Parathyroid (PT) carcinoma is an uncommon cause of PTH-dependent hypercalcemia. It is infrequent in primary hyperparathyroidism (HPT) and rarely associated with secundary uremic HPT. A spontaneously growing permanent cell line (Kich-1) was established from an enlarged PT gland of a patient with secondary HPT. The cells exhibit increased proliferative capacity and are immunoreactive for cytokeratins 8,18 and 19 (12%), EMA (25%), vimentin (36%), CD68 (95%), and S100 (5%), while Chromogranin A and Synaptophysin were not detected. The high levels of PTH (1-84) i.e 546pg/mg of DNA detected in the primary culture declined during the passages and remained at low levels (between 9 and 11 pg/mg of DNA). By RT-PCR analysis, an aberrant band of 260 bp PTH gene transcript and normal Ca-sensing receptor (CaSR) mRNA (285bp) were identified in Kich-1 cells. Cytogenetic analysis (RHG-banding) revealed one predominant line with hypo-triploid karyotype with a chromosome number ranging between 43 and 72. Two larger size marker chromosomes in addition to a cluster of double minute chromosomes as well as endomitotic figures were observed in 15% of the metaphases. Comparative Genomic Hyridization (CGH) on human metaphases confirmed DNA gains on chromosomes 1q, 5q, 9q, the entire chromosome 11 and on 22q, while DNA losses were detected on 1p, 5p, 6p, 18q and chromosome 19. FISH analysis with single locus probes for c-Myc and Cyclin D1 proto-oncogenes revealed and increased number of hybridization clusters ranging between 6 -26 and 4-18 gene copies respectively. The analysis of 19 metaphases hybridized with painting probe for the entire chromosomes 8 and 11, showed translocated sequences of these chromosomes on other marker chromosomes suggesting an inter-chromosomal amplification. In conclusion, the PT carcinoma derived Kich-1 cell line stably expressed morphological features of neoplastic PT cells. It could be an useful model for multidciplinary studies with respect to PT morphology, parathyroid cell differentiation and regulatory pathways for PTH secretion.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5265.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO