title: Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal.
abstract: Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P=NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d.=5.6) versus 28% (s.d.=12.6, P<0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, P<0.01); nestin stained 83% (n=19/23 cases) versus 89% (16/18 cases, P=NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P=NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P=NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P=NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant.
authors.affiliation: Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Miller
authors.forename: Andrew
authors.initials: A
authors.lastname: Emley
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Richards
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: April
authors.initials: A
authors.lastname: Deng
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001900:Boston; D049109:Cell Proliferation; D051152:Clusterin / Q000032:analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008545:Melanoma / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D018193:Neoplasms, Complex and Mixed / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D010641:Phenotype; D011110:Polymorphism, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D055757:SOXE Transcription Factors / Q000032:analysis; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; C577484:NES protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D017475:Receptors, Nerve Growth Factor; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D019009:Proto-Oncogene Proteins c-kit; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf