Histopathological and Clinical Perspectives on Prognostic Markers in Endometrial Cancer

The microcystic, elongated, and fragmented (MELF) invasion pattern, tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) may have prognostic value in endometrial carcinoma; however, their relationships are not fully defined. This retrospective study included 216 endometrioid endometrial carcinomas. MELF pattern, TB (BD1-3), and TIL levels were evaluated on hematoxylin-eosin sections. Clinicopathologic variables and immunohistochemical markers (HER2, p53, mismatch repair proteins) were analyzed statistically, including survival analysis.MELF pattern of invasion (present in 32.4%) was significantly associated with larger tumor size, low-to-intermediate grade, deep myometrial invasion, lymphovascular invasion (LVI), and nodal metastasis; on multivariate analysis, it remained independently associated with LVI (odds ratio=38.15) and nodal metastasis (odds ratio=12.82). TB was significantly associated with high-grade, deep invasion, cervical involvement, advanced FIGO stage, and mortality after Bonferroni correction; associations with tumor size, LVI, and nodal metastasis were significant only at the conventional threshold and considered trends. TB did not retain independent prognostic significance in the Cox regression model. TIL showed no significant association with any parameter, survival, or the other 2 patterns. MELF pattern of invasion is a clinically important marker independently associated with LVI and nodal metastasis. Notably, MELF was more common in low-to-intermediate grade tumors, suggesting that it may identify aggressive invasive behavior in tumors otherwise considered lower risk by grade alone. TB reflects aggressive tumor behavior without independent survival significance. TIL had limited prognostic value by routine assessment. Combined evaluation of MELF and TB may improve risk stratification in endometrioid endometrial carcinoma, particularly where molecular profiling is unavailable.