoma, small and non-small cell lung carcinomas, urothelial carcinoma, endometrial serous and cervical carcinomas, Merkel cell carcinoma, extrapulmonary small cell carcinoma, various lymphomas, thyroid carcinoma, mammary breast carcinoma, colonic, gastric and esophageal adenocarcinomas, and osteogenic sarcoma (Asioli, Erickson et al ;Findeis-Hosey, Yang et al ;Jin, Seys et al ;Righi, Zhang et al ;Wang, Fan et al 2003;Hammer, Hansen et al 2005;Jiang 2007;Li, Rock et al 2007;Simon, Bourne et al 2007;Do, Kim et al 2008;Li, Xu et al 2008;Pryor, Bourne et al 2008;Zheng, Yi et al 2008;Jeng, Wang et al 2009;King, Pasha et al 2009;Li, Yan et al 2009;Li, Huang et al 2009;Lu, Vohra et al 2009;Mentrikoski, Ma et al 2009;Pryor, Simon et al 2009;Slosar, Vohra et al 2009;Walter, Prasad et al 2009;Yuan, Wang et al 2009). Moreover, IMP3 expression has been shown to be a marker of poorer prognosis with decreased overall survival in several tumors including renal cell carcinoma, mammary breast carcinoma, non-small cell lung carcinoma, and numerous gastrointes...…”