Loss of SMARCB1 Expression Confers Poor Prognosis to Sinonasal Undifferentiated Carcinoma

Abstract

<b>Background</b> Due to the diverse histopathologic features and variable survival rates seen in sinonasal undifferentiated carcinoma (SNUC), it is likely that this diagnostic entity is comprised of a heterogonous group of morphologically undifferentiated tumors. As advancements in molecular testing have led to a better understanding of tumor biology, it has become increasingly evident that SNUC may actually encompass several tumor subtypes with different clinical behavior. As a result, it is also likely that all SNUC patients cannot be treated in the same fashion. Recent investigations have identified loss of the tumor suppressor <i>SMARCB1</i> (INI1) expression in a subset of undifferentiated sinonasal tumors and extrasinonasal tumors and, studies have suggested that this genetic aberration may be a poor prognostic marker. The objective of this study was to identify differential expression of <i>SMARCB1</i> in SNUC and to analyze and compare the survival outcomes in SNUC patients with and without <i>SMARCB1</i> expression. <b>Methods</b> All cases of undifferentiated or poorly differentiated neoplasms of the sinonasal tract treated between 2007 and 2018 at a single tertiary care institution were selected. All cases of SNUC were tested for <i>SMARCB1</i> status by immunohistochemistry (IHC). Clinical parameters were analyzed using Student's <i>t</i> -test and Fischer's test. Kaplan-Meier methods were used to estimate survival durations, while comparison between both the subgroups was done using the log-rank test. Statistical analysis was performed with the use of SPSS software, Version 25 (IBM, New York, NY, United States). <b>Results</b> Fourteen cases of SNUC were identified. Approximately two-thirds (64%; <i>n</i> = 9) of patients were male and the majority (79%; <i>n</i> = 11) were between fifth to seventh decade. Skull base and orbital invasion were seen in 79% ( <i>n</i> = 11) and 93% ( <i>n</i> = 13) of cases, respectively. Fifty-seven percent of tumors ( <i>n</i> = 8) retained <i>SMARCB1</i> expression by IHC (SR-SNUC), while the remaining 43% ( <i>n</i> = 6) showed loss of <i>SMARCB1</i> expression and, thus, were considered as <i>SMARCB1</i> -deficient (SD-SNUC). Although clinicopathological features and treatment modalities were similar, SD-SNUC showed poorer (OS: <i>p</i> = 0.07; disease free survival [DFS]: <i>p</i> = 0.02) overall survival (OS) and DFS on Kaplan-Meier curves. Additionally, SD-SNUC showed higher recurrence (75 vs. 17%) and mortality (67 vs. 14%) (hazard rate = 8.562; <i>p</i> = 0.05) rates. Both OS (28.82 ± 31.15 vs. 53.24 ± 37.50) and DFS durations (10.62 ± 10.26 vs. 43.79 ± 40.97) were consistently worse for SD-SNUC. Five-year survival probabilities were lower for SD-SNUC (0.33 vs. 0.85). <b>Conclusion</b> SNUC represents a heterogeneous group of undifferentiated sinonasal malignancies. Based on the status of <i>SMARCB1</i> expression, the two subgroups SD-SNUC and SR-SNUC appear to represent distinct clinical entities, with loss of <i>SMARCB1</i> expression conferring an overall worse prognosis.