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

Abstract

Abstract. 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 ß (THRß) 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.

The Hypothalamic–Pituitary–Thyroid Axis Equivalent in Normal and Cancerous Oral Tissues: A Scoping Review

“…A basic overview of parameters of these eligible publications is discussed here. Study characteristics of the 14 studies [18][19][20][21][22][23][24][25][26][27][28][29][30][31], including the type of study, population, intervention, control, outcomes (PICO), biomarkers, assay methodology, and specimen types, are presented in Table 1. The final 14 studies were then eligible for inclusion in this scoping review.…”

“…With these studies, techniques used could potentially produce confounding results through contamination of healthy cells in carcinoma samples and the number of PCR cycles, with more cycles increasing the chance of homodimers forming heterodimers [19]. Reaction failure [25] and samples being "not done" [26] were also reported.…”

“…Loss of heterozygosity involving the THRB gene loci in human samples was reported in four studies [19,25,26,29] summarized in Table 2. El-Naggar et al [19] reported that three of nine informative primary head and neck squamous carcinoma specimens exhibited LOH at the THRB locus, with all three of these carcinomas showing DNA aneuploidy.…”

“…El-Naggar et al [19] reported that three of nine informative primary head and neck squamous carcinoma specimens exhibited LOH at the THRB locus, with all three of these carcinomas showing DNA aneuploidy. Miyashita et al [25] reported two of seven informative OSCC tissue samples exhibiting LOH on 3p24.1-22 (THRB) loci. Patridge et al [26] found that 10 of 36 informative primary OSCC samples exhibited LOH at the 3p24-26 chromosomal region (which includes THRB loci).…”

Role of Hormones in Oral Squamous Cell Carcinoma - An Update

“…Coexpression of PTHrP and parathyroid hormone-related protein type 1 receptor (PTHR1) is considered to be a poor predictor of patient survival. Loss of heterozygosity (LOH) and microsatellite instability (MSI) in PTHR1 may be involved in oral carcinogenesis [51].…”