title: Impact of a second opinion using expression and molecular analysis of FOXL2 for sex cord-stromal tumors. A study of the GINECO group & the TMRO network.
abstract: OBJECTIVE
  Ovarian sex cord-stromal tumors (SCSTs) are rare and their diagnosis is often difficult to establish. Recently, immunostaining and molecular analysis for Forkhead box L2 (FOXL2) have been developed in this pathology. This study aims to assess the benefit of an algorithm incorporating these new tools for a better diagnosis and classification of SCSTs
  
  
  METHODS
  Seventy-two tumors with a potential diagnosis of SCSTs were addressed by 37 different pathologists to one French rare ovarian tumor expert center, member of the Rare Malignant Ovarian Tumor network (TMRO). Then a "second opinion" (SO) through an algorithm incorporating immunostaining (IHC) and molecular analysis of FOXL2 was performed for all these cases. This algorithm was then validated by all pathologists of the TMRO network.
  
  
  RESULTS
  After a second opinion including molecular analysis and immunostaining for FOXL2 the initial diagnosis was changed in 15 of 72 samples (21%). FOXL2 mutation was present in 44 out of 47 adult granulosa cell tumors (94%), in 3 out of 8 Thecomas (37%), in 1 out of 10 Sertoli-Leydig cell tumors (SLSTs) (10%) and in 3 out of 5 undifferentiated-SCSTs (Und-SCSTs) (60%). Immunoexpression of FOXL2 was available in 45 cases of SCSTs: FOXL2 was expressed in 44 of them (98%).
  
  
  CONCLUSIONS
  A second opinion in an expert center for all cases of SCSTs is fundamental to get an optimal classification of these rare tumors. This second opinion could be performed with an algorithm which integrates FOXL2 mutation and expression status of FOXL2 in order to standardize the practice.
authors.affiliation: Centre Léon Bérard, Lyon, France; Université Claude Bernard Lyon1 - Université de Lyon, Lyon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Maillet
authors.affiliation: Institut Roche de Recherche et Médecine Translationnelle, 92650 Boulogne Billancourt, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Goulvent
authors.affiliation: Centre Léon Bérard, Lyon, France; Inserm U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Université Claude Bernard Lyon1 - Université de Lyon, Lyon, France.
authors.forename: Ruth
authors.initials: R
authors.lastname: Rimokh
authors.affiliation: Hôpital Cochin, Assistance publique Hôpitaux de Paris, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Marie-Cecile
authors.initials: MC
authors.lastname: Vacher-Lavenu
authors.affiliation: Institut Gustave-Roussy, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.affiliation: Hôpital Cochin, Assistance publique Hôpitaux de Paris, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: Hôtel-Dieu - Assistance Publique Hôpitaux de Paris, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Laurraine
authors.affiliation: Inserm U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Hôpital de la Croix-Rousse - Hospices Civils de Lyon, Lyon, France.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.affiliation: Centre Léon Bérard, Lyon, France; Inserm U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. Electronic address: isabelle.treilleux@lyon.unicancer.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.affiliation: Centre Léon Bérard, Lyon, France; Université Claude Bernard Lyon1 - Université de Lyon, Lyon, France. Electronic address: isabelle.ray-coquard@lyon.unicancer.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Roche SAS Scientific Partnerships, 92650 Boulogne Billancourt, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
mesh_terms: D000465:Algorithms; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012017:Referral and Consultation; D018312:Sex Cord-Gonadal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors
keywords: Diagnostic; FOXL2 mutation; Granulosa cell tumors; Rare cancer; Second opinion; Sex cord-stromal tumors