Improvement of histopathological classification of adrenal gland tumors by genetic differentiation

Abstract

Purpose: There are often problems in differentiating between benign and malignant adrenal gland tumors by imaging and histopathology. Fine-needle biopsy is possible but not used owing to problems in histopathological differentiation. On account of considerable differences in the therapy and aftercare of benign and malignant adrenal tumors, correct classification of tumor type is of greatest importance. The purpose of this study was to define specific genetic alterations differentiating between adenomas and carcinomas.

Methods: DNA was isolated from tumor areas in paraffin sections and amplified by a modified protocol for DOP-PCR. After labeling of tumor-DNA and normal DNA with biotin-dUTP and digoxigenin-dUTP, respectively, comparative genomic hybridization (CGH) was carried out according to standard protocols. Retrospectively, 26 (16 adenomas and 10 carcinomas) tumors of the adrenal cortex were analyzed.

Results: Genetic alterations were found in 5/16 adenomas (31.25%) and in all adrenocortical carcinomas. The mean number of genetic changes per tumor was 8.7 (range 6-12) in carcinomas. The benign cortical tumors present 1.6 changes (range 0-3) per tumor. Only a moderate correlation between number of alterations and size of tumor was seen. Furthermore, specific chromosomal alterations of carcinomas were identified.

Conclusions: Genetic evaluation facilitates differentiation between adrenal gland tumors. Genetic tests should be used in routine diagnostics of adrenal specimens. Potentially, fine-needle biopsy can be established as standard diagnostics of adrenal tumors with unknown genesis.