title: High diagnostic and prognostic value of steroidogenic factor-1 expression in adrenal tumors.
abstract: 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.
authors.affiliation: Department of Internal Medicine I, University Hospital of Wuerzburg, Würzburg, Germany.
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmull
authors.forename: Guillaume
authors.initials: G
authors.lastname: Assie
authors.forename: Hans-Ullrich
authors.initials: HU
authors.lastname: Voelker
authors.forename: Luitgard
authors.initials: L
authors.lastname: Kraus
authors.forename: Melanie
authors.initials: M
authors.lastname: Beyer
authors.forename: Bruno
authors.initials: B
authors.lastname: Ragazzon
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Saeger
authors.forename: Jerome
authors.initials: J
authors.lastname: Bertherat
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1