Aberrations of centrosomes in adrenocortical tumors.
The frequent and generalized chromosomal imbalances that are characteristic of adrenocortical carcinomas suggest that incomplete chromosome segregation often takes place in these tumors. As a step towards elucidating the mechanism behind the multiple numerical chromosomal aberrations, we have evaluated a series of 14 such tumors for centrosome abnormalities using immunohistochemical detection of the gamma-tubulin centrosome component. The proportion of cells with more than the expected number of 2 centrosomes was moderately increased in the 4 adenomas (1-7%), while a high increase was observed in the 10 carcinomas (1-19%), as compared to the normal reference tissues (0.3%) (p<0.001). Similarly, the centrosome amplification tended to be more pronounced in the carcinomas where the aberrant cells carried 3 or 4 positive signals in 9 of the 10 tumors, and 6 signals were recorded in one tumor, while in the adenomas more than 3 signals was only recorded in one of the 4 cases. The findings demonstrate that centrosome amplifications occur frequently in both adrenocortical adenomas and carcinomas, thus supporting its role in driving the tumor development as opposed to being a consequence of it. Furthermore, the more pronounced occurrence in the malignant form as well as in the larger tumors, offers one likely explanation for the increasing generalized aneuploidy observed during the tumor development, and points to new therapeutic strategies aimed at restoring normal centrosome function.
Roshani
Leyla
L
Department of Molecular Medicine, Karolinska Hospital, CMM L8:01, SE-171 76 Stockholm, Sweden.
Fujioka
Kaoru
K
Auer
Gert
G
Kjellman
Magnus
M
Lagercrantz
Svetlana
S
Larsson
Catharina
C
D000236:Adenoma / Q000235:genetics; D000306:Adrenal Cortex Neoplasms / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D018385:Centrosome / Q000737:chemistry*; D020090:Chromosome Segregation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D014404:Tubulin / Q000032:analysis*
D014404:Tubulin