title: c-kit expression in primary and metastatic merkel cell carcinoma.
abstract: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.
authors.affiliation: Department of Pathology, Rabin Medical Center, Beilinson and Golda Campuses, Petah Tiqva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. meoraf@clalit.org.il
authors.forename: Meora
authors.initials: M
authors.lastname: Feinmesser
authors.forename: Marisa
authors.initials: M
authors.lastname: Halpern
authors.forename: Ella
authors.initials: E
authors.lastname: Kaganovsky
authors.forename: Baruch
authors.initials: B
authors.lastname: Brenner
authors.forename: Eyal
authors.initials: E
authors.lastname: Fenig
authors.forename: Emmilia
authors.initials: E
authors.lastname: Hodak
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Sulkes
authors.forename: Elimelech
authors.initials: E
authors.lastname: Okon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit