Clinical significance of vanillylmandelic acid in neuroblastoma
Keywords:Homovanillic acid, Lactate dehydrogenase, Metaiodobenzylguanidine, Neuroblastoma, Neuron-specific enolase, Vanillylmandelic acid
Background: The second most common solid tumor in children is Neuroblastoma (NB). In about 90% of cases of NB, elevated levels of catecholamines or its metabolites are found in the urine or blood which includes Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA). Ferritin, Neuron-Specific Enolase (NSE) and Lactate Dehydrogenase (LDH) are commonly assessed in children suspected to have NB, and the levels of these markers are commonly used for differential diagnosis. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123(123I) Metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. To evaluate the utility of these marker present study was undertaken with 91 NB patients and 40 normal healthy control.
Methods: The study comprised of blood samples and 24 hour’s urine sample from 40 normal healthy subjects and 91 untreated patients with histologically proven Stage III and IV NB cases referred to our institute. Method used for NSE was Enzyme Immunoassay (Elisa), serum Ferritin was MIA, LDH-photometry and VMA by Column Chromatography.
Results: Amongst the parameters studied VMA showed highest sensitivity (91%), specificity (94.4%) positive predictive value (97.8%) and 85% negative predictive value at the cut off levels of 7mg/ ml of creatinine as compared to other studied parameters.
Conclusions: This study suggests that the detection of VMA in combination with routine histological examination, MIBG scan, serum NSE and LDH may improve the diagnosis of Neuroblastoma.
Chauvin F, Mathieu P, Frappaz D, Lasset C, Favrot MC, Greffe J, et al. Screening for neuroblastoma in France: methodological aspects and preliminary observations. Medical and Pediatric Oncology: The Official J SIOP-Intern Soc Pediatr Oncol (Societé Internationale d'Oncologie Pédiatrique. 1997;28(2):81-91.
Sharp SE, Trout AT, Weiss BD, Gelfand MJ. MIBG in neuroblastoma diagnostic imaging and therapy. Radiographics. 2016;36(1):258-78.
Vallabhajosula S, Nikolopoulou A. Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology. Seminars Nuclear Med. 2011;41(5):324-33.
Wieland DM, Wu JL, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with iodobenzylguanidine. J Nuclear Med. 1980;21(4):349-53.
Strenger V, Kerbl R, Dornbusch HJ, Ladenstein R, Ambros PF, Ambros IM, et al. Diagnostic and prognostic impact of urinary catecholamines in neuroblastoma patients. Pediatr Blood Cancer. 2007;48(5):504-9.
Maris JM. Recent advances in neuroblastoma. N Engl J Med.; 2010׃362(23):2202-11.
Berthold F, Hunneman DH, Harms D, Käser H, Zieschang J. Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. Europ J Cancer. 1992;28(12):1950-4.
Lamberts SW, Hofland LJ, Nobels FR. Neuroendocrine tumor markers. Front Neuroendocrinol; 2001;22:309-39.
Berthold F, Trechow R, Utsch S, Zieschang J. Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases. Am J Pediatr hematol/oncol. 1992;14(3):207-15.
Imashuku S, Yamanaka H, Morioka Y, Todo S. Serum ferritin in stage IV neuroblastoma. Am J pediatr hematol/oncol. 1988;10(1):39-41.
Children cancer survival rate 2019; available at www.hindustantimes.com/mumbai-news/children-s-cancer-survival-rate-20-in-india-80-in-the-west-say-mumbai-hospital-doctors. Accessed 1 June 2019.
Arora RS, Eden TO, Kapoor G. Epidemiology of childhood cancer in India. Ind J cancer. 2009;46(4):264.
Stiller C ed. Childhood cancer in Britain: Incidence survival, mortality. Oxford;Oxford University Press; 2007.
Gurney JG, Bondy ML. Epidemiology of childhood cancer. Principles Pract Pediatr Oncol. 2006;5:1-3.
Yeole BB. Role of the cancer registries in determining cancer mortality in Asia?. Asian Paci J Cancer Prevent. 2006;7(3):489.
Schleiermacher G, Rubie H, Hartmann O, Bergeron C, Chastagner P, Mechinaud F, et al. Treatment of stage 4s neuroblastoma–report of 10 years' experience of the French Society of Paediatric Oncology (SFOP). British J Cancer. 2003;89(3):470.
Hann HW, Levy HM, Evans AE. Serum ferritin as a guide to therapy in neuroblastoma. Cancer Res. 1980;40(5):1411-3.
Pang QM, Li K, Ma LJ, Sun RP. Clinical research on neuroblastoma based on serum lactate dehydrogenase. J Biol Regul Homeo Agents. 2015;29(1):131-4.
A study “Neuroblastoma workup” conducted by Byron D Joyner, MD, MPA; Chief Editor: Brian H Kopell, MD in July 2017 Available at: https://emedicine.medscape.com/article/439263-workup. Accessed 12 July 2017.
Smith SJ, Diehl NN, Smith BD, Mohney BG. Urine catecholamine levels as diagnostic markers for neuroblastoma in a defined population: implications for ophthalmic practice. Eye. 2010 Dec;24(12):1792-76.