The Oncofetal Protein IMP3: A Novel Molecular Marker to Predict Aggressive Meningioma

Abstract

N Context.-One of the major clinical challenges is to predict recurrence of meningioma. Recently, we have found that IMP3, an oncofetal RNA-binding protein, is a biomarker to predict aggressive tumors.Objective.-To investigate whether IMP3 can be used as a new biomarker to predict the recurrence and overall survival of patients with meningiomas.Design.-One hundred seven patients with primary meningiomas were investigated for expression of IMP3 by immunohistochemistry and whether expression of this molecule correlated with tumor recurrence and overall survival.Results.-Tumor recurrence was found in 13 of 107 patients with primary meningioma. Seven of 107 patients (6.5%) with primary meningiomas expressed IMP3. Kaplan-Meier plots and log-rank tests showed that patients with IMP3-positive tumors had a much higher recurrence rate (P = .004) and a poorer overall survival (P , .001) than did patients with IMP3-negative tumors. The 5-year recurrence-free and overall survival rates were 0% and 36% in IMP3-positive patients versus 89% and 94% in IMP3-negative patients, respectively. Multivariable analysis of IMP3 status (positive versus negative) in primary tumors showed a hazard ratio of 17.89 for recurrence (P = .01), which was much higher than hazard ratios associated with all other known risk factors including higher tumor grades and Ki-67 labeling index.Conclusions.-IMP3 is a potential independent prognostic biomarker that can be used at the time of initial diagnosis of meningioma to identify patients who have a high risk of developing a recurrence.

IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma

“…Like p53 expression, tumors with high Ki-67 PI more frequently showed IMP3 expression. This observation has been documented in other tumors like hepatocellular carcinoma, B cell lymphoma, meningioma, and bile duct carcinoma 14,27,28,29. With these findings, IMP3 is considered to be a better prognostic marker than p53 or Ki-67 and these three proteins may be closely connected.…”

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

“…It has been shown that positive IMP3 immunohistochemical expression is of significant prognostic value in renal cell carcinoma, pancreatic ductal carcinoma, hepatocellular carcinoma, colonic adenocarcinoma, gastric adenocarcinoma, endometrioid adenocarcinoma, Merkel cell carcinoma, non-small cell lung cancer, meningioma, urothelial carcinoma, and mammary carcinoma, with an increased risk of developing metastases in patients with IMP3-positive tumors versus IMP3-negative tumors and an increased frequency of IMP3 expression in high-grade tumors versus low-grade tumors [6,12,14,19,27,28,32,35,42,[57][58][59][60][61][62][63]66]. In addition, IMP3 was found to be expressed more often in triple-negative (estrogen receptor, progesterone receptor, HER2) invasive mammary carcinomas than in non-triple-negative tumors [67].…”

Molecular Targets and Treatment of Meningioma

“…Other genetic non-NF2 aberrations of oncogenes have been observed in skull base and higher-grade meningiomas [12,[24][25][26]. The Glu17Lys mutation of the AKT1 (chromosome 14q32.32) gene was one of the mutations found in tumor cell lines that had no genetic alterations in the NF2 gene.…”

“…This causes an over active Akt kinase (protein kinase B) which excessively phosphorylates factors of the AKT/PKB pathway when it should be in the "off" position. This leads to an increase in the level of YAP that potentially can suppress the expression of pro-apoptotic genes that activate after cellular DNA damage [12,[23][24][25][26]. The GADD45A was once thought to be a potential genetic target for meningioma and other tumor pathogenesis; however, no genetic abnormalities were found in meningioma cell lines.…”

“…The GADD45A was once thought to be a potential genetic target for meningioma and other tumor pathogenesis; however, no genetic abnormalities were found in meningioma cell lines. The IMP3 gene is another gene of interest because the IMP3 protein has been identified as a biomarker for the aggressiveness of tumors [26]. Mutations in chromosome 9 also has been linked to meningioma proliferation mainly WHO Grade III meningiomas.…”