High diagnostic and prognostic value of steroidogenic factor-1 expression in adrenal tumors.
BACKGROUND
No immunohistochemical marker has been established to reliably differentiate adrenocortical tumors from other adrenal masses. A panel of markers like melan-A and inhibin-α is currently used for this purpose but suffers from limited diagnostic accuracy. We hypothesized that expression of steroidogenic factor-1 (SF-1), a transcription factor involved in adrenal development, is of value for the differential diagnosis of adrenal masses and predicts prognosis in adrenocortical carcinoma (ACC).


METHODS
SF-1 protein expression was assessed by immunohistochemistry on tissue samples from 167 ACC, 52 adrenocortical adenomas (ACA), six normal adrenal glands, six normal ovaries and 73 neoplastic nonsteroidogenic tissues. In an independent cohort of 33 ACC and 58 ACA, SF-1 mRNA expression was analyzed. SF-1 expression was correlated with clinical outcome in patients with ACC.


RESULTS
SF-1 protein staining was detectable in 158 of 161 (98%) evaluable ACC samples including 49 (30%) with strong SF-1 staining and in all normal and benign steroidogenic tissues. In addition, SF-1 mRNA expression was present in all 91 analyzed adrenocortical tumors. In contrast, SF-1 expression was absent in all nonsteroidogenic tumors. Strong SF-1 protein expression significantly correlated with poor clinical outcome: tumor stage-adjusted hazard ratio for death 2.46 [95% confidence interval (CI) = 1.30-4.64] and for recurrence 3.91 (95% CI = 1.71-8.94). Similar results were obtained in the independent cohort using RNA analysis [tumor stage-adjusted hazard ratio for death 4.69 (95% CI = 1.44-15.30)].


CONCLUSIONS
SF-1 is a highly valuable immunohistochemical marker to determine the adrenocortical origin of an adrenal mass with high sensitivity and specificity. In addition, SF-1 expression is of stage-independent prognostic value in patients with ACC.
Sbiera
Silviu
S
Department of Internal Medicine I, University Hospital of Wuerzburg, Würzburg, Germany.
Schmull
Sebastian
S
Assie
Guillaume
G
Voelker
Hans-Ullrich
HU
Kraus
Luitgard
L
Beyer
Melanie
M
Ragazzon
Bruno
B
Beuschlein
Felix
F
Willenberg
Holger S
HS
Hahner
Stefanie
S
Saeger
Wolfgang
W
Bertherat
Jerome
J
Allolio
Bruno
B
Fassnacht
Martin
M
D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D054339:Steroidogenic Factor 1 / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1