title: Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations.
abstract: Risk assessment for atypical Spitz tumors remains an enigma for physicians. Many prognosticators including sentinel lymph node biopsy fail to show the same prognostic significance in these tumors as seen in conventional melanoma. We conducted a case-controlled collaborative study involving multiple major melanoma treatment centers in the United States and Australia. Sixty-four atypical Spitz tumors with 5 years of uneventful follow-up and 11 atypical Spitz tumors resulting in advanced locoregional disease, distant metastasis, or death were evaluated by fluorescence in situ hybridization using 2 probe sets targeting 6 chromosomal loci. Predetermined criteria were utilized to detect the presence or absence of copy number aberrations for each locus. Logistic regression analysis, Fisher exact test, and multivariate analysis were performed to determine chromosomal copy number aberrations with statistically significant association with aggressive clinical behavior. Gains in 6p25 or 11q13 and homozygous deletions in 9p21 had statistically significant association with aggressive clinical behavior with P-values of 0.02, 0.02, and <0.0001, respectively. In multivariate analysis, homozygous 9p21 deletion was highly associated with clinically aggressive behavior (P<0.0001) and death due to disease (P=0.003). Fluorescence in situ hybridization detecting a limited number of chromosomal copy number aberrations can provide clinically useful and statistically significant risk assessment for atypical Spitz tumors. Cases with homozygous 9p21 deletions have the greatest risk. Cases with 6p25 or 11q13 gains also have higher risk for aggressive clinical behavior than FISH-negative atypical Spitz tumors or cases with 6q23 deletions.
authors: Department of Dermatology and Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Pedram
authors: P
authors: Gerami
authors: Richard A
authors: RA
authors: Scolyer
authors: Xiaowei
authors: X
authors: Xu
authors: David E
authors: DE
authors: Elder
authors: Ronnie M
authors: RM
authors: Abraham
authors: Douglas
authors: D
authors: Fullen
authors: Victor G
authors: VG
authors: Prieto
authors: Philip E
authors: PE
authors: Leboit
authors: Raymond L
authors: RL
authors: Barnhill
authors: Chelsea
authors: C
authors: Cooper
authors: Pedram
authors: P
authors: Yazdan
authors: Joan
authors: J
authors: Guitart
authors: Ping
authors: P
authors: Liu
authors: Ekaterina
authors: E
authors: Pestova
authors: Klaus
authors: K
authors: Busam
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002869:Chromosome Aberrations; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018332:Nevus, Epithelioid and Spindle Cell / Q000235:genetics* / Q000473:pathology*; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult