Abstract
BackgroundKnowledge on immunosuppressive factors in the pathogenesis of endometrial cancer is scarce. The aim of this study was to assess Glycodelin (Gd) and its immunosuppressive isoform Glycodelin A (GdA) in endometrial cancer tissue and to analyze its impact on clinical and pathological features and patient outcome.Methods292 patients diagnosed and treated for endometrial cancer were included. Patient characteristics, histology and follow-up data were available. Gd and GdA was determined by immunohistochemistry and in situ hybridization was performed for Gd mRNA.ResultsEndometrial cancer shows intermediate (52.2%) or high (20.6%) expression for Gd in 72.8%, and GdA in 71.6% (intermediate 62.6%, high 9.0%) of all cases. The glycosylation dependent staining of GdA is tumour specific and correlates with the peptide-specific Gd staining though neither of the two is associated with estrogen receptor, progesterone receptor or clinic-pathological features. Also Gd protein positively correlates with Gd mRNA as quantified by in situ hybridization. Gd positive cases have a favourable prognosis (p = 0.039), while GdA positive patients have a poor outcome (p = 0.003). Cox-regression analysis proofed GdA to be an independent prognostic marker for patient survival (p = 0.002), besides tumour stage, grade and the concomitant diagnosis of hypertension.ConclusionGd and GdA are commonly expressed in endometrial cancer tissue and seem to be of relevance in tumourigenesis. They differ not only in glycosylation but also in their biological activity, since only GdA holds prognostic significance for a poor overall survival in endometrial cancer patients. This finding might be explained by GdAs immunosuppressive capacity.
Highlights
Knowledge on immunosuppressive factors in the pathogenesis of endometrial cancer is scarce
Our former investigation showed that A87-B/D2 seems to be less restricted to Glycodelin A (GdA) carbohydrate structures than other monoclonal antibodies made in our laboratories, none of the three monoclonal antibodies recognize GdS or other pregnancy-related glycoproteins such as hCG or transferrin isolated from amniotic fluid [26]
Data of 291 cases analysed for Gd, 289 cases stained for GdA and 254 cases analysed for Gd mRNA were included in the statistical analysis
Summary
Knowledge on immunosuppressive factors in the pathogenesis of endometrial cancer is scarce. The aim of this study was to assess Glycodelin (Gd) and its immunosuppressive isoform Glycodelin A (GdA) in endometrial cancer tissue and to analyze its impact on clinical and pathological features and patient outcome. Some risk factors for the development of endometrial cancer have been described [3,4,5,6,7,8], though the exact. GdA holds several immunosuppressive abilities, which are best characterized in reproductive medicine [18]. These include the suppression of lymphocyte proliferation and inhibition of T- and B-cell activity [19,20,21]. The induction of apoptosis via GdA has been investigated [22]
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