Biological features of adrenal cortical neoplasms: flow cytometric, fluorescence in situ hybridization and immunohistochemical studies

K Takehara, MD, H Sakai, MD, T Shono, MD, H Kanetake, MD

Department of Urology, Nagasaki University School of Medcine, Nagasaki, Nagasaki Japan

AIM: We investigated the association between DNA ploidy, numerical chromosomal aberrations and proliferative activity in adrenal cortical neoplasms. METHODS: Our study included 12 adrenal cortical adenomas with hyperaldosteronism, 6 adenomas with Cushing syndrome, 3 non-functioning adenomas and 3 adrenal cortical cancers. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin-fixed paraffin-embedded tissues from the same materials were analyzed by flow cytometry for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki-67 and p53. For FISH analysis, we used centromere-specific probes for chromosomes 3, 7, 8, 11, 12 and 17. RESULTS: Of the 12 adenomas with hyperaldosteronism, 10 had a tetraploid DNA histogram, and 8, 9, 11, 6, 9 and 0 tumors had a tetrasomy of chromosomes 3, 7, 8, 11, 12 and 17 respectively. Few abnormal findings on DNA histogram and few numerical chromosomal aberrations were detected in adenomas other than adenomas with hyperaldosteronism. DNA aneuploidy and numerical aberrations of chromosome 17 were observed in 2 of 3 malignant tumors, and 2 had a strong p53 expression. The mean Ki-67 labeling index (LI) of adenomas and malignant tumors were 8.7 and 209.4, respectively. The Ki-67 LI and tumor size were significantly lower in adenomas with hyperaldosteronism than in adenomas with Cushing syndrome (p=0.004, respectively). CONCLUSIONS: Our study characterized the biological features of adrenal cortical tumors. Our results suggested that alterations of chromosome 17 might be an important event in the development of adrenal cortical malignant tumors.

KEY WORDS: adrenal cortex neoplasms, DNA ploidy, Ki-67 antigen, chromosome 17, p53 protein.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromosomal Aberrations.