title: Dysregulation of the cell cycle and chromosomal imbalances in juxtaglomerular cell tumors - a comparative study with endocrine tumors of the pancreas.
abstract: Two juxtaglomerular cell tumors (JGCTs) were investigated in comparison with 14 endocrine tumors of the pancreas (ETPs), focusing on the cell cycle, apoptosis, and cytogenetic changes. JGCTs revealed nuclear accumulation of Cyclin D(1), together with the cyclin-dependent kinase inhibitors p21(Cip1/Waf1) and p27(Kip1). In contrast, no accumulation of Cyclin D(3), p53, p16(INK4a), or Mdm-2 was seen. Bcl-2 protein was intensively, but Rb only moderately, expressed. This immunoreactive profile was not found in the ETPs, which were negative for Bcl-2, p27(Kip1), p21(Cip1/Waf1), and - with one exception - for Cyclin D(1) (1/14) but expressed Cyclin D(3) in 7/14 cases. JGCTs displayed characteristic genetic alterations with combined losses of chromosomes 9, 11, 15, and 21 and gains of chromosome 18. In contrast, no characteristic pattern of genetic alterations was found in ETPs. In both, the amount of chromosomal aberrations correlated with tumor size. In small ETPs and JGCTs, genetic losses dominated over gains of chromosomes, whereas in large/malignant ETPs, gains and losses were equally affected. Thus, JGCTs represent a special type of renal endocrine neoplasm characterized by deregulation of cell cycle components and a typical profile of chromosomal aberrations. Since only two JCTs were investigated, further studies for validation of these results are, however, necessary.
authors.affiliation: Pathologisches Institut der Ludwig-Maximilians-Universität München, Thalkirchner Strasse 36, 80337 München, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Assmann
authors.forename: Irmgard
authors.initials: I
authors.lastname: Verdorfer
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Markus
authors.initials: M
authors.lastname: Bader
authors.forename: Josef
authors.initials: J
authors.lastname: Müller-Höcker
mesh_terms: D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis*; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007606:Juxtaglomerular Apparatus / Q000737:chemistry / Q000473:pathology; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D047368:Tumor Burden
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins