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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Catherine Madorin; Randall P Owen; William D Fraser; Phillip K Pellitteri; Brian Radbill; Alessandra Rinaldo; Raja R Seethala; Ashok R Shaha; Carl E Silver; Matthew Y Suh; Barrie Weinstein; Alfio Ferlito Journal: Eur Arch Otorhinolaryngol Date: 2011-11-20 Impact factor: 2.503