Introduction/Background Transforming growth factor-beta (TGF-β) has a crucial role in inducing endometrial cancer invasion and metastasis. Studies assaying this signalling pathway in endometrial cancers have been conflicting. Most of these have utilised cancer cell lines. Our research was to assess the TGF-β signalling pathway alterations in fresh tumour tissue specimens, including all subsets of endometrial cancers employing quantitative RNA assay techniques.

Methodology A prospective observational study was done on patients who underwent surgical staging for endometrial cancer from November 2020 to March 2021 at a tertiary cancer centre. Tumour samples from hysterectomy specimens were studied for mRNA levels of TGF-β1 ligand, TGF-β receptor1 & 2 (TGFβRI&II), Smad2 and Smad4 genes. mRNA expression was quantified by delta Ct (ΔCt) values obtained from quantitative PCR tests and fold change in expression by ΔΔCt values from ΔCt of reference endometrial sample. The association of these mRNA expressions with tumour-related characteristics and recurrences was assessed using non-parametric tests as Mann-Whitney U test & Kruskal Wallis test.

Results 49 patients were considered for analysis. Majority were of endometrioid histology, lower grade, and stage I. 84% of endometrial cancer samples demonstrated under-expression of Smad2. Loss of Smad2 was significantly associated with myo-invasive tumours and tumours >2 cm. Loss of TGFβRII expression was related to parametrial invasion and stage IV disease, while reduced TGFβRI expression to clear cell histology. During a median follow up of 15.4 months, there were three recurrences. Loss of TGFβRII expressions was significantly associated with recurrence. Mean ΔΔCt value of >1.950 for smad2 and TGFβRII expression was associated significantly with a reduced 1.5 year recurrence-free survival.

Conclusion TGFβ pathway components undergo changes in endometrial cancer. Impaired expression is observed at every level of signalling pathway, Loss of Smad mRNA expression and TGFβ receptor levels have certain associations with aggressive features and can predict recurrence risk.