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Relationship between flow cytometric DNA ploidy and nuclear grade with endocrine dysfunction in adrenal cortical
1Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan.
Objectives:
To determine the relationship among the DNA ploidy, histopathologic features, and clinical syndrome in adrenal cortical adenomas, because the cells often show variability in nuclear size and configuration.
Methods:
Our study included 44 adenomas associated with primary aldosteronism and 23 adenomas associated with Cushing syndrome. Normal adrenal glands from patients with renal carcinoma served as the controls. Paraffin-embedded tissues were examined for DNA content by flow cytometry. The mean percentage of G(2)/M (4C%) of the control samples was 3.8%. Tetraploid was represented by a histogram with both a 4C peak greater than 9% (mean + 2.4 SD of control samples) and a small 8C peak.
Results:
Flow cytometric analysis revealed diploidy in 30, tetraploidy in 27, and aneuploidy in 8 of the 67 adenomas; 2 adenomas could not be classified. All 17 normal adrenal glands showed diploidy. A significant relationship was noted between DNA ploidy and the clinical syndrome (ie, a larger proportion of adenomas with primary aldosteronism had a tetraploid DNA histogram compared with adenomas with Cushing syndrome, P <0. 0001). Adenomas with primary aldosteronism had a significantly higher nuclear grade (III or IV) than did tumors with Cushing syndrome (P = 0.033). A significant relationship was also observed between DNA ploidy and nuclear grade in 57 euploid tumors, with tetraploid tumors often showing the highest nuclear grade (P = 0. 037).
Conclusions:
Our results have demonstrated that adrenal cortical adenomas associated with primary aldosteronism often reveal severe nuclear pleomorphism, indicating that nuclear pleomorphism might be due to a tetraploid stemline.