Microsatellite instability and loss of heterozygosity in primary and secondary proliferative lesions of the parathyroid gland.
Clonality and genetic abnormalities were evaluated to characterize proliferative lesions of the parathyroid gland. Fourteen lesions from patients with single-gland proliferation (adenomas [PA]), 6 lesions from patients with multiple-gland proliferation (primary hyperparathyroidism [PHPT]), and 47 lesions from 16 patients with secondary hyperparathyroidism (SHPT) were examined. 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%), and 6 of 9 SHPT lesions (14 of 27 lesions, 52%). By PCR analysis using 17 microsatellite markers on eight chromosomes (chromosomes 1, 2, 3, 5, 6, 11, 13, 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, microsatellite instability was observed more frequently: ie, in six PA, five PHPT, and nine SHPT lesions. The profile of microsatellite instability depended on the type of proliferation: microsatellite instability (MI) seemed to cluster in the region of chromosome 11 in PA. Microsatellite instability on TP53 was observed in 3 of 6 PHPT lesions and in 2 of 47 SHPT lesions but in no PA lesions. Microsatellite instability on Mfd47 was observed in only some cases of SHPT. Although no significant correlation was identified among histologic features, clonality, and genetic abnormalities in cases of primary proliferation, genetic abnormalities 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 instability seems to be induced by different mechanisms in the three types of proliferation studied. In SHPT, the absence of fat tissues may indicate that the proliferation is accompanied by genetic changes.
Koshiishi
N
N
Department of Pathology, Jichi Medical School, Tochigi, Japan.
Chong
J M
JM
Fukasawa
T
T
Ikeno
R
R
Tanaka
A
A
Kanazawa
K
K
Ogura
M
M
Ebuchi
M
M
Takizawa
T
T
Funata
N
N
Fukayama
M
M
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000235:genetics; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D005260:Female; D016147:Genes, Tumor Suppressor; D006652:Histological Techniques; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D009857:Oncogenes; D010282:Parathyroid Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction