(P 331) MUSCULAR DEDIFFERENTIATION IN DEDIFFERENTIATED LIPOSARCOMA: INSIGHTS INTO INFLAMMATORY PROFILES USING THE NEUTROPHIL/LYMPHOCYTE RATIO AND PROGNOSTIC IMPLICATIONS

Objective: Soft tissue sarcomas comprise a diverse group of rare malignancies, with 15% originating in the retroperitoneum. These tumors often present at an advanced stage, leading to lower disease-free survival (DFS) and overall survival (OS), with recurrence rates approaching 50% in high-volume centers and OS reaching up to 60%. Dedifferentiated liposarcomas (ddLPS) are aggressive neoplasms, and the presence of dedifferentiated components is associated with increased distant recurrence and reduced OS. However, the impact of specific dedifferentiation subtypes and their association with systemic inflammatory profiles remains poorly understood.

Objective: To investigate the potential association between muscular dedifferentiation in ddLPS and systemic inflammatory profiles using the neutrophil-lymphocyte ratio (NLR) as a surrogate marker for inflammation and as an adverse prognostic factor.

Methods: We conducted a retrospective cohort study utilizing electronic medical records of patients diagnosed with primary retroperitoneal ddLPS between January 2005 and December 2018 at our institution. An immunohistochemical panel consisting of smooth muscle actin, calponin, H-caldesmon, desmin, and myogenin (MyoD) was employed to assess muscular dedifferentiation. Two expert sarcoma pathologists analyzed the samples, determining the presence or absence of these markers. The association of these markers with outcome measures, including DFS and OS, was examined. Additionally, the NLR cut-off point was established using receiver operating characteristic (ROC) curves, and a Pearson correlation analysis was conducted to assess the relationship between myogenic immunohistochemical variables and NLR.

Results: A total of 176 cases were included in the analysis, with 95 being liposarcomas and 50 identified as ddLPS. Among the ddLPS cases, 28 (56%) were male, and the mean age was 54.30 (±13.34) years, with a mean tumor size of 29.28 cm (±11.64 cm). The majority of patients (92%) had locally advanced disease classified as stage IIIB. Muscular dedifferentiation was observed in 30% (n=15) of the ddLPS cases. Although no significant differences were found between muscular dedifferentiation, treatment, and recurrence, distinct patterns emerged in terms of resection status, complications, and reoperations, with higher rates observed in the dedifferentiation group. Furthermore, the group with myogenic dedifferentiation exhibited lower OS (HR 5.08, 95% CI 2.274-11.384, p=0.0001) and DFS (HR 3.79, 95% CI 1.698-8.484, p=0.001). A moderate positive correlation (Pearson correlation: 0.380, p=0.006) was detected between myogenic immunohistochemical variables and NLR, further highlighting the potential association between muscular dedifferentiation and systemic inflammation.

Conclusion: The presence of markers of muscular differentiation is associated with unfavorable prognostic factors, including lower overall survival (OS) and disease-free survival (DFS). Additionally, we found a moderate positive correlation between myogenic immunohistochemical markers and NLR. These findings suggest the potential involvement of a systemic and possibly local (microenvironmental) inflammatory profile in the genesis and progression of ddLPS. Further studies are needed to elucidate the underlying mechanisms of this association and validate these findings.