The prognostic value of tumor microenvironment in endometrioid type endometrial cancer: Effect of CD44 on oncologic outcome

Objectives: The study aimed to evaluate the expression of CD44, CD47, interleukin-1 (IL-1), and tumor necrosis factor alpha (TNF-α) in immunohistochemically stained (IHS) samples from endometrioid endometrial cancer (EEC) and to examine their correlation with clinicopathologic parameters.

Methods: IHS was used to assess CD44, CD47, IL-1, and TNF-α expression in 53 EEC samples. Immunostaining was scored as negative (-), slightly positive (+), moderately positive (++), or strongly/diffuse positive (+++). The prognostic value of these markers was analyzed in relation to clinicopathologic features, including survival.

Results: In endometrial cancer tissues, positivity rates were CD44 (81%), CD47 (81%), TNF-α (40.5%), and IL-1 (42.9%). Strong and diffuse CD44 staining was associated with improved survival and linked to endocervical invasion and stage. Patients with slightly positive CD47 had significantly higher rates of pelvic and para-aortic lymph node metastases. Strong TNF-α staining correlated with grade 3 EEC, while slightly positive IL-1 staining was associated with increased endocervical invasion. No significant correlation was found between CD47, IL-1, and TNF-α expression and survival.

Conclusion: CD44 and CD47 were positive in most EEC specimens. CD44 expression was the only marker significantly correlated with overall survival and recurrence. TNF-α showed a positive correlation with high-grade tumors, and IL-1 staining was inversely associated with endocervical invasion. These findings suggest that CD44 is a prognostic marker for survival, while TNF-α and IL-1 may have indirect prognostic roles in EEC.