Prognostic Role of Transforming Growth Factor-β Signaling Pathway Alterations in Endometrial Cancers: A Prospective Cohort Study

Molecular classification of endometrial cancer (EC) has opened avenues for the development of more prognostic biomarkers. Transforming growth factor-beta (TGF-β) may play a key role in the genesis of endometrial cancer.

This study aimed to assess the expression of components of the TGF-β signaling pathway in EC tumor specimens and to assess the association of their expression with histopathologic characteristics, recurrence risk, and progression-free survival (PFS).

A prospective observational study was conducted on patients who underwent surgical staging for EC. Tumor samples from hysterectomy specimens were studied for levels of mRNA of TGF-β1 ligand, TGF-β receptor1, receptor 2, SMAD2, and SMAD4 genes, using quantitative polymerase chain reaction tests and associations assessed.

Fifty patients were included in this analysis. Statistically significant under-expression of Smad2 was observed in EC samples. Smad under expression, evident in the early stages, seems to be lost in the presence of more aggressive features. There were 5 recurrences over a median follow-up period of 28 months. Recurrence and PFS were significantly associated with increased TGF-βRII values.

TGFβ pathway components undergo alterations in endometrial cancer. Recurrence and progression-free survival were significantly associated with TGFβRII under expression. Changes in TGF-β signaling may be a prognostic biomarker for endometrial cancer.