Adrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis

• Main Authors: Stojadinovic, A., Brennan, M. F., Hoos, A., Omeroglu, A., LEUNG, Denis H. Y., Dudas, M., Nissan, A., Cordon-Cardo, C., Ghossein, R.A.
• Format: text
• Language: English
• Published: Institutional Knowledge at Singapore Management University 2003
• Subjects: Econometrics; Medicine and Health Sciences
• Online Access: https://ink.library.smu.edu.sg/soe_research/384; https://ink.library.smu.edu.sg/context/soe_research/article/1383/viewcontent/3880834.pdf
• Institution: Singapore Management University

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P < .001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P < .001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P < .001) and was significantly associated with mitotic rate and unfavorable morphologic index (P < .001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation–associated proteins.