| Research Abstract |
We investigated the flow cytometric DNA content and nuclear grade in 43 adenomas associated with primary aldosteronism and 24 adenomas with Cushing's syndrome. Adenomas with primary aldosteronism had a significantly wider 4C peak on flow cytometric histogram than normal adrenal glands or adenomas with Cushing's syndrome (p<0.0001, respectively). Flow cytometric analysis showed diploidy in 30, tetraploidy in 27 and aneuploidy in 8 of the 67 adenomas, and all 17 normal adrenal glands showed diploidy. A significant correlation was noted between DNA ploidy and clinical syndrome, i.e., a larger proportion of adenomas with primary aldosteronism showed a tetraploid DNA histogram compared with adenomas with Cushing's syndrome (p=0.0004). Adenomas with primary aldosteronism had a significantly higher nuclear grade (III and IV) than did tumors with Cushing's syndrome (p=0.038). A significant correlation was also observed between DNA ploidy and nuclear grade in 57 nonaneuploid tumors, with tetrap
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loid tumors often showing the highest nuclear grade (p=0.042). Our results showed that adrenal cortical adenomas associated with primary aldosteronism often revealed severe nuclear pleomorphism, indicating that nuclear pleomorphism might be due to a tetraploid stemline.
DNA ploidy by flow cytometry and interphase fluorescence in situ hybridization (FISH) analysis of chromosome 3, 7, 8, 11, 12, and 17 were performed on 12 adrenal cortical adenomas (5 with Cushing's syndrome and 7 with primary aldosteronism). DNA ploidy analysis revealed 8 diploid and 4 tetraploid tumors, and DNA aneuploidy was not found in this study. Tetraploidy was found only in adenomas with primary aldosteronism, On the other hand, FISH analysis revealed some discrepancies between the chromosomal aberrations and DNA ploidy. Adenomas with primary aldosteronism showed tetrasomy in two or more chromosomes analyzed, irrespective of heir DNA ploidy. Adenomas with Gushing' s syndrome had fewer chromosomal abnormalities compared with tumors with primary aldosteronism. However, three of five AGAs with Cushing's syndrome had trisomy of chromosome 8, and in addition, adenomas with primary aldosteronism frequently showed trisomy of the same chromosome. These findings suggest that adenomas with primary aldosteronism may often have an aberrant (tetrasomic) stemline, and that trisomy of chromosome 8 may play an important role in the development of adrenal cortical adenoma. Less
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