Adrenocortical adenoma and carcinoma: Histopathological and molecular comparative analysis

Alexander Stojadinovic*, Murray F. Brennan, Axel Hoos, Atilla Omeroglu, Denis H.Y. Leung, Maria E. Dudas, Aviram Nissan, Carlos Cordon-Cardo, Ronald A. Ghossein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 (Le., 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.

Original languageEnglish
Pages (from-to)742-751
Number of pages10
JournalModern Pathology
Issue number8
StatePublished - 1 Aug 2003
Externally publishedYes


  • Adenoma
  • Adrenal
  • Carcinoma
  • IHC
  • Tissue microarray


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