Analysis of IGF and IGFBP as prognostic serum biomarkers for adrenocortical carcinoma.
BACKGROUND
Adrenocortical carcinoma (ACC) lacks diagnostic and prognostic biomarkers to guide treatment. A consistently dysregulated pathway in ACC is the IGF signaling pathway, specifically overexpression of IGF2, IGF-I-receptor, and IGFBP2. The objective of this study was to perform a comprehensive analysis of serum IGF and IGFBP levels and to determine their utility as diagnostic and prognostic biomarkers in ACC.


METHODS
Preoperative serum samples from 53 patients who underwent surgery for adrenocortical adenomas, 3 patients who underwent initial surgery for ACC, 16 patients who underwent reoperative surgery for ACC, and 5 healthy volunteer controls were analyzed. The serum concentration of IGF1, IGF2, IGFBP1, IGFBP2, and IGFBP3 was determined by enzyme-linked immunosorbent assay.


RESULTS
No difference in the levels of IGF2 (p = .231) and IGFBP2 (p = .511) was observed between patients with ACC, benign adrenocortical tumors, and healthy volunteers. IGF1, IGFBP1, and IGFBP3 levels were not detected. High IGFBP2 levels were associated with better overall survival (OS) (p = .001) and showed a trend toward better abdominal progression-free (APFS) survival (p = .070) in patients with ACC. A subanalysis of patients undergoing reoperation for recurrent ACC showed better OS with high levels of IGFBP2 (p = .003) and a trend toward better APFS (p = .107). There was no significant difference in IGF2 and IGFBP2 levels by extent of disease.


CONCLUSIONS
IGF2 and IGFBP2 are not elevated in the serum of patients with ACC compared with patients with benign neoplasms and healthy volunteers. Elevated serum IGFBP2 is associated with better survival in patients with ACC and those undergoing reoperative surgery for recurrent ACC.
Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA, divot999@gmail.com.
Dhaval
D
Patel
Ryan
R
Ellis
Brandi
B
Howard
Myriem
M
Boufraqech
Sudheer Kumar
SK
Gara
Lisa
L
Zhang
Martha M
MM
Quezado
Naris
N
Nilubol
Electron
E
Kebebew
D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000175:diagnosis; D018268:Adrenocortical Carcinoma / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
D014408:Biomarkers, Tumor; C583557:IGF1 protein, human; C035170:IGF2 protein, human; C032231:IGFBP1 protein, human; C577903:IGFBP2 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II