title: Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.
abstract: 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.
authors.affiliation: Department of Surgery, Walter Reed Army Medical Center, Washington, DC 20037,USA. ta.stojadinovic@verizon.net
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
authors.forename: Axel
authors.initials: A
authors.lastname: Hoos
authors.forename: Atilla
authors.initials: A
authors.lastname: Omeroglu
authors.forename: Denis H Y
authors.initials: DH
authors.lastname: Leung
authors.forename: Maria E
authors.initials: ME
authors.lastname: Dudas
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000473:pathology*; D018246:Adrenocortical Adenoma / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor