title: Classification of Indeterminate Melanocytic Lesions by MicroRNA Profiling.
abstract: OBJECTIVE
  Identification of indeterminate melanocytic skin lesions capable of neoplastic progression is suboptimal and may potentially result in unnecessary morbidity from surgery. MicroRNAs (miRs) may be useful in classifying indeterminate Spitz tumors as having high or low risk for malignant behavior.
  
  
  METHODS
  RNA was extracted from paraffin-embedded tissues of benign nevi, benign Spitz tumors, indeterminate Spitz tumors, and Spitzoid melanomas in adults (n = 62) and children (n = 28). The expression profile of 12 miRs in adults (6 miRs in children) was analyzed by real-time polymerase chain reaction.
  
  
  RESULTS
  Benign Spitz lesions were characterized by decreased expression of miR-125b and miR-211, and upregulation of miR-22, compared with benign nevi (p < 0.05). A comparison of Spitzoid melanomas to benign nevi revealed overexpression of miR-21, miR-150, and miR-155 in the malignant primaries (p < 0.05). In adults, Spitzoid melanomas exhibited upregulation of miR-21, miR-150, and miR-155 compared with indeterminate Spitz lesions. Indeterminate Spitz lesions with low-risk pathologic features had lower miR-21 and miR-155 expression compared with Spitzoid melanoma tumors in adults (p < 0.05), while pathologic high-risk indeterminate Spitz lesions had increased levels of miR-200c expression compared with low-risk indeterminate lesions (p < 0.05). Pediatric Spitzoid melanomas exhibited increased miR-21 expression compared with indeterminate Spitz lesions (p < 0.05). Moreover, miR-155 expression was increased in indeterminate lesions with mitotic counts >1 and depth of invasion >1 mm, suggesting miR-155 expression is associated with histological characteristics.
  
  
  CONCLUSIONS
  miR expression profiles can be measured in indeterminate Spitz tumors and correlate with markers of malignant potential.
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Latchana
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH, USA.
authors.forename: Sara E Martin
authors.initials: SE
authors.lastname: Del Campo
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH, USA.
authors.forename: Valerie P
authors.initials: VP
authors.lastname: Grignol
authors.affiliation: Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Clark
authors.affiliation: Department of Surgery, Upstate University Hospital, Syracuse, NY, USA.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Albert
authors.affiliation: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Aldrink
authors.affiliation: Department of Pathology, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Nicol
authors.affiliation: Department of Hematology/Oncology, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ranalli
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Peters
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gru
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Trihka
authors.affiliation: Institute of Informatics, Washington University, St. Louis, MO, USA.
authors.forename: Philip R O
authors.initials: PR
authors.lastname: Payne
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH, USA.
authors.forename: J Harrison
authors.initials: JH
authors.lastname: Howard
authors.affiliation: Department of Surgery, The Ohio State University, Columbus, OH, USA. William.Carson@osumc.edu.|Department of Molecular Virology, Immunology and Medical Genetics, The Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA. William.Carson@osumc.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D018332:Nevus, Epithelioid and Spindle Cell / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis; D012878:Skin Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs