The prognostic significance of cell adhesion molecules in endometrial carcinomas

Introduction and objective: Endometrial carcinoma is the most common gynecological cancer in postmenopausal women in developed countries. One of the major challenges encountered in the treatment of endometrial cancer is distinguishing patients who may benefit from adjuvant therapy from those who do not require additional treatment after surgery. According to current data, there is a discrepancy between risk groups determined by clinical-pathological criteria and recurrence rates observed in patients. Studies suggest that cell adhesion molecules such as L1 cell adhesion molecule (L1CAM; CD171) and beta-catenin may be potential biomarkers for predicting patient recurrence and prognosis. The aim of this study is to investigate the relationship between L1CAM and beta-catenin expression and clinical- pathological parameters, prognosis, recurrence, and survival in cases diagnosed with endometrioid endometrial carcinoma, the most common subtype of endometrial carcinoma. Materials and methods: In this study, a total of 141 cases who underwent staging surgery and were diagnosed with endometrioid endometrial carcinoma based on pathological examination at our hospital's Department of Pathology between January 2013 - December 2023. The most suitable slides in terms of tumor volume, fixation, and follow-up quality were selected. The histological diagnosis, histological grade, presence/depth of myometrial invasion, lymphovascular invasion, and presence of cervical stromal invasion were reevaluated for the cases. For immunohistochemical L1CAM expression, membrane staining of more than 10% in the tumor and nuclear staining for beta-catenin was considered positive. Data on age, disease stage, tumor grade, lymphovascular invasion, lymph node metastasis status, recurrence, overall survival, and disease-free survival were recorded for the cases. The relationship between L1CAM and beta-catenin expression and clinical-pathological parameters and their effect on survival were calculated using statistical analysis. Results: Of the 141 cases included in the study, 28 (19.9%) were L1CAM- positive and 20 (14.2%) were beta-catenin-positive. A statistically significant relationship was found between L1CAM expression and disease progression and recurrence. When analyzed using the Log Rank test, it was found that cases showing L1CAM expression had lower disease-free survival times. A statistically significant relationship was found between beta-catenin expression and young age and myometrial invasion of less than 50%. It was statistically significant that beta-catenin- positive cases were more common in the low-risk and less common in the low-to- intermediate-risk among risk groups classified according to tumor stages. Conclusions: L1CAM is a candidate for an important biomarker in predicting disease progression and recurrence. In our study, the higher incidence of recurrence and shorter disease-free survival in L1CAM-positive cases is promising for the more accurate identification of patients who will receive adjuvant therapy in the future and for patient management. Although beta-catenin as an adhesion molecule is seen in young, low-risk patients, its predictive value for recurrence, as mentioned in the literature, could not be confirmed in our study. This result suggests that the CTNNB1 mutation, which is responsible for the metastasis/recurrence pathogenesis, and its surrogate, immunohistochemical beta-catenin staining, may not overlap with sufficient sensitivity.