[Abnormality of TOP2A expression and its gene copy number variations in neuroblastic tumors].
Objective:To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors (NT).Methods:Immunohistochemistry was used to detect TOP2A protein expression. Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A.Results:TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation (P=0.006), Ki-67 index (P<0.01) and MKI (P=0.001). Twenty-eight cases (35.0%, 28/88) showed TOP2A gene amplification, which was correlated with the age (P<0.01), clinical stage (P=0.028), high risk group (P=0.001), Ki-67 index (P=0.040) and differentiation (P=0.014). Survival analysis showed that TOP2A expression was related to survival rate. Multivariate analyses showed that TOP2A expression was an independent predictor for poor prognosis (P=0.010).Conclusions:More than half of the cases show TOP2A expression, which is more likely associated with NB, high Ki-67 index and high MKI. Cases with TOP2A expression have shorter survivals and poorer prognosis. TOP2A amplification is seen in 35% and likely occurs in patients older than 18 months and at advanced INSS stages (Ⅲ and Ⅳ). As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.
Department of Pathology, Capital Medical University, Beijing 100069, China.
J M
JM
Chen
C J
CJ
Zhou
X L
XL
Ma
D D
DD
Guan
L Y
LY
Yang
P
P
Yue
L P
LP
Gong
D000367:Age Factors; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms; D056915:DNA Copy Number Variations; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000075223:Poly-ADP-Ribose Binding Proteins; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human