Prognostic significance of MYCN amplification in children neuroblastic tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT.</p><p><b>METHODS</b>The clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed.</p><p><b>RESULTS</b>The study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05).</p><p><b>CONCLUSIONS</b>NT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.</p>

Matrine inhibits the proliferation of neuroblastoma LA-N-5 cell and MYCN mRNA expression / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Neuroblastoma is the most common malignant solid tumor in children under 4 years. Amplification of MYCN oncogene is associated with advanced-stage disease, rapid tumor progression, resistance to treatment, and poor outcome. Matirne has the anti-tumor activity. This study was designed to investigate the effects of matrine on LA-N-5 cell line proliferation and MYCN gene mRNA expression.</p><p><b>METHODS</b>Neuroblastoma LA-N-5 cells were treated by 0.25, 0.50, 0.75 or 1.00 mg/mL matrine. MTT was used to measure the levels of the proliferation of LA-N-5 cells cultured with different concentrations of matrine. MYCN gene mRNA expression in LA-N-5 cells was measured using real time RT-PCR with SYBR GREEN I fluorescence.</p><p><b>RESULTS</b>The proliferation of LA-N-5 cells was obviously inhibited by matrine in a dose- and time- dependent manner. Matrine of 1.00 mg/mL treatment for 72 hrs produced a best effect, with an inhibitory rate of LA-N-5 cell proliferation of 36.3% and an inhibitory rate of MYCN gene mRNA expression of 44.6%.</p><p><b>CONCLUSIONS</b>Matrine may inhibit the growth of neuroblastoma cells and down-regulate MYCN mRNA expression. It may be promising as a new drug for treatment of neuroblastoma.</p>

Study on MYCN gene amplification and CD44 expression in neuroblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess the relationship between MYCN amplification in neuroblastoma (NB), tumor stage and prognosis; and to evaluate the usefulness of CD44 in predicting prognosis of NB.</p><p><b>METHODS</b>Differential polymerase chain reaction (D-PCR) with serial dilution assay was used to quantify the MYCN gene copy number in 33 paraffin-embedded tissue samples of NB. All the samples were also studied by immunohistochemistry for CD44. The results were correlated with various prognostic factors of NB, including patient age, tumor stage, pathologic type and MYCN gene amplification.</p><p><b>RESULTS</b>MYCN amplification was identified in 10 of the 33 samples studied (30.3%), which all were in high clinical stage (stage III or IV) and occurred in patients older than 1 year of age. MYCN amplification also significantly correlated with poor clinical outcome (P < 0.01). CD44 was positive in 21 cases and often occurred in patients below 1 year of age, in low clinical stage, with favorable histology and without MYCN gene amplification. The two-year survival rate of CD44-positive group (57.1%) was higher than that of CD44-negative group (8.3%, P < 0.01). Stronger CD44 expression was also associated with better prognosis (P < 0.01).</p><p><b>CONCLUSIONS</b>MYCN gene amplification is significantly associated with advanced tumor stage and poor prognosis in patients with NB. CD44 expression is a reliable marker for better prognosis and is complementary to MYCN amplification assay. D-PCR with serial dilution assay is also suitable for clinical use in quantifying MYCN copy number in NB.</p>