ABSTRACT
Multiple defects in apoptotic pathways have been described in peripheral neuroblastic tumours (NTs). Mitosis-karyorrhexis index (MKI) is a reliable morphological marker identifying favourable and unfavourable NTs. The extent to which apoptotic processes contribute to determine the clinical significance of MKI is still undefined. Apoptosis was investigated in a series of 110 peripheral NTs by comparing MKI to immunohistochemical and molecular apoptotic features. High MKI was found in 55 out of 110 NTs (50%) and was associated with advanced stage (P = 0.007), neuroblastoma (NB) histological category (P = 0.024), MYCN amplification (P < 0.001), and poor outcome (P = 0.011). Overall survival probability was 45% in patients with high MKI compared to 73% in patients with low MKI. In the same 110 NTs, the expression of Bcl-2, Bcl-XL, Bax and Mcl-1 was studied by immunohistochemistry, but no significant associations were found with clinicohistological features. Microarray analysis of apoptotic genes was performed in 40 out of 110 representative tumours. No significant association was found between the expression of apoptotic genes and MKI or clinicohistological features. Proliferative activity was assessed in 60 out of 110 representative tumours using Ki67 immunostaining, but no significant correlations with MKI or clinicobiological features were found. In NTs, the combination of apoptosis and proliferation as expressed by MKI is a significant prognostic parameter, although neither of them is per se indicative of the clinicobiological behaviour and outcome.
Subject(s)
Apoptosis , Neuroblastoma/diagnosis , Neuroblastoma/metabolism , Peripheral Nervous System Neoplasms/diagnosis , Peripheral Nervous System Neoplasms/metabolism , Adolescent , Biomarkers, Tumor/biosynthesis , Cell Proliferation , Child , Child, Preschool , Female , Gene Expression Profiling , Humans , Infant , Infant, Newborn , Male , Mitotic Index , Neuroblastoma/genetics , Oligonucleotide Array Sequence Analysis , Peripheral Nervous System Neoplasms/genetics , Predictive Value of Tests , Prognosis , Survival AnalysisSubject(s)
Hydrocarbons/adverse effects , Pneumonia, Aspiration/chemically induced , Pneumonia, Lipid/chemically induced , Biopsy , Child , Chromatography, Gas , Humans , Hydrocarbons/analysis , Lung/analysis , Lung/pathology , Lung/ultrastructure , Male , Pneumonia, Lipid/diagnostic imaging , Pneumonia, Lipid/pathology , Tomography, X-Ray ComputedSubject(s)
Celiac Disease/diet therapy , Intestinal Mucosa/metabolism , Motilin/analysis , Adolescent , Biopsy , Celiac Disease/metabolism , Celiac Disease/pathology , Child , Child, Preschool , Female , Glutens , Humans , Immunoenzyme Techniques , Infant , Intestinal Mucosa/pathology , Jejunum/metabolism , Jejunum/pathology , MaleABSTRACT
The results of an immunocytochemical evaluation of tyrosine hydroxylase (TH) immunoreactivity in 30 neuroblastic tumors of infancy are reported. Although no correlations could be found between the immunoreactive pattern and the site of origin or the staging of the tumor, a positive relationship between the urinary catecholamine output and the density of TH-immunoreactive cells could be established. TH was mostly localized on the cytoplasm of the differentiating neuroblasts, whereas immature elements were rarely positive. Moreover, 2 stage IVS cases did not contain any TH immunoreactivity. The possible significance of this finding in the investigation of this form of neuroblastoma, which has a peculiar biological behavior, is considered.
