Identification of Novel Prognostic Markers in Relapsing Localized Resectable Neuroblastoma

Abstract

Patients with localized resectable neuroblastoma (NB) generally have an excellent prognosis and can be treated by surgery alone, but approximately 10% of them develop local recurrences or metastatic progression. The known predictive risk factors are important for the identification of localized resectable NB patients at risk of relapse and/or progression, who may benefit from early and aggressive treatment. These factors, however, identify only a subset of patients at risk, and the search for novel prognostic markers is warranted. This review focuses on the recent advances in the identification of new prognostic markers. Recently we addressed the search of novel genetic prognostic markers in a selected cohort of patients with stroma-poor localized resectable NB who underwent disease relapse or progression (group 1) or complete remission (group 2). High-resolution array-comparative genomic hybridization (CGH) DNA copy-number analysis technology was used. Chromosome 1p36.22p36.32 loss and 1q22qter gain, detected almost exclusively in group 1 patients, were significantly associated with poor event-free survival (EFS). Increasing evidence points to anaplastic lymphoma kinase (ALK) as a fundamental oncogene associated with NB. The immunohistochemical analysis of sporadic NB localized resectable primary tumors (stage 1-2) showed a correlation between aberrant ALK level of expression and tumor progression and clinical outcome. Moreover, other factors that might influence the clinical behavior of these tumors will be reviewed.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive markers in hepatoblastoma

“…The PRETEXT system, a preoperative surgical staging system, which was based on the anatomy of the liver, was a relatively objective diagnostic method to assess the extent of the tumor ( 32 , 33 ). LDH is a sensitive indicator of tumor burden and metabolic status in vivo , and its increase can indirectly reflect the size of tumor volume and metabolic activity in patients, often indicating that children are in advanced stage and have poor prognosis ( 34 ). Moon et al showed that the survival of patients with HB is usually correlated with the PRETEXT classification ( 35 ).…”

Aspectos Clínicos, Epidemiológicos E Sobrevida De Crianças Com Neuroblastoma: 21 Anos De Experiência Do Instituto De Oncologia Pediátrica, São Paulo

“…The MYCN oncogene is an important prognostic factor in NB, as it is associated with aggressive behavior and an unfavorable outcome. 2 , 4 It is amplified in 25 to 35% of the NBs, and in about 30 to 40% of the cases dealing with stage 3 and 4 patients. 1 , 14 , 28 In our study, MYCN oncogene amplification was performed in 44 (17%) patients, and 10 (25%) presented MYCN amplification, of which 90% had an advanced disease at the time of diagnosis (stages 3 and 4).…”

“…Factors associated with a worse prognosis include age greater than 1 year old, a metastatic disease at the time diagnosis and an unfavorable histopathological classification, according to Shimada’s classification. 2 The patient’s age is an independent prognostic factor. Patients younger than 1 year of age at the time of diagnosis present better odds of survival than older children.…”

“…Neuroblastoma (NB) is the most common malignant extracranial solid tumor found in children, and it is the most common cancer to be diagnosed in the first year of a child’s life. 1 , 2 , 3 , 4 , 5 , 6 The annual incidence of the disease is 10.5 per one million children under the age of 15, and there around 700 new cases per year in the United States. 1 , 2 , 4 , 5 , 7 In Brazil, from a study based on an analysis of the population records for cancer, which included 12 cities and the Federal District, the incidence of NB was 5.9 per one million inhabitants under the age of 15.…”

Recurrent Neuroblastoma

“…Furthermore, high ALK protein expression, though uncommon, may be prognostic in Stage 1 and 2 patients. Six of eight Stage 1 and 2 patients with high wild-type ALK expression experience relapse (Parodi et al, 2011). Furthermore, MYCN amplification, and lumbar puncture at diagnosis were found to be significant risk factors for CNS recurrences in a report of 434 Stage 4 NB patients (Matthay et al, 2003a).…”