Loss of SMARCB1 Expression Confers Poor Prognosis to Sinonasal Undifferentiated Carcinoma

Abstract

Background 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 SMARCB1 (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 SMARCB1 in SNUC and to analyze and compare the survival outcomes in SNUC patients with and without SMARCB1 expression. Methods 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 SMARCB1 status by immunohistochemistry (IHC). Clinical parameters were analyzed using Student's t -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). Results Fourteen cases of SNUC were identified. Approximately two-thirds (64%; n = 9) of patients were male and the majority (79%; n = 11) were between fifth to seventh decade. Skull base and orbital invasion were seen in 79% ( n = 11) and 93% ( n = 13) of cases, respectively. Fifty-seven percent of tumors ( n = 8) retained SMARCB1 expression by IHC (SR-SNUC), while the remaining 43% ( n = 6) showed loss of SMARCB1 expression and, thus, were considered as SMARCB1 -deficient (SD-SNUC). Although clinicopathological features and treatment modalities were similar, SD-SNUC showed poorer (OS: p = 0.07; disease free survival [DFS]: p = 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; p = 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). Conclusion SNUC represents a heterogeneous group of undifferentiated sinonasal malignancies. Based on the status of SMARCB1 expression, the two subgroups SD-SNUC and SR-SNUC appear to represent distinct clinical entities, with loss of SMARCB1 expression conferring an overall worse prognosis.

Keywords: INI-1; SMARCB1; cancer; sinonasal; survival; undifferentiated.

Fig. 1

Flowchart depicting selection of cases for the study.

Fig. 2

Histology of one SR-SNUC case and one SD-SNUC case. Hematoxylin and eosin (H&E) stained section of the SR-SNUC case demonstrates squamoid morphology characterized by tumor cells with abundant eosinophilic cytoplasm and distinct cell borders (A, ×20); IHC for SMARCB1 shows strong nuclear staining in the tumor cells (B, ×20). The SD-SNUC case shows basaloid morphology characterized by tumor cells with high nuclear to cytoplasmic ratio (C, H&E, ×20); SMARCB1 nuclear expression is lost in the tumor cells and retained in the background nonneoplastic inflammatory and stromal cells (D, ×20). SD-SNUC, SMARCB1 -deficient sinonasal undifferentiated carcinoma; SR-SNUC, SMARCB1 -retained SNUC.

Fig. 3

Comparison of Kaplan–Meier survival curves for overall survival between SR-SNUC and SD-SNUC. X axis denotes the duration of survival (in days) and Y axis denoted the cumulative survival. Vertical lines on each of the curves denote censored patients. SD-SNUC, SMARCB1 -deficient sinonasal undifferentiated carcinoma; SR-SNUC, SMARCB1 -retained SNUC.

Fig. 4

Comparison of Kaplan–Meier survival curves for disease free progression survival between SR-SNUC and SD-SNUC. X axis denotes the duration of survival (in days) and Y axis denoted the cumulative survival. Vertical lines on each of the curves denote censored patients. SD-SNUC, SMARCB1 -deficient sinonasal undifferentiated carcinoma; SR-SNUC, SMARCB1 -retained SNUC.

Fig. 5

Comparison of overall survival less than and more than 1 year between SR-SNUC and SD-SNUC. X axis denotes the duration of DFS and Y axis denoted the proportion of patients. Values inside each of these boxes represent respective proportion of patients. OS, overall survival; SD-SNUC, SMARCB1 -deficient sinonasal undifferentiated carcinoma; SR-SNUC, SMARCB1 -retained SNUC.

Fig. 6

Comparison of disease free survival less than and more than one year between SR-SNUC and SD-SNUC. X axis denotes the duration of DFS and Y axis denoted the proportion of patients. Values inside each of these boxes represent respective proportion of patients. DFS, disease free survival; SD-SNUC, SMARCB1 -deficient sinonasal undifferentiated carcinoma; SR-SNUC, SMARCB1 -retained SNUC.