title: Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type.
abstract: The role of immunohistochemistry in the assessment of KIT status in melanomas, especially acral lentiginous/mucosal, is not well established. Although the reported prevalence of KIT mutations in acral lentiginous/mucosal melanomas is relatively low, detection of mutations in KIT can have profound therapeutic implications. We evaluated the efficacy of immunohistochemistry to predict mutations in KIT. One hundred seventy-three tumors, comprising primary and metastatic melanomas (141 acral lentiginous/mucosal, 5 nodular, 4 lentigo maligna, 3 superficial spreading, 2 uveal, 1 melanoma of soft parts, 8 metastases from unclassified primaries, and 9 metastases from unknown primaries) were studied. Immunohistochemical expression of KIT using an anti-CD117 antibody and KIT mutational analysis by gene sequencing of exons 11, 13, and 17 were performed. Eighty-one percent of acral lentiginous/mucosal melanomas, primary and metastatic, showed KIT expression by at least 5% of the tumor cells. The overall frequency of activating KIT gene mutations in acral lentiginous/mucosal melanomas was 15% (14 out of 91 cases), being the L576P mutation in exon 11 the most frequently detected (4 of 14 cases). Cases showing less than 10% positive tumor cells were negative for KIT mutations. Eighty-two percent (12 of 14) of cases positive for KIT mutation showed KIT expression in more than 50% of the cells. An association between immunohistochemical expression of KIT and mutation status was found (P=0.007). Immunohistochemical expression of KIT in less than 10% of the cells of the invasive component of acral lentiginous/mucosal melanomas appears to be a strong negative predictor of KIT mutation and therefore can potentially be used to triage cases for additional KIT genotyping.
authors.affiliation: Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030-4009, USA. ctcabala@mdanderson.org
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Torres-Cabala
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Trent
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Galbincea
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.forename: Scott
authors.initials: S
authors.lastname: Woodman
authors.forename: Michael
authors.initials: M
authors.lastname: Davies
authors.forename: Jose A
authors.initials: JA
authors.lastname: Plaza
authors.forename: J W
authors.initials: JW
authors.lastname: Nash
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.forename: Doina
authors.initials: D
authors.lastname: Ivan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D019009:Proto-Oncogene Proteins c-kit