Adjunctive diagnostic tool for histopathological classification of congenital mesoblastic nephroma based in molecular genetic findings

Purpose: Congenital mesoblastic nephromas (CMN) are histologically classified into classical, cellular, and mixed subtypes. Most cellular CMNs harbor ETV6-NTRK3 gene fusions, and classic and mixed CMNs harbor EGFR internal tandem duplications (EGFR-ITDs). Classic CMNs are considered benign, whereas recurrent or metastatic diseases occur in the cellular subtypes. Direct identification of mutations is desirable for an accurate diagnosis. However, molecular genetic analyses cannot be performed in a number of histopathology laboratories. This study aimed to investigate a surrogate marker for the accurate histological classification of CMN. Methods: Overall, 11 CMN cases diagnosed at our institute were included in this study. Reverse transcription-polymerase chain reaction was performed for the NTRK gene fusion and EGFR-ITDs in all cases. Comprehensive mRNA analysis was performed using the nCounter^® Gene Expression Assay. Principal component analysis (PCA) was performed based on the gene expression levels. Immunohistochemical evaluation was conducted for the expression of p-Mek1/2, p-Erk1/2, and EGFR. Results: PCA revealed differences in mutation patterns between the EGFR-ITDs and NTRK fusion tumor groups. Gene ontology analysis of the highly expressed genes in the EGFR-ITDs tumor group revealed enrichment related to the mitogen-activated protein kinase (MAPK) signaling pathway. p-Mek1/2 and p-Erk1/2 immunoreactivity was significantly increased in the EGFR-ITDs tumor group (p = 0.018 and p = 0.017, respectively). EGFR immunoreactivity is not a useful marker for CMN with EGFR-ITD. Conclusion: p-Mek1/2 and p-Erk1/2 immunoreactivity may be useful markers for EGFR-ITDs. Thus, MEK1/2 inhibitors possess the potential to be used as a targeted therapy for CMN with EGFR-ITDs.