Clonal and Kinetic Profiles Correlate with Vascular Patterns in Adrenal Cortical Lesions

Background: Monoclonal adrenal cortical lesions have been characterized by an inverse correlation between proliferation and apoptosis, while polyclonal lesions reveal a direct correlation. Their relationship with the vascular pattern remains unknown in nodular hyperplasias (ACNH), adenomas (ACA), and carcinomas (ACC) of the adrenal cortex.
Methods: We studied 20 ACNH, 25 ACA, and 10 ACC, classified according to WHO's criteria, from 55 females. Representative samples were histologically evaluated and microdissected to study clonality by X-chromosome inactivation. Proliferation (PR and apoptosis were evaluated in consecutive sections usin slide and flow cytometry, as well as in situ end labeling (ISEL). Endothelial cells were stained with CD31 and the blood vessel area and density quantified by image analysis in the same areas. Appropriate tissue controls were run in every case. Regression analyses between kinetic and vascular features were performed in both polyclonal and monoclonal lesions
Results: Polyclonal pattern was observed in 14/18 informative ACNH-22 informative .ACA, and monoclonal in 4/18 ACNH 19/22 ACA, and 9/9 ACC. A direct correlation between proliferatlon and apoptosis was observed in polyclonal lesions (PR= 29!.2 ISEL - 1.93), while that correlation was inverse for monoclonal lesions (PR = - 9.13 ISEL + 21.57). A pro ressive increase in blood vessel area was observed in the transition AC& - ACA - ACC, but statistically significant only between benign and malignant lesions (191:365168.32 vs. 958.07*1279.86 pm2, p<0.0001). In addition, case stratification by clonal pattern revealed significant differences between polyclonal and monoclonal benign lesions: 6% qolyclonal vs. 57% monoclonal lesions had blood vessel area > 186 pm P=0.0000008). Vessel area inversely correlated with both apoptosis and proliferation in polyclonal lesions and with apoptosis in,monoclonal lesions (Vessel Area = -5.50 ISEL +278.8&. Proliferation showed a direct correlation with blood vessel area in monoclonal lesions Vessel Area=5.05PR+168.13).
Conclusions: The kinetic advantage of monoclonal adrenal cortical lesions (proliferation, apoptosis) is maintained by an increased vascular area.