C-kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance

Janice V. Scobie, Geza Acs, Géza Ács, Christina A. Bandera, Stephanie V. Blank, James E. Wheeler, T Pasha, Teresa L. Pasha, Marilyn Salscheider, Paul J. Zhang
International Journal of Gynecological Pathology · 2003 · vol. 22(2) , pp. 149–155 · doi:10.1097/00004347-200304000-00006 · PMID:12649669 · W2065618440
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This study evaluated c-kit immunoreactivity in 72 endometrial adenocarcinomas, finding that its expression correlated with myometrial invasion depth and was associated with metastases and shorter disease-free survival.

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This study evaluated c-kit immunoreactivity in 72 endometrial adenocarcinomas to determine its clinicopathologic significance. Researchers found that cytoplasmic c-kit expression was present in 58% of tumors and correlated significantly with deeper myometrial invasion, metastases, and shorter disease-free survival. The authors suggest that c-kit positivity may serve as an adverse prognostic indicator and that patients with advanced c-kit-positive disease might benefit from tyrosine-kinase-inhibitor therapy. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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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.
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C-Kit Immunoreactivity in Endometrial Adenocarcinomas and Its Clinicopathologic Significance - Janice V. Scobie - Geza Acs - Christina A. Bandera - Stephanie V. Blank - James E. Wheeler - Teresa L. Pasha - Marilyn Salscheider - Paul J. Zhang Summary: 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.

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MeSH descriptors

Adenocarcinoma Endometrial Neoplasms Proto-Oncogene Proteins c-kit Adenocarcinoma Adenocarcinoma Adenocarcinoma Adult Aged Aged, 80 and over Endometrial Neoplasms Endometrial Neoplasms Endometrial Neoplasms Female Humans Immunohistochemistry Middle Aged Prognosis Proto-Oncogene Mas Proto-Oncogene Proteins c-kit

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