Evaluation of Ki-67 as prognostic factor for pediatric neuroblastoma and the possibility of molecular-targeted drugs with VEGF and PDGFR.

Abstract

BACKGROUND:

Neuroblastoma (NB) is a pediatric malignant solid tumor characterized as refractory cancer with poor prognosis. The Mitosis-Karyorrhexis Index (MKI) is a prognostic factor but is prone to observer bias. The usefulness of MKI with Ki-67, as a marker of malignancy, was investigated. The efficacy of molecular-targeted therapeutic agents with fewer side effects in tumors has been studied. Molecular-targeted therapy targets include vascular endothelial growth factor (VEGF), involved in tumor angiogenesis; c-Kit, receptor of Kit/stem cells involved in tumor growth, vasculature, and lymphangiogenesis; platelet-derived growth factor receptor (PDGFR); and B-Raf proto-oncogene, serine/threonine kinase (BRAF), involved in the RAS protein-mediated mitogen-activated protein kinase pathway. Therefore, expression profiles of these factors and growth inhibitory effects of molecular-targeted drugs against NB were investigated.

METHODS:

Ten frozen NB tissue samples collected from January 1993 to December 2017 were evaluated immunohistochemically for Ki-67 and VEGF. c-Kit, PDGFR, and BRAF expression levels were evaluated using enzyme-linked immunosorbent assays; relationships between these factors and clinicopathological parameters of NB were analyzed.

RESULTS:

Eight patients with NB showed no amplification of MYCN (MYCN proto-oncogene, bHLH transcription factor). There were two cases of ganglioneuroblastoma (GNB). More NB cells were positive for Ki-67 than for GNB cells. VEGF expression was observed in all NB specimens and was stronger in stage IIB and higher. No BRAF or c-Kit activity was observed; PDGFR activity was greater in NB than in GNB (P=0.02).

CONCLUSIONS:

Thus, Ki-67 may help evaluate NB malignancy. As the first therapy for NB prevents amplification of MYCN, agents targeting PDGFR as well as VGFG can inhibit NB cell proliferation.

• Authors: Shunsuke Watanabe, Tatsuya Suzuki, Yasuhiro Kondo, Atsuki Naoe, Naoko Uga, Toshihiro Yasui, Fujio Hara, Tomonori Tsuchiya
• Journal: Minerva pediatrics (Minerva Pediatr (Torino)) Vol. 75 Issue 4 Pg. 561-566 (08 2023) ISSN: 2724-5780 [Electronic] Italy
• PMID: 30605998 (Publication Type: Journal Article)

Chemical References

• Vascular Endothelial Growth Factor A
• Ki-67 Antigen
• Receptors, Platelet-Derived Growth Factor
• N-Myc Proto-Oncogene Protein
• Vascular Endothelial Growth Factors
• Receptor Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-kit

Topics

• Child
• Humans
• Vascular Endothelial Growth Factor A (metabolism)
• Ki-67 Antigen (genetics)
• Receptors, Platelet-Derived Growth Factor
• Prognosis
• N-Myc Proto-Oncogene Protein
• Neuroblastoma (drug therapy, metabolism, pathology)
• Vascular Endothelial Growth Factors
• Ganglioneuroblastoma (metabolism, pathology)
• Receptor Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-kit