The Oncofetal Protein IMP3: A Novel Grading Tool and Predictor of Poor Clinical Outcome in Human Gliomas

Abstract

Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas.

<p>Insulin-like growth factor II mRNA-binding protein 3 promotes cell proliferation, migration and invasion in human glioblastoma</p>

“…In the present study, we found that high IMP3 expression was significantly correlated with high grade of glioma patients, and validated its high expression in glioma cells. Consistent with our data, Del Gobbo A et al suggested that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas, indicating that IMP3 may act as a novel grading tool and predictor of poor clinical outcome in human gliomas 16…”

The vacuolar H+ ATPase is a novel therapeutic target for glioblastoma

“…A first series consisted of 54 patients that underwent surgery between 2013 and 2014, of which both fresh and archival neoplastic tissue could be retrieved for molecular or histological analyses respectively (Gene expression series). A second set of 187 patients that consecutively underwent surgery between 2008 and 2010 was enrolled for retrospective investigations on formalin-fixed paraffin-embedded tissues (Tissue microarray series) as previously described [ 40 ]. All patients were treated with surgical resection of the lesion and nobody received a merely diagnostic procedure.…”

“…Following histological diagnosis, all patients affected by high grade gliomas (HGG; grades III and GBM) underwent concomitant chemo-radiation therapy according to the Stupp's protocol [ 42 ]. Follow-up data was available for GBM patients and it consisted of neuro-oncological assessment and brain MRI with gadolinium every 3 months as described [ 40 ]. Tumor progression was defined according to MacDonald's criteria [ 17 ].…”

“…The significance of a variable for GBM patients' prognosis was analyzed using the Cox regression hazard model either as univariate or multivariate analysis (MedCalc software, Mariakerke, Belgium) considering proteins IHC scores, MGMT methylation status, age at diagnosis, presence of IDH1 R132H mutation or tumor grade as categorical variables. To generate a cut-off for V-ATPase G1 IHC score we used receiver operating characteristics (ROC) curves and the non-arbitrary criterion derived from the Youden index (J, MedCalc Software) as described [ 40 ]. Glioma patients were then sorted into low or high-expressor categories.…”

IMMUNOHISTOCHEMICAL VALIDATION OF INSULIN-LIKE GROWTH FACTOR II mRNA-BINDING PROTEIN 3 (IMP3) AS A DIAGNOSTIC MARKER IN SALIVARY GLAND TUMORS

“…Insulin-like growth factor II mRNA-binding protein 3(IMP3) belongs to IMP family that consists of IMP1, IMP2, and IMP3. IMP family members have a significant role in RNA trafficking and stabilization, cell growth as well as cell migration during the early stages of embryogenesis (6). IMP3 is a protein encoded by gene IGF2BP3 which is located on chromosome 7p11.2 (7).…”