title: Association of immunohistochemical markers with premalignancy in Gonadal Dysgenesis.
abstract: BACKGROUND
  Gonadal dysgenesis (GD) is associated with increased risk of gonadal malignancy. Determining a patient's risk and appropriate timing of gonadectomy is challenging, but immunohistochemical markers (IHM) may help establish the diagnosis of malignant germ cell tumors (GCT). Our objective was to identify the prevalence of specific IHM expression in patients with GD and determine if the patterns of expression can help identify malignancy versus pre-malignancy state. We evaluated the published literature using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system to provide recommendations on the predictive role of IHM in the detection of germ cell malignancy.
  
  
  METHODS
  The data for this retrospective study included karyotype, gonadal location, external masculinization score, age at time of gonadectomy or biopsy, microscopic description and diagnosis of gonadal tissue, and immunohistochemical staining, including octamer binding transcription factor (OCT) 3/4, placental-like alkaline phosphatase (PLAP), β-catenin, alpha-fetoprotein (AFP), and stem cell factor receptor CD117 (c-KIT). Patients with complete or partial GD who had undergone gonadectomy or gonadal tissue biopsy were included.
  
  
  RESULTS
  The study included 26 patients with GD, 3 of whom had evidence of GCT (11.5 %, gonadoblastoma, dysgerminoma): 2 had Swyer syndrome, 1 had 46,XY partial GD. One patient with XY partial GD had gonadoblastoma-like tissue. All 4 patients (15 %) had strong expressions of 4 tumor markers (OCT 3/4, PLAP, β-catenin, CD117), as did 5 other patients (19 %, ages 2-14 months) without GCT: 4 had XY GD, 1 had 46,XX GD. β-catenin was expressed in 96 % of patients in a cytoplasmic pattern, CD117 in 78 %, OCT 3/4 in 55 %, PLAP in 37 %, and AFP in 1 patient (4 %). Tumor marker expression was not specific for ruling out malignancy in patients <1 year.
  
  
  CONCLUSIONS
  In patients older than 1 year, expression of all three markers (OCT 3/4, PLAP, CD117) may be instrumental in the decision-making process for gonadectomy, even in the absence of overt germ cell malignancy. Our literature review suggests that OCT 3/4 expression is most helpful in predicting risk of malignancy. Additional criteria are needed to stratify risk in patients younger than 1 year of age, as these markers are not reliable in that age group.
authors.affiliation: Division of Pediatric Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030 USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: McCann-Crosby
authors.affiliation: Division of Pediatric Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030 USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Gunn
authors.affiliation: Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030 USA.
authors.forename: E O'Brian
authors.initials: EO
authors.lastname: Smith
authors.affiliation: Division of Pediatric Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030 USA.
authors.forename: Lefkothea
authors.initials: L
authors.lastname: Karaviti
authors.affiliation: Department of Pathology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030 USA.
authors.forename: M John
authors.initials: MJ
authors.lastname: Hicks
keywords: Germ cell tumor; Gonadal dysgenesis; Gonadectomy; Immunohistochemical markers