KIT in Atypical Acral Nevi – An Immunohistochemical and Genetic Appraisal.
Elizabeth Park, Shi Yang, Andrew Emley, Kristen DeCarlo, Joanna Richards, Meera Mahalingam. Boston University School of Medicine, MA
Background: Mutations in KIT, present in up to 23% of acral melanomas, are clinically significant because of the availability of KIT-targeted therapies. A recent study indicates a correlation between KIT mutations and immunohistochemical expression of CKIT in acral melanoma. Given this, our aim was to confirm the utility of CKIT expression as a screening tool for KIT genotyping in atypical acral nevi – putative precursor lesions of melanoma. An additional aim was to ascertain the frequency of KIT mutations in atypical acral nevi.
Design: Immunohistochemical staining for CKIT was performed using a polyclonal rabbit anti-human C-KIT antibody. Staining criteria were the following: negative= staining in <10% of cells, 1= staining in 11-49% and 2= staining >50% of cells. Intensity was graded as follows: negative =0, weak staining = 1, moderate staining = 2 and strong staining = 3. Genomic amplification via PCR and direct sequencing were performed on KIT exons commonly mutated in acral melanomas such as 11, 13, and 17, from formalin-fixed paraffin-embedded tissue samples of atypical acral nevi (23) ranging in severity from mild (9), moderate (10), and severe (4). The control group included acral nevi without atypia (19) and acral melanoma (10). For purposes of statistical analyses: cases with 11% or more staining of cells were compared with negative cases and cases with a staining intensity of 1 or higher were compared with the negatives.
Results: Immunohistochemical analyses of acral nevi revealed the following: positive staining (11% or more) with an intensity 1 or more was noted in 18/22 (82%) of cases with atypia (5 with mild; 9 with moderate and 4 with severe atypia) and in 13/17 (76%) of cases without atypia. No statistically significant differences were noted between acral nevi with and without atypia in proportion and intensity of staining. Genomic analyses of exon regions revealed no abnormalities in “hotspots” frequently associated with point mutations in acral melanomas in acral nevi with and without atypia.
Conclusions: Our findings argue against the utility of immunohistochemical expression of CKIT as a method of prioritizing cases for KIT genotyping. Atypical acral nevi do not exhibit genetic alterations in “hotspots” frequently mutated in acral melanomas.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 122, Tuesday Morning