title: microRNA in situ hybridization for miR-211 detection as an ancillary test in melanoma diagnosis.
abstract: Some melanocytic tumors can be histologically ambiguous causing diagnostic difficulty, which could lead to overtreatment of benign lesions with an unwarranted psychological distress or undertreatment of malignant cancers. Previously, we demonstrated that significantly decreased miR-211 expression in melanomas compared with melanocytic nevi could accurately discriminate malignant from benign tumors. Herein we show microRNA in situ hybridization for fluorescent detection of miR-211, suitable for paraffin-embedded tissues in 109 primary melanocytic tumors. miR-211 expression was significantly lower in melanomas vs nevi (P<0.0001), and receiver operating characteristic curve (area under the curve=0.862) accurately discriminated melanomas from nevi with 90% sensitivity and 86.2% specificity. Qualitatively, all dysplastic nevi expressed miR-211 at high (86%) and low (14%) levels, independent of the degree of nuclear atypia. All 35 melanocytic tumors with Spitz morphology expressed miR-211 independent of morphological classification, where clinical follow-up of these patients showed no recurrence at the site or metastasis in mean and median of 3 (ranging 2-5) years. Moreover, a decision tree learning analysis selected age and miR-211 miRNA in situ hybridization as the predictive variables for benign or malignant outcome in 88 patients correctly classified 92% (81 out of 88) of cases as proven by receiver operating characteristic curve (area under the curve=0.9029). These results support miR-211 as a leading miRNA candidate for melanoma diagnosis and miRNA in situ hybridization as a uniquely uncomplicated ancillary test.
authors.affiliation: Department of Genetics and Genomic Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Sankhiros
authors.initials: S
authors.lastname: Babapoor
authors.affiliation: Department of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Horwich
authors.affiliation: Connecticut Institute for Clinical and Translational Science Biostatics Center, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Affymetrix, Santa Clara, CA, USA.
authors.forename: Shauna
authors.initials: S
authors.lastname: Levinson
authors.affiliation: Affymetrix, Santa Clara, CA, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Gandhi
authors.affiliation: Department of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Hanspaul
authors.initials: H
authors.lastname: Makkar
authors.affiliation: Department of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Arni
authors.initials: A
authors.lastname: Kristjansson
authors.affiliation: Department of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Genetics and Genomic Sciences, University of Connecticut Health Center, Farmington, CT, USA.|Department of Dermatology, University of Connecticut Health Center, Farmington, CT, USA.|Department of Anatomic Pathology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Soheil S
authors.initials: SS
authors.lastname: Dadras
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D004416:Dysplastic Nevus Syndrome / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics; D035683:MicroRNAs / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000175:diagnosis / Q000235:genetics; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C549405:MIRN211 microRNA, human; D035683:MicroRNAs