Immunosuppressive Glycodelin A is an independent marker for poor prognosis in endometrial cancer

Background: 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.
Methods: 292 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. Results: Endometrial 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.\%) 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. Conclusion: Gd 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.