ABSTRACT
BACKGROUND: Neurotrophin-3 (NT-3), a member of the NT family, has only been considered an ancillary compound that provides anti-apoptotic benefits by inactivating tropomyosin receptor kinase C (TrkC)-induced apoptotic signals. However, little is known about the clinical relevance of NT-3 expression itself in neuroblastoma. The purpose of this study was to assess NT-3 expression in patients with neuroblastoma and its relevance to clinicopathologic findings and treatment outcomes. METHODS: In this study, expression of NT-3 and TrkC was analyzed using immunohistochemistry in 240 patients with newly diagnosed neuroblastoma. RESULTS: The results of the study revealed that NT-3 expression was associated with older age at diagnosis, localized tumors, and more differentiated tumors but was not associated with early treatment response (degree of residual tumor volume after three cycles of chemotherapy) and progression-free survival (PFS). However, when analysis was confined to patients with MYCN amplified tumors, NT-3 expression was associated with better early treatment response with borderline significance (P = 0.092) and higher PFS (86.9% vs. 58.2%; P = 0.044). In multivariate analysis in patients with MYCN amplified tumors, NT-3 was independent prognostic factor (hazard ratio, 0.246; 95% confidence interval, 0.061-0.997; P = 0.050). In another subgroup analysis, the early treatment response was better if NT-3 was expressed in patients without TrkC expression (P = 0.053) while it was poorer in patients with TrkC expression (P = 0.023). CONCLUSION: This study suggests that NT-3 expression in neuroblastoma has its own clinical significance independent of TrkC expression, and its prognostic significance differs depending on the status of MYCN amplification and/or TrkC expression.
Subject(s)
N-Myc Proto-Oncogene Protein/metabolism , Neuroblastoma/diagnosis , Neurotrophin 3/metabolism , Receptor, trkC/metabolism , Adolescent , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Infant , Infant, Newborn , Male , N-Myc Proto-Oncogene Protein/genetics , Neoplasm Staging , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Neurotrophin 3/genetics , Prognosis , Progression-Free Survival , Proportional Hazards Models , Real-Time Polymerase Chain Reaction , Receptor, trkC/geneticsABSTRACT
BACKGROUND: This study investigated the clinical significance of MYCN amplification within high-risk neuroblastoma (NB). METHODS: Medical records of 135 patients who were diagnosed with high-risk NB from 2004 to 2016 were reviewed. RESULTS: Fifty-one (38%) patients had MYCN amplified tumors, and the remaining 84 (62%) had nonamplified tumors. MYCN amplification was associated with abdominal primary site, less differentiated pathology, higher levels of lactate dehydrogenase and neuron-specific enolase (NSE), lower vanillylmandelic acid level, and larger primary tumor volume at diagnosis. MYCN amplification was associated with a better early response (faster reduction of primary tumor volume and NSE level). The proportion of patients in complete response or very good partial response after induction treatment was relatively higher in MYCN amplified tumors than in nonamplified tumors; however, all progressions during induction treatment occurred only in MYCN amplified tumors (P = 0.007). The time to progression was shorter (median 1.5 years vs. 1.9 years, P = 0.037) and survival after relapse/progression was worse in MYCN amplified tumors (3 year overall survival: 7.7 ± 7.4% vs. 20.5 ± 8.8%, P = 0.046). There was no difference in event-free survival and overall survival between MYCN amplified and nonamplified tumors. CONCLUSION: MYCN amplification was associated with more aggressive features at diagnosis and a better early response, but a higher progression rate during induction treatment and lower chance of survival after relapse/progression. There was no difference in survival rates according to MYCN amplification in patients with high-risk NB.
Subject(s)
N-Myc Proto-Oncogene Protein/genetics , Neuroblastoma/genetics , Neuroblastoma/pathology , Adolescent , Child , Child, Preschool , Female , Gene Amplification , Humans , Infant , Male , Neuroblastoma/mortality , Progression-Free Survival , Retrospective StudiesABSTRACT
Penicillium marneffei is the only dimorphic fungus among Penicillium spp. that can cause a fatal infection in immunocompromised patients. P. marneffei is endemic in Southeast Asia and eastern China. P. marneffei infection is an AIDS-defining illness and the third most common opportunistic infection in the endemic regions. Here, the authors report a case of disseminated P. marneffei infection in a patient who underwent liver transplantation in China. During the hospital stay, the mold form of the fungus that produced a red wine-colored pigment on the agar plate was isolated from the patient's urine, transtracheal aspirate, and blood. The fungus was identified as P. marneffei by direct sequencing of the D1-D2 and ITS regions. Thermal dimorphism was also confirmed by subculturing the colony at 37 degrees C. To the best of our knowledge, this is the first Korean case of disseminated P. marneffei infection in a liver transplant recipient.
