title: Expression of anaplastic lymphoma kinase in Merkel cell carcinomas.
abstract: This study examines the presence of anaplastic lymphoma kinase protein and anaplastic lymphoma kinase gene rearrangements in Merkel cell carcinomas. A total of 32 cases of Merkel cell carcinomas and 12 cases of small cell lung carcinomas were analyzed. Immunohistochemistry was performed using 3 different anaplastic lymphoma kinase antibody clones (D5F3, 5A4, and anaplastic lymphoma kinase 1). Tumors were divided into high (intensity score 2-3+ in ≥25% of the tumor cells) and low expressors (all other positive expression patterns). Anaplastic lymphoma kinase reactivity in Merkel cell carcinoma was observed in 93.8% (30/32) with clone D5F3, 87.5% (28/32) with clone 5A4, and 12.5% (4/32) with clone anaplastic lymphoma kinase 1. One small cell lung carcinoma (1/12; 8.3%) showed anaplastic lymphoma kinase low expression with clone D5F3. Anaplastic lymphoma kinase high expression was observed in 81.3% (26/32) of the Merkel cell carcinomas with clone D5F3, 71.9% (23/32) with clone 5A4, and none with clone anaplastic lymphoma kinase 1. The specificity of anaplastic lymphoma kinase expression in Merkel cell carcinoma versus small cell lung carcinoma was 91.7% with clone D5F3 and 100% with the clones 5A4 and anaplastic lymphoma kinase 1. Interphase fluorescence in situ hybridization with the anaplastic lymphoma kinase dual-color, break-apart rearrangement probe was performed on 10 randomly selected Merkel cell carcinoma anaplastic lymphoma kinase high expressors. No rearrangement or other cytogenetic aberration of the anaplastic lymphoma kinase gene locus was identified. In conclusion, the anaplastic lymphoma kinase protein was detected with high frequency in Merkel cell carcinomas and was useful in distinguishing Merkel cell carcinoma from small cell lung carcinoma. No correlation with anaplastic lymphoma kinase rearrangement was found. Our findings could have important therapeutic consequences for patients, but the role of anaplastic lymphoma kinase in the pathogenesis of Merkel cell carcinoma needs to be further elucidated.
authors.affiliation: Department of Pathology, Naestved and Slagelse Hospital, Hospital South, Denmark. bfil@regionsjaelland.dk
authors.forename: Bettina Ekvall
authors.initials: BE
authors.lastname: Filtenborg-Barnkob
authors.forename: Michael
authors.initials: M
authors.lastname: Bzorek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics; D008297:Male; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000201:enzymology / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Anaplastic lymphoma kinase; Immunohistochemistry; Merkel cell carcinoma