Microsatellite instability and loss of heterozygosity in primary and secondary proliferative lesions of the parathyroid gland

Clonality and genetic abnormalities were evaluated to characterize prolifer ative lesions of the parathyroid gland. Fourteen lesions from patients with single-gland proliferation (adenomas [PA]), 6 lesions from patients with m ultiple-gland proliferation (primary hyperparathyroidism [PHPT]), and 47 le sions from 16 patients with secondary hyperparathyroidism (SHPT) were exami ned. Based on the X chromatin inactivation pattern, which was revealed by a HUMARA assay of lesions from female patients (n = 34; 24 informative cases ), monoclonality was demonstrated in 6 of 10 PA (60%), 2 of 5 PHPT (40%), a nd 6 of 9 SHPT lesions (14 of 27 lesions, 52%). By PCR analysis using 17 mi crosatellite markers on eight chromosomes (chromosomes 1, 2, 3, 5, 6, 11, 1 3, and 17), loss of heterozygosity was sporadically observed in 4 of 14 PA, 3 of 6 PHPT, and 7 of 47 SHPT lesions, in most cases on a single locus of chromosome 11. On the other hand, microsateliite instability was observed m ore frequently: ie, in six PA, five PHPT, and nine SHPT lesions. The profil e of microsatellite instability depended on the type of proliferation: micr osatellite instability (MI) seemed to cluster in the region of chromosome 1 1 in PA. Microsatellite instability on TP53 was observed in 3 of 6 PHPT les ions and in 2 of 47 SHPT lesions but in no PA lesions. Microsatellite insta bility on Mfd47 was observed in only some cases of SHPT. Although no signif icant correlation was identified among histologic features, clonality, and genetic abnormalities in cases of primary proliferation, genetic abnormalit ies were more frequently observed in SHPT lesions that lacked fat tissues. Thus, genetic instability might be important in proliferative disorders of the parathyroid gland, either with or without uremia. However, genetic inst ability seems to be induced by different mechanisms in the three types of p roliferation studied. In SHPT, the absence of fat tissues may indicate that the proliferation is accompanied by genetic changes.