Correlation Between Gene Status and MYCN Protein Expression in Neuroblastoma: A Pilot Study To Propose the Use of MYCN Immunohistochemistry in Limited-Resource Areas.

PURPOSE

The most significant adverse risk factor for neuroblastoma (NB) is gene amplification, which strongly associates with high-risk disease. Fluorescent in situ hybridization (FISH) is considered the best method to evaluate gene status. However, it requires a laboratory that can perform highly complex testing, specialized personnel, and costly reagents. Herein, we aimed to investigate the feasibility of using immunohistochemistry (IHC) to detect MYCN protein expression in lieu of FISH, a strategy potentially useful in areas with limited resources.

METHODS

A pilot cohort of 78 patients with NB, including 34 of Middle Eastern descent (MED) who had a higher prevalence of gene amplification (44.11%) and 44 of North American descent (NAD), nine (20.45%) of whom had amplification, was evaluated with IHC for MYCN protein. Correlations of FISH results and protein expression are presented.

RESULTS

A positive correlation between gene amplification and protein expression by IHC was seen in 22 (91.66%) of the 24 -amplified NB cases-14 (93.33%) of 15 patients of MED and eight (88.88%) of nine patients of NAD. Agreement between negative FISH and negative IHC results was noted in 18 (94.73%) patients of MED and 34 (97.14%) patients of NAD. Two cases had weak protein expression but no gene amplification (MED: n = 1; 5.0%; NAD: n = 1; 2.9%).

CONCLUSION

An excellent overall correlation between gene status by FISH and MYCN protein expression by IHC was confirmed. MYCN IHC in NB with reflexing to FISH in equivocal cases is potentially useful in a limited-resource setting. Evaluation of effectiveness using a larger cohort and optimization to perform MYCN IHC manually is needed.