Correlation of MYCN amplification with MCM7 protein expression in neuroblastomas: a chromogenic in situ hybridization study in paraffin sections.
Amplification of the MYCN oncogene in neuroblastomas is generally associated with a more aggressive clinical course. Recently, 1 of the minichromosome maintenance proteins, MCM7, was found to be a direct target of the MYCN transcription factor in neuroblastoma. To confirm this correlation, chromogenic in situ hybridization (CISH) to detect MYCN amplification and immunohistochemical staining for MCM7 protein expression were performed on paraffin tissue sections of 26 neuroblastomas cases and of 4 recurrences of these tumors. Seven of the primary tumors showed MYCN amplification, and all were stage 3 or 4 tumors. Only 4 of these showed MCM7 overexpression. However, 11 primary tumors overexpressed MCM7. The 4 patients with MCM7 expression associated with MYCN amplification all died from the tumor. In contrast, the 7 patients with MCM7 overexpression but no MYCN amplification were all younger than 1 year of age and have shown good survival. This suggests that MCM7 overexpression by itself is not related to a poorer prognosis as is MYCN amplification. In addition, the 4 pairs of primary and recurrent tumors all showed changes in MCM7 expression from negative to positive, whereas none of them had MYCN amplification. This study showed that MCM7 overexpression is not necessarily correlated with MYCN amplification or an aggressive clinical course. Interpretation of the results of CISH was quite easy and straightforward because the preparations were viewed with an ordinary light microscope with good preservation of the tissue morphology.
Tsai
Hsien-Yu
HY
Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei, Taiwan.
Hsi
Bae-Li
BL
Hung
Iou-Jih
IJ
Yang
Chao-Ping
CP
Lin
Jer-Nan
JN
Chen
Jeng-Chang
JC
Tsai
Shih-Feng
SF
Huang
Shiu-Feng
SF
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D064168:Minichromosome Maintenance Complex Component 7; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016612:Paraffin Embedding
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7