Prognostic Value of IGF2 mRNA-Binding Protein 3 (IGF2BP3) Intratumoral Expression in Melanoma Patients at the Time of Diagnosis: Comparative Analysis of RT-qPCR Versus Immunohistochemistry

SIMPLE SUMMARY: Around 80% of skin cancer deaths are due to melanoma. An accurate prognosis of melanoma clinical behavior from primary tumors is important for therapeutic patient management, currently based on histopathological features. The aim of our retrospective study was to investigate the clinical significance of IGF2BP3 mRNA and protein expression in melanoma progression and to evaluate which quantification method, RT-qPCR or immunohistochemistry, provides a more reliable prognostic value of IGF2BP3 expression in primary tumors. We found that IGF2BP3 mRNA expression correlated better with clinicopathologic melanoma features than the corresponding proteins and that patients with higher IGF2BP3 mRNA levels were at more risk for earlier development of metastasis, confirming its impact on melanoma survival. Our findings support the use of IGF2BP3 mRNA levels as an independent prognostic biomarker and the implementation of its RT-qPCR analysis for routine melanoma assessment, even for the earliest stages, to improve melanoma clinical outcomes and individualized treatment. ABSTRACT: Screening for prognostic biomarkers is crucial for clinical melanoma management. Insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) has emerged as a potential melanoma diagnostic and prognostic biomarker. It is commonly tested by immunohistochemistry (IHC). Our study retrospectively examines IGF2BP3 mRNA and protein expression in primary melanomas, their correlation with clinicopathologic factors, clinical outcome, and selected miRNAs expression, and their efficiency in predicting melanoma progression and survival. RT-qPCR and IHC on IGF2BP3 expression were performed in 61 cryopreserved and 63 formalin-fixed paraffin-embedded primary melanomas, respectively, and correlated to clinicopathologic factors, distant metastasis-free survival (DMFS), and melanoma -specific survival (MSS). The correlation between RT-qPCR and IHC was significant but moderate. IGF2BP3 mRNA showed a stronger association with clinicopathologic factors (Breslow thickness, ulceration, mitosis rate, growth phase, development of metastasis, and melanoma-specific survival) than its protein counterpart. Interestingly, higher IGF2BP3 mRNA expression was detected in primary melanomas that further metastasized to distant sites and was an independent prognostic factor for the risk of unfavorable DMFS and MSS. RT-qPCR outperformed IHC in sensitivity and in predicting worse clinical outcomes. Therefore, RT-qPCR may successfully be implemented for routine IGF2BP3 assessing for the selection of melanoma patients with a higher risk of developing distant metastasis and dying of melanoma.