Differential expression of kinase genes in primary hyperparathyroidism: adenoma versus normal and hyperplastic parathyroid tissue.
BACKGROUND
Differentiation between adenoma and hyperplasia or even normal parathyroid tissue is difficult and based mainly on the surgeon's skill. Exploration of genes that express differentially in these various tissues using microarrays and other sophisticated research tools will enable identification and perhaps development of new methods of perioperative diagnosis.


OBJECTIVE
To assemble a panel of kinase genes to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue.


METHODS
RNA was extracted from adenoma, hyperplasia, and normal parathyroid tissue and hybridized to a microarray containing 359 human cDNAs of known kinase genes. Signals of exposure were scanned and quantified with software for digital image analysis. Semiquantitative reverse transcriptase polymerase chain reaction analysis of sample genes was performed, up-regulated or down-regulated, to validate the microarray results.


RESULTS
The ratio values considered significant (<0.5 or >1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for blood vessel angiogenesis and genes belonging to the cyclin-dependent kinase inhibitor groups. Genes down-regulated in parathyroid adenoma are related to cellular growth and apoptosis--genes from the mitogen-activated protein kinase group and DNA-dependent protein kinase group. An interesting gene down-regulated in the parathyroid adenoma samples is related to the serine/threonine protein kinases that exert a key function in calcium handling. A panel of 5 genes was defined: p19, p21 and the gene for vascular endothelial growth factor from the up-regulated group, and the gene for protein kinase C and SGK from the down-regulated group. Reverse transcriptase polymerase chain reaction confirmed the microarray results for these genes.


CONCLUSIONS
The kinase genes panel presented can be used to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue in particular when histopathology fails to provide a decisive diagnosis.
Schachter
Pinhas P
PP
Department of Surgery A, E. Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. pini_sc@yahoo.com
Ayesh
Suhail
S
Matouk
Imad
I
Schneider
Tamar
T
Czerniak
Abraham
A
Hochberg
Abraham
A
D000236:Adenoma / Q000175:diagnosis / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010282:Parathyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010770:Phosphotransferases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010770:Phosphotransferases