THE PREVALENCE AND PROGNOSTIC IMPACT OF L1 CAM, CDX2, P53 AND MICRO-SATELLITE INSTABILITY STATUS IN UTERINE CARCINOSARCOMA

Introduction: Uterine Carcinosarcomas (UCS) are a rare type of aggressive gynecological tumors composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS, such as sarcoma predominance, are well stablished, but studies that approach the impact of biomarkers in this unusual disease are scarce. The L1-cell adhesion molecule (L1CAM), highly expressed in ovarian and endometrial carcinomas, correlates with poorer prognosis, and the Caudal-related homeobox transcription factor 2 (CDX2) is associated with divergent prognostic impacts at extra-colorectal sites. These molecules pose examples of possible prognostic biomarkers underexplored in UCS. Mutated TP53 genes and Microsatellite Instability, both involved in carcinogenesis, also could be of great importance in establishing prognosis in UCS. In this manner, accessible biomarkers with clinical utility for the management of UCS still poses an unmet need. Objective: To evaluate the prevalence and prognostic impact of a panel of four prominent immunohistochemical biomarkers in UCS. Methods: The database of a single Brazilian institution was explored to select women diagnosed with UCS submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. Results: A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). Conclusion: The strong influence of CDX2 on prognosis suggests a more aggressive tumor subtype. The status of the other markers did not impact survival outcomes.