title: C-kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance.
abstract: The proto-oncogene c-kit is a transmembrane-tyrosine-kinase receptor that is structurally related to the platelet-derived growth-factor receptor (PDGFR) and is involved in cell differentiation. C-kit has been found to be expressed in certain solid tumors and may play a role in their tumorigenesis. Recently, a tyrosine-kinase inhibitor specific for the PDGFR family, bcr-abl, and c-kit (STI571) has been reported to have therapeutic effects in tumors expressing the aberrant forms or high quantities of target proteins. Expression of c-kit has not been well evaluated in endometrial adenocarcinomas. In this study, c-kit immunoreactivity was evaluated on paraffin sections of 72 endometrial adenocarcinomas (57 endometrioid, 10 serous, and 5 clear cell) with a polyclonal antibody. Immunoreactivity of c-kit was analyzed semiquantitatively and correlated with various clinicopathologic factors. Cytoplasmic c-kit immunoreactivity was detected in 42 (58%) tumors. Thirty-four (60%) endometrioid, 8 (80%) serous, and 0 of the 5 clear-cell adenocarcinomas were c-kit positive. There was a significant correlation between c-kit positivity and the depth of myometrial invasion. Patients with c-kit-positive endometrial adenocarcinomas more frequently had metastases and shorter disease-free survival. Expression of c-kit may be a potentially adverse prognostic feature in endometrial adenocarcinoma. Patients with c-kit-positive advanced endometrial adenocarcinoma might benefit from tyrosine-kinase-inhibitor therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Janice V
authors.initials: JV
authors.lastname: Scobie
authors.forename: Geza
authors.initials: G
authors.lastname: Acs
authors.forename: Christina A
authors.initials: CA
authors.lastname: Bandera
authors.forename: Stephanie V
authors.initials: SV
authors.lastname: Blank
authors.forename: James E
authors.initials: JE
authors.lastname: Wheeler
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Pasha
authors.forename: Marilyn
authors.initials: M
authors.lastname: Salscheider
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit