Expression profiling of adrenocortical neoplasms suggests a molecular signature of malignancy.
BACKGROUND
Distinguishing between adrenocortical adenomas and carcinomas is often difficult. Our aim was to investigate the differences in transcriptional profiles between benign and malignant adrenocortical neoplasms using complementary DNA microarray techniques.


METHODS
We studied 7 patients with adrenocortical carcinomas and 13 with adenomas. Histopathology was reviewed in all patients; clinical follow-up was at least 1 year. Hybridizations were performed in duplicate against RNA reference. Expression levels were analyzed in the R environment for statistical computing with the use of aroma, limma, statistics, and class packages.


RESULTS
Transcriptional profiles were homogeneous among adenomas, while carcinomas were much more heterogeneous. Hierarchical clustering and self-organizing maps could separate clearly carcinomas from adenomas. Among genes that were most significantly upregulated in carcinomas were 2 ubiquitin-related genes (USP4 and UFD1L) and several insulinlike growth factor-related genes (IGF2, IGF2R, IGFBP3 and IGFBP6). Among genes that were most significantly downregulated in carcinomas were a cytokine gene (CXCL10), several genes related to cell metabolism (RARRES2, ALDH1A1, CYBRD1 and GSTA4), and the cadherin 2 gene (CDH2).


CONCLUSIONS
Through the use of cDNA arrays, adrenocortical adenomas and carcinomas appear to be clearly distinguishable on the basis of their specific molecular signature. The biologic importance of the up- and downregulated genes is yet to be determined.
Velázquez-Fernández
David
D
Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
Laurell
Cecilia
C
Geli
Janos
J
Höög
Anders
A
Odeberg
Jacob
J
Kjellman
Magnus
M
Lundeberg
Joakim
J
Hamberger
Bertil
B
Nilsson
Peter
P
Bäckdahl
Martin
M
D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation / Q000235:genetics