Loss of heterozygosity of the PTH/PTHrP type 1 receptor in oral squamous cell carcinoma.

Parathyroid hormone-related protein (PTHrP) is produced by various types of carcinomas, and is an important factor in the development of bone metastasis. The coexpression of PTHrP and parathyroid hormone/parathyroid hormone-related protein type 1 receptor (PTHR1) in cancer predicts poor patient survival. While genetic transformations of thyroid hormone receptor β (THRβ) have been reported as being associated with reduced survival in patients with oral squamous cell carcinoma (OSCC), the details of transformations in PTHR1 have not been extensively analyzed. The aim of this study was to examine loss of heterozygosity (LOH) and microsatellite instability (MSI) in PTHR1 in OSCC. Analysis of genetic transformations using microdissected clinical tissues revealed that the proportions of LOH and MSI in PTHR1 were 30.0 (3/10) and 20.0% (2/10), respectively. Furthermore, the proportion of carcinomas which developed with LOH on the chromosome of PTHR1 and without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCA1, BRCA2 and DCC was 20.0% (2/10). These observations suggest that transformations in PTHR1 may be involved in carcinogenesis in human OSCC.