Loss of heterozygosity of selected tumor suppressor genes in parathyroid carcinoma.
BACKGROUND
The histologic diagnosis of parathyroid carcinoma (PC) is challenging. We evaluated a large PC series for loss of heterozygosity (LOH) of selected tumor suppressor genes with histopathologic correlation.


METHODS
Among 2,238 patients explored for primary hyperparathyroidism (PHP), the cytoarchitectural parameters of 60 patients with surgical and/or pathologic suspicion for PC were examined by 1 pathologist. PC was diagnosed with >/=1 of the following: extracapsular, thyroidal, perineural, or angiolymphatic invasion; atypical mitoses; or metastasis. LOH was determined for PC or parathyroid adenoma (PA) using a panel of 12 tumor suppressor gene loci. Fractional allelic loss (FAL) was calculated as the percentage of loci with LOH divided by the number of informative loci.


RESULTS
PC occurred in 0.8% of patients with PHP. Angiolymphatic (68%) and soft tissue (47%) invasion were the most common histologic findings. For PC, mean FAL was 32% vs 14% for PA (P = .03). Among informative cases, LOH was found at the HRPT2 locus in 7 of 14 (50%) PC vs 0 of 7 (0%) PA; the Rb locus in 4 of 15 (27%) PC vs 0 of 8 (0%) PA; the MEN1 locus in 6 of 15 (40%) PC vs 1 of 8 (13%) PA; and the 1p35.2-36.2 (including p21) locus in 8 of 13 (62%) PC vs 2 of 6 (33%) PA.


CONCLUSIONS
In PC diagnosed by strict histologic criteria, LOH for a selected tumor suppressor gene panel was common. Specific tumor suppressor genes such as HRPT2 demonstrated LOH in up to 50% of PC, while not seen in any PA. Evaluation of LOH may be useful for the definitive diagnosis of PC.
Yip
Linwah
L
Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Seethala
Raja R
RR
Nikiforova
Marina N
MN
Nikiforov
Yuri E
YE
Ogilvie
Jennifer B
JB
Carty
Sally E
SE
Yim
John H
JH
D016147:Genes, Tumor Suppressor; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000601:surgery*; D019656:Loss of Heterozygosity; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics
C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins