Abstract
BackgroundEndometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC). Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes.MethodsTrop-2 protein expression was quantified using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens from 118 patients who underwent surgical staging from 2001–9 by laparotomy for EEC. Clinicopathologic characteristics including age, stage, grade, lymphovascular space invasion, and medical comorbidities were correlated with immunostaining score. Univariate and multivariate analyses were performed for overall survival, disease-free survival, and progression-free survival in relation to clinical parameters and Trop-2 protein expression.ResultsClinical outcome data were available for 103 patients. Strong Trop-2 immunostaining was significantly associated with higher tumor grade (p=0.02) and cervical involvement (p<0.01). Univariate analyses showed a significant association with reduced disease-free survival (DFS) (p=0.01), and a trend towards significance for overall and progression-free survival (p=0.06 and p=0.05, respectively). Multivariate analyses revealed Trop-2 overexpression and advanced FIGO stage to be independent prognostic factors for poor DFS (p=0.04 and p <0.001, respectively).ConclusionsTrop-2 protein overexpression is significantly associated with higher tumor grade and serves as an independent prognostic factor for DFS in endometrioid endometrial cancer.
Highlights
IntroductionTrop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC)
Endometrial cancer is the most common gynecologic malignancy in developed countries
We describe for the first time the clinicopathologic significance of Trop-2 overexpression in endometrial carcinomas (EEC) using a large number of specimens via tissue microarrays (TMAs)
Summary
Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC). Our group has demonstrated that Trop-2 expression is significantly higher in endometrioid endometrial carcinomas (EEC) compared to normal tissues representing both proliferative and secretory phase endometrium, and that strength of immunohistochemistry staining correlates with increasing grade. Compared to those that lack expression, EEC cell lines that overexpress Trop-2 are highly susceptible to antibody-dependent cellular cytotoxicity mediated by hRS7, a humanized monoclonal antibody against Trop-2 [24]
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