ABSTRACT
Several podocyte-related markers are organized to express in glomerular differentiation. However, whether expression of them is virtually synchronized and a reliable indicator of the state of differentiation is unknown. The present study investigated, by immunohistochemistry, the divergent expression of several podocyte markers in the improperly differentiated glomeruloid bodies from four cases of Wilms tumors. The glomeruloid bodies were classified into immature (IGB) or mature forms (MGB) based on morphology and epithelial features. Podocytes in IGB expressed WT1, synaptopodin, podocalyxin, and nephrin, and their expression was stronger in MGB. In contrast, Pax2 was strong in IGB and diminished in MGB. p27 was first expressed in MGB. The expression pattern in each molecule mimics normal glomerulogenesis. Podocytes in MGB showed persistent expression of bcl-2 and cytokeratin with synaptopodin, podocalyxin, and nephrin by serial section, a finding unusual for normal glomerulogenesis. Moreover, parietal cells in MGB also occasionally expressed these podocyte markers. The ultrastructure revealed that podocytes in MGB showed tight junctions without foot process formations, which indicated incomplete differentiation. These results suggest that a set of podocyte differentiation markers are occasionally diversely expressed, and raise the possibility that expression of these markers is insufficient to determine the state of terminal differentiation in podocytes.
Subject(s)
Biomarkers, Tumor/metabolism , Kidney Glomerulus/metabolism , Kidney Neoplasms/metabolism , Muscle Proteins , Wilms Tumor/metabolism , Female , Humans , Infant , Keratins/metabolism , Kidney Glomerulus/pathology , Kidney Glomerulus/ultrastructure , Kidney Neoplasms/pathology , Male , Membrane Proteins , Microfilament Proteins/metabolism , Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Sialoglycoproteins/metabolism , Tight Junctions/ultrastructure , WT1 Proteins/metabolism , Wilms Tumor/pathologyABSTRACT
Neuroblastoma (NB), one of the most common solid tumors among children, is histologically classified by the degree of maturation. To elucidate the mechanisms underlying its maturational sequence, we analyzed gene-expression profiles of 14 NB tumors on cDNA microarrays consisting of 23,040 genes. Computational analysis identified 78 genes whose expression levels were significantly different between differentiating NB tumors and poorly differentiated NB tumors. This group included genes associated with cell maturation and apoptosis. Among them we identified 15 that were up-regulated in Stage IV NB tumors; these included genes encoding cell adhesion molecules and cytoskeleton proteins. The set of genes we report here should contribute to a better understanding of NB tumor maturation and could lead to development of new therapeutic strategies.
