title: C-kit expression of melanocytic neoplasm and association with clinicopathological parameters and anatomic locations in Chinese people.
abstract: Distinct genetic aberrations between melanomas in different anatomical locations have been confirmed in recent years. However, the associations between immunohistochemical expression, tumor sites, and clinical parameters are not clear. We examined the correlation of protein expression and gene mutation of c-kit with clinicopathological parameters and lesion locations in patients with malignant melanoma (MM). We collected 170 melanocytic lesions, including 106 cutaneous MM from acral melanoma (AM) and nonacral melanoma (NAM) sites, 24 dysplastic nevi, and 40 common melanocytic nevi. Tissue microarray was constructed, and immunohistochemical expression for c-kit was assessed with correlation with clinical parameters. Mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing was also analyzed. Immunostaining scores for c-kit were found to be statistically higher in Dysplastic Nevi than in common melanocytic nevi and MM. In addition, cytoplasmic c-kit staining was significantly correlated with poor survival in patients with AM but not in those with NAM. Twenty-nine cases of MM (including 9 NAM and 20 AM) are analyzed for mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing, and no genetic mutation is found. Our findings confirm that KIT mutations, in contrast to previous white cohorts, are not common in both AM and NAM of the Chinese and do not necessarily correlate with c-kit expression. The significantly different association between the expression of c-kit immunoreactivities and the mortality risks of melanomas on acral versus nonacral sites might change site-specific targeted therapeutic concepts in melanoma in the future.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lin
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chang
authors.forename: Jar-Yi
authors.initials: JY
authors.lastname: Ho
authors.forename: Hsin-Chung
authors.initials: HC
authors.lastname: Lin
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Tsai
authors.forename: Chien-Ping
authors.initials: CP
authors.lastname: Chiang
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Gao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D002648:Child; D004252:DNA Mutational Analysis; D004416:Dysplastic Nevus Syndrome / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009508:Nevus, Pigmented / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis* / Q000235:genetics; D012878:Skin Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013624:Taiwan / Q000453:epidemiology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit