Adrenocortical adenoma and carcinoma: Histopathological and molecular comparative analysis Journal Article
| Authors: | Stojadinovic, A.; Brennan, M. F.; Hoos, A.; Omeroglu, A.; Leung, D. H. Y.; Dudas, M. E.; Nissan, A.; Cordon-Cardo, C.; Ghossein, R. A. |
| Article 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 (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. |
| Keywords: | immunohistochemistry; adolescent; adult; child; controlled study; human tissue; protein expression; aged; aged, 80 and over; child, preschool; middle aged; major clinical study; clinical feature; histopathology; molecular genetics; follow up; methodology; ki 67 antigen; cell proliferation; mitosis; cell cycle; gene overexpression; protein bcl 2; metastasis; gene expression profiling; tumor markers, biological; protein; protein p53; tumor marker; adrenal cortex carcinoma; molecular marker; statistical analysis; adenoma; protein p27; tumor cell; carcinoma; outcomes research; mitosis rate; neoplasm invasiveness; dna microarray; tissue microarray; cyclin d1; protein p21; adrenocortical carcinoma; protein mdm2; adrenal cortex neoplasms; tumor necrosis; adrenal; ihc; adrenocortical adenoma; humans; prognosis; human; male; female; priority journal; article; adrenal cortex adenoma |
| Journal Title: | Modern Pathology |
| Volume: | 16 |
| Issue: | 8 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2003-08-01 |
| Start Page: | 742 |
| End Page: | 751 |
| Language: | English |
| DOI: | 10.1097/01.mp.0000081730.72305.81 |
| PUBMED: | 12920217 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work