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.