title: Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinoma.
abstract: Malignant transformation of parathyroid tumours is rare. Nevertheless, this small subset of malignant tumours often creates diagnostic and therapeutic problems. In this work, the morphological characteristics of 26 primary parathyroid carcinomas and seven metastases have been studied. Furthermore, immunohistochemical expression profiles for the calcium sensing receptor (CASR), cyclin D1 (CCND1), and Ki-67 were determined for parathyroid carcinomas and compared with adenomas and hyperplasias using a tissue microarray. Loss of heterozygosity (LOH) of the chromosome 1q region containing the HRPT2 gene and chromosome 11q (MEN1) was determined in the carcinomas. In contrast to the adenomas and hyperplasias, 31% of carcinomas demonstrated down-regulation of CASR. A significant correlation was found between CASR expression and the Ki-67 proliferation index. Chromosome 1q and chromosome 11q LOH were found in 12 of 22 (55%) and 11 of 22 (50%) carcinomas tested, respectively. Combined 1q and 11q LOH was seen in 8 of 22 (36%) carcinomas, in contrast to the low percentage of LOH reported in both regions in adenomas. In conclusion, this study demonstrates that combined 1q and 11q LOH in parathyroid tumours is suggestive of malignant behaviour. Strong down-regulation of the CASR protein is seen in a proportion of parathyroid carcinomas with a high proliferation index.
authors.affiliation: Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Carola J
authors.initials: CJ
authors.lastname: Haven
authors.forename: Marjo
authors.initials: M
authors.lastname: van Puijenbroek
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019938:Cyclin D1 / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D019656:Loss of Heterozygosity / Q000235:genetics; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010280:Parathyroid Glands / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D044169:Receptors, Calcium-Sensing / Q000032:analysis*
chemical_list: D019394:Ki-67 Antigen; D044169:Receptors, Calcium-Sensing; D019938:Cyclin D1