ABSTRACT
Chromogranin A (CgA) and neuron specific enolase (NSE) are important markers in adult neuroendocrine tumors (NET). Neuroblastoma (NB) has certain neuroendocrine properties. The aim of this study was to correlate blood concentrations of CgA, chromogranin B (CgB), and NSE to prognostic factors and outcome in children with NB. Blood samples from 92 patients with NB, 12 patients with benign ganglioneuroma (GN), 21 patients with non-NB solid tumors, 10 patients with acute leukemias, and 69 healthy children, were analyzed. CgA concentrations were higher in neonates vs. children older than one month in the control group (p < 0.0001), and in neonates with NB vs. the control group (p < 0.01). CgA and NSE concentrations were higher in patients with stages 3 and 4 disease (p < 0.05 and p < 0.05), in patients having tumors with amplification of MYCN (p < 0.05 and p < 0.001), or chromosome 1 p deletion (p < 0.05 and p < 0.05). NSE correlated to the tumor size at diagnosis (p < 0.001) and to tumor related death (p < 0.01) in NB. CgA and NSE concentrations were elevated in patients with NB and especially in those with advanced disease. Both CgA and NSE correlated to genetic markers, while only NSE correlated to primary tumor size and outcome in NB. We found that CgA and NSE are clinically valuable tumor markers in NB and they merit prospective clinical evaluations as such.
Subject(s)
Biomarkers, Tumor/blood , Chromogranin A/blood , Neoplasm Proteins/blood , Neuroblastoma , Phosphopyruvate Hydratase/blood , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Male , Neoplasm Staging , Neuroblastoma/blood , Neuroblastoma/mortality , Retrospective Studies , Survival RateABSTRACT
AIM: To determine whether concentrations of the angiogenic growth factors hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A) correlate with clinical and genetic markers in samples taken at diagnosis in children with neuroblastoma (NB). PATIENTS AND METHODS: Heparin plasma (P-) and serum (S-) samples of healthy controls (n=73, mean age +/- SD 3.5+/-2.1; females/males: 23/50) and patients with NB (n=62; 2.2+/-1.8; 26/36) were collected between 1988 and 1999. Clinical data included age at diagnosis, gender, stage, outcome, amplification of the oncogene MYCN, loss of heterozygosity at the short arm of chromosome 1 (1p LOH) and ploidy. RESULTS: HGF and S-VEGF-A were elevated in NB as compared to controls (38/62 patients, p<0.0001 and p<0.05, Mann-Whitney U test). HGF concentrations were higher in high-stage (stage 3-4) as compared to low-stage (stage 1-2) disease (p<0.01). P-HGF was elevated in patients with 1p LOH (p<0.01), MYCN amplification (p<0.001) and di- or tetraploidy (p<0.001). S-HGF concentration was elevated in patients MYCN-amplified tumors only. Plasma and S-HGF concentrations were higher in the deceased group (p<0.05), but not P or S-VEGF-A. CONCLUSION: This study showed that concentrations of HGF and S-VEGF-A are elevated in patients with NB. Furthermore, HGF and S-VEGF-A concentrations correlate to higher stage disease and HGF correlates to genetic markers known to indicate a poor outcome. These observations imply that HGF and VEGF-A have biological roles in NB and suggest the possibility of interference with HGF or VEGF-A signaling as a therapeutic strategy.
Subject(s)
Hepatocyte Growth Factor/blood , Neuroblastoma/blood , Neuroblastoma/diagnosis , Vascular Endothelial Growth Factor A/blood , Case-Control Studies , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Infant, Newborn , Loss of Heterozygosity , Male , Multicenter Studies as Topic , N-Myc Proto-Oncogene Protein , Neuroblastoma/genetics , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Ploidies , PrognosisABSTRACT
BACKGROUND: Zoledronic acid is a new member of the bisphosphonate (BP) class of compounds, a family of closely related synthetic molecules originally derived from the naturally occurring pyrophosphate. These compounds that are potent inhibitors of bone resorption, have been shown to reduce the growth of several cancer cell lines in vitro, and can act as inhibitors of angiogenesis. The angiogenesis inhibitor TNP-470, a synthetic analogue of the fungal antibiotic fumagillin, has been shown to inhibit the growth of multiple tumors in vivo, and is currently in Phase II clinical trials for cancer. MATERIALS AND METHODS: The effects of daily subcutaneous (s.c.) administration of zoledronic acid (0.1 mg/kg) were compared with those of TNP-470 (15 mg/kg/day and 30 mg/kg every other day, s.c.) in a nude mouse xenograft model for the childhood cancer, neuroblastoma (NB). RESULTS: Zoledronic acid reduced the tumor growth by 33% whereas TNP-470 was less effective and reduced the tumor growth by 26% and 11% for animals treated with 15 mg/kg/day and 30 mg/kg every other day, respectively. Analysis of angiogenesis showed a significant reduction of the number of vessels per grid and in vessel length in all the treatment groups. CONCLUSION: Zoledronic acid shows tumoristatic and angiostatic properties that might be beneficial in the treatment of solid tumors such as neuroblastoma.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Diphosphonates/pharmacology , Imidazoles/pharmacology , Neuroblastoma/blood supply , Neuroblastoma/drug therapy , Animals , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Growth Processes/drug effects , Cell Line, Tumor , Cyclohexanes/pharmacology , Endothelial Cells/cytology , Endothelial Cells/drug effects , Female , Humans , Male , Mice , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Neuroblastoma/pathology , O-(Chloroacetylcarbamoyl)fumagillol , Sesquiterpenes/pharmacology , Xenograft Model Antitumor Assays , Zoledronic AcidABSTRACT
BACKGROUND/PURPOSE: The aims of this study were to evaluate the diagnostic accuracy and safety of cutting needle biopsy for diagnosis in children with tumors suspected for malignancy. METHODS: Medical records and biopsy slides recorded from 1988 to 1999 were reviewed. One hundred ten patients had undergone a total of 147 cutting needle biopsies. The biopsy was performed under ultrasound guidance, using a 1.2-mm (18 gauge) Biopsy-cut biopsy needle. The diagnoses were benign tumors (n = 8), malignant tumors (n = 84), and nonneoplastic diseases (n = 18), with repeat biopsy performed in 24 patients. RESULTS: The diagnostic accuracy of cutting needle biopsies was 89% (131 of 147). The accuracy for pretreatment diagnosis was 88% (102 of 116), and for confirming or excluding a recurrence or metastasis 93% (26 of 28). The sensitivity of this method was 82% (86 of 105), and the positive predictive value 99% (86 of 87). Nondiagnostic cutting needle biopsy (n = 16) was not related to the age of the patient, experience of the radiologist, number of needle insertions, or site of puncture. No patient exhibited tumor growth along the needle tract. Complications occurred in 10 cases (7%) and pain in 20 (14%). CONCLUSION: Cutting needle biopsy is an accurate and safe procedure with a low learning threshold that is recommended for diagnosing malignancies in childhood.
