Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma

Abstract

Background: MYCN gene amplification is a powerful indicator of poor prognosis of neuroblastoma patients. However, MYCN non-amplified patients still showed heterogeneity in survival outcome. This study aimed to investigate the prognostic role of MYCN immunohistochemistry (IHC) in pre-treatment and post-treatment neuroblastoma tumors. Methods: 215 untreated neuroblastoma tumors were stained with anti-MYCN antibody by immunohistochemical staining. 22 post-treatment tumors were used to compare MYCN staining with paired pre-treatment samples. Results were analyzed with other prognostic indicators. Results: Moderate or strong expression of MYCN was associated with unfavorable survival outcomes ( P < .001). Prominent staining of MYCN IHC was 95% sensitive and 95% specific for the presence of MYCN gene amplification in this study. Ten of 214 (5%) patients showed prominent MYCN staining but MYCN non-amplification, and had a poor prognosis (29.6 ± 16.4%, 5-year overall survival). Most of cases (7/11, 64%) with high or moderate MYCN expression before chemotherapy showed lower expression in their tumors after chemotherapy. Conclusion: MYCN protein overexpression was not only a sensitive and specific marker for MYCN gene amplification, but also a marker of poor prognosis in patients without MYCN amplification. However, MYCN protein expression was not always consistent before and after treatment.

Is MYCN Overexpression Associated With Poor Outcome in MYCN Non-Amplified Neuroblastomas?

“…We read with interest the recent manuscript by Zhao et al 1 describing the association of prominent MYCN protein expression with poorer clinical outcome in neuroblastomas without MYCN amplification. This report prompted us to conduct a quality assessment of this marker for potential use at our institution.…”

Wnt/β-Catenin Signaling Pathway in Pediatric Tumors: Implications for Diagnosis and Treatment

“…It presents with different clinical symptoms and is usually diagnosed at a later stage when the tumor has metastasized. Although the overall five-year survival rate is 75%, but it is less than 45% in high-risk neuroblastoma that represent about 40% of patients [ 20 , 41 , 42 ]. Amplification of the MYCN gene is associated with poor prognosis and low survival rate.…”

Author(s)’ Reply: Is MYCN Overexpression Associated With Poor Outcome in MYCN Non-Amplified Neuroblastomas?

“…According to their statements, a notable 59% of tumors exhibited MYCN expression, a percentage significantly surpassing both our findings and those reported in other studies. [1][2][3] We posit that this discrepancy may stem from a potential overestimation of MYCN staining results attributable to their utilization of a higher concentration of anti-MYCN antibodies (1:100). Consequently, we advocate for their consideration of employing a diminished antibody concentration, such as 1:150 or 1:200.…”

“…Andrews and Terry for their interest and pertinent comments on our article concerning MYCN immunohistochemistry in neuroblastomas. 1 Owing to the absence of comprehensive information, encompassing MYCN staining figures, the prevalence of high-risk neuroblastomas, and the therapeutic approach employed for their patient cohort, a precise evaluation of their findings proves challenging. According to their statements, a notable 59% of tumors exhibited MYCN expression, a percentage significantly surpassing both our findings and those reported in other studies.…”