High-resolution molecular cytogenetic analysis of Wilms tumors highlights diagnostic difficulties among small round cell kidney tumors.

Many solid tumors exhibit characteristic gene fusions, which are reflected by balanced translocations at the cytogenetic level. These changes might be useful diagnostic and prognostic tools. In Wilms tumor (WT, nephroblastoma) no fusions genes or recurrent balanced translocations have been described thus far. To screen for cryptic balanced translocations, we have analyzed 17 renal neoplasms, histopathologically classified as WT, by a combination of G-banding, multicolor FISH, and subtelomeric FISH. This approach revealed several submicroscopic chromosomal aberrations and three different seemingly balanced translocations, resulting in a heterozygous deletion of HACE1, an EWSR1/ERG fusion, and an EWSR1/FLI1 fusion, respectively. As EWSR1 rearrangements are known to be a characteristic of Ewing tumors (ET), our findings illustrate the diagnostic problems regarding small cell kidney tumors and strongly argue for the need of adjuvant diagnostic techniques in this group of neoplasms. In summary, our genomic screening approach proved efficient in finding structural chromosomal aberrations. The fact that no recurrent translocations were found in the WTs of this study argues against the presence of a frequent pathognomonic translocation in this disease entity.

Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors.

PURPOSE: In many childhood neoplasms, prognostic subgroups have been defined based on specific chromosome changes. In Wilms' tumor (WT), such subclassification has been hampered by the diverse and relatively unspecific pattern of chromosomal imbalances present in these tumors. Unspecific patterns of cytogenetic imbalances in tumors are often caused by mitotic segregation errors due to short dysfunctional telomeres. As an alternative to cytogenetic classification, we therefore have evaluated whether the rate of telomere-dependent chromosomal instability could influence the clinical course in WT patients. EXPERIMENTAL DESIGN: Telomere function and mitotic segregation errors were assessed in 12 cultured tumors and in tumor tissue sections from 41 WT patients. RESULTS: Abnormal telomere shortening was found in cultured cells and in tissue sections from highly aggressive tumors. In vitro, dysfunctional telomeres were associated to specific cell division abnormalities, including anaphase bridges and multipolar mitoses. Assessment of mitotic figures in tissue sections revealed that anaphase bridges and multipolar mitoses were predominantly, but not exclusively, present in high-risk tumors and were predictors of poor event-free and overall survival. CONCLUSIONS: Telomere-dependent mitotic instability is present in a subgroup of WT, predominantly consisting of high-risk tumors.

Cytogenetic findings in pediatric renal cell carcinoma.

Adenocarcinomas of the kidney are rare childhood tumors. Only 30 cases with chromosomal abnormalities have been reported, and neither their karyotypic characteristics nor the molecular mechanisms behind their pathogenesis are clear, except for a special group of papillary tumors characterized by X-chromosome abnormalities. We have cytogenetically analyzed short-term cultured cells from two pediatric renal carcinomas, one papillary, and one chromophobe renal cell carcinoma, revealing the following karyotypes: 58-60,XX,-X,-1,+7,-8,-9,-11,-14,-15,+17,-18,-19,-21,-22 and 36,X,-X,-1,-2,-5,-6,-9,-10,-13,-17,-21/37,idem,+r/36,idem,-14,+1-2r, respectively. The findings indicate that subsets of pediatric renal cell carcinoma show karyotypes that are similar to their adult counterparts.

Nitric Oxide Synthase in Human Parathyroid Glands and Parathyroid Adenomas.

Nitric oxide (NO) is a novel gaseous intercellular transmitter thought to play important physiological roles in the regulation of blood flow and hormone secretion in, for example, the pituitary, the thyroid, and the endocrine pancreas. Whether nitric oxide synthase (NOS) is present in the human parathyroid glands has not yet been demonstrated. In the present study, histologically normal, but functionally suppressed human parathyroid glands and parathyroid adenomas from patients with primary hyperparathyroidism were investigated by immunocytochemistry with antibodies against neuronal NOS and by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. We also used H&E to identify the NOS-immunoreactive cells. Immunocytochemistry demonstrated the presence of neuronal-type NOS in a subpopulation of glandular cells, identified as oxyphilic cells, in both normal parathyroid glands and adenomas. NADPH-diaphorase staining visualized NOS in the endothelium of blood vessels and in glandular cells, corresponding to those containing immunoreactive NOS. In addition, we found NADPIH-diaphorase staining in many chief cells. Our results indicate that both glandular cells and vascular endothelium in human parathyroid glands and adenomas express NOS. There is thus a morphological substrate for locally produced NO that may be involved in the regulation of parathyroid blood flow and hormone secretion.