Predicting outcome of Neuroblastoma using MYCN status and Trk-A expression

Gopinath, V (2012) Predicting outcome of Neuroblastoma using MYCN status and Trk-A expression. Masters thesis, Madras Medical College, Chennai.


Download (3MB) | Preview


INTRODUCTION: The term neuroblastoma was introduced in 1910 by Wright when he demonstrated that the tumor originated from embryonal neuroblasts of the sympathetic peripheral nervous system (Wright 1910). The ability of neuroblastoma for spontaneous maturation into ganglioneuroma was first described in 1927 by Cushing and Wolbach. Vanillylmandelic acid (VMA) was identified as one of the main metabolites and tumor markers. In 1971 Evans et al. proposed the first internationally accepted staging system. Schwab and coworkers (1983) detected MYCN amplification as an important molecular feature of cell lines and primary tumors which proved to be a reliable marker for indicating rapid tumor progression. Neuroblastoma is the third most common pediatric cancer. It is the most common extracranial solid tumor of childhood and the most common malignancy among infants.India belong to low incidence group. Neuroblastoma is an embryonal cancer of the postganglionic sympathetic nervous system, most commonly arises in the adrenal gland. The clinical hallmark of neuroblastoma is that it can regress spontaneously or progress to an end stage disease. AIMS OF THE STUDY: 1. To determine the MYCN amplification in tissue samples of Neuroblastoma cases. 2. To determine the Trk - A expression in tissue samples of Neuroblastoma cases. 3. To correlate clinical status,stage and histopathology of the disease with the prognostic markers (MYCN & Trk-A). MATERIALS & METHODS: This study on neuroblastoma in children is based on patients admitted to the Institute of Child Health and hospital for children [ICH & HC], Egmore during the period from June 2011 to March 2012. The study includes boys and girls between the age group 8 months to 12 years. Design of the study: A prospective, collaborative clinical and molecular study. Subject Selection: New cases of neuroblastoma. Inclusion Criteria: New cases of neuroblastoma who have never received chemotherapy before. Exclusion Criteria: Cases of neuroblastoma who are on chemotherapy or completed chemotherapy. Follow up: Assess tumour status by clinical examination, Complete blood count, Ultrasound & X rays/ CT. RESULTS: This study conducted at ICH & HC is a prospective pilot study done between June 2011 and March 2012 and it encompasses a total of 14 children who were diagnosed to have Neuroblastoma, of which 4 cases were not included in the study, of which 2 cases were diagnosed only based on Immunohistochemistry (Synaptophysin, S-100 positive) from bone marrow aspirate which showed small round cells and no tissue was available for genetic study. One of which had meningeal deposits and bone marrow positive, from which tissue sample could not be taken. In the other 2 cases, one was initially diagnosed as Rhabdomyosarcoma prostate and chemotherapy was started and the other case tissue sample was inadequate. In this study group total number of boys were 5 (50%) and the total number of girls were 5 (50%). The youngest age at presentation was 8 months and the oldest child was 12 years. Of the 10 children in the study the most common presenting symptom was mass in the abdomen (60%) noted by the parents. Abdominal distension was the next common complaint (20%). Nonspecific complaints like fever, loss of appetite and weight were noted in 2 cases (20%). CONCLUSION: Stage – 3 & 4 tumour exhibit poor prognosis. • Neuroblastoma cases with age more than 1 year showed poor prognosis. • N-myc amplification detection by polymerase chain reaction (Taq Man quantitative PCR) is rapid, accurate and sensitive. • The N-myc amplified tumors have been linked to more aggressive behavior, rapid tumor progression and poor prognosis. • N-myc amplification is seen more in patients older than 1 year, male and stage IV disease. • Trk A expression may be low in our population, but needs large sample to study and for accurate detection may need Real time PCR. • This study reinforces the importance of N-myc amplification on prognosis and tumor progression. • More accurate prognostic assessment of patients with neuroblastoma is required for the choice of risk-related therapy.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Predicting outcome, Neuroblastoma, MYCN status, Trk-A expression.
Subjects: MEDICAL > Paediatric Surgery
Depositing User: Subramani R
Date Deposited: 11 Sep 2020 16:11
Last Modified: 11 Sep 2020 16:11

Actions (login required)

View Item View Item