Santiago Teresa, Tarek Nidale, Boulos Fouad, Hayes Caleb, Jeha Sima, Raimondi Susana, Rodriguez-Galindo Carlos
St Jude Children's Research Hospital, Memphis, TN.
American University of Beirut Medical Center, Beirut, Lebanon.
J Glob Oncol. 2019 Jul;5:1-7. doi: 10.1200/JGO.19.00135.
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.
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.
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%).
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.
神经母细胞瘤（NB）最显著的不良风险因素是基因扩增，其与高危疾病密切相关。荧光原位杂交（FISH）被认为是评估基因状态的最佳方法。然而，它需要一个能够进行高度复杂检测的实验室、专业人员和昂贵的试剂。在此，我们旨在研究使用免疫组织化学（IHC）检测MYCN蛋白表达以替代FISH的可行性，这一策略在资源有限的地区可能有用。
对78例NB患者的试点队列进行评估，其中包括34例中东血统（MED）患者（基因扩增患病率较高，为44.11%）和44例北美血统（NAD）患者（其中9例[20.45%]有基因扩增），通过IHC检测MYCN蛋白。呈现了FISH结果与蛋白表达的相关性。
在24例基因扩增的NB病例中的22例（91.66%）——15例MED患者中的14例（93.33%）和9例NAD患者中的8例（88.88%）——观察到基因扩增与IHC检测的蛋白表达呈正相关。在18例（94.73%）MED患者和34例（97.14%）NAD患者中，FISH阴性与IHC阴性结果一致。有2例蛋白表达较弱但无基因扩增（MED：n = 1；5.0%；NAD：n = 1；2.9%）。
证实了FISH检测的基因状态与IHC检测的MYCN蛋白表达之间总体相关性良好。在NB中进行MYCN IHC检测，在可疑病例中结合FISH检测，在资源有限的情况下可能有用。需要使用更大的队列评估有效性，并优化以手动进行MYCN IHC检测。
