SMARCB1 and RB1 Gene: Novel Mutations in Neuroendocrine Tumors of Sinonasal Cavity

Introduction: The loss of SMARCB1 expression has recently been reported in ~40% of sinonasal undifferentiated carcinoma (SNUC) and has been shown to portend a poor prognosis. Currently, few studies have been conducted on the frequency of its expression in neuroendocrine tumors (NET).

The loss of RB1 expression has been recently reported in ~50% of small cell lung cancers, which is an aggressive NET with a poor prognosis. However, there have been no studies conducted on the frequency of expression of RB1 in sinonasal NETs. This study is the first to investigate the status of both the SMARCB1 and RB1 expression in various sinonasal NETs and their clinical significance.

Methods: All patients with sinonasal NETs treated with curative intent from 2009 to 2020 at two tertiary care centers were included. Formalin-fixed paraffin-embedded archived samples were used to perform immunohistochemical analysis for SMARCB1 and RB1. Electronic records were used to collect pretreatment (age, gender, primary site, stage), treatment-related (type, approach, chemoradiotherapy), and outcome variables (disease-free survival [DFS] and overall survival [OS] duration).

Results: Fifty patients were analyzed. The various histopathological diagnoses included were poorly differentiated carcinoma (PDC, n = 21; 42%), sinonasal neuroendocrine carcinoma (SNEC, n = 14; 28%) and esthesioneuroblastoma (EB, n = 15, 30%).

Loss of SMARCB1 expression was observed in 14% of PDC (3/21) while, it was retained in all cases of SNEC and EB. Loss of expression of RB1 was observed in 25% (¼; *10 cases were not tested for RB1) of SNEC and 13% (2/15) of EB while, it was retained in all cases of PDC. None of the cases showed loss of expression of both markers.

SMARCB1-deficient (SD)-PDC had a significantly younger age at presentation than SMARCB1-retained (SR) PDC (42.63 vs. 60.67 years; p = 0.04). There was no significant difference in the survival outcomes: DFS (21.2 vs. 35.55 months; p = 0.61), OS (26.3 vs. 37.87 months; p = 0.68).

For EB, it was noted that age at diagnosis was significantly lower in RB-1 deficient (RD)-EB (38.3 vs. 63.96 months; p = 0.04) in comparison to RB-1 retained (RR)-EB. However, survival outcomes were statistically similar: DFS (RD versus RR: 110 vs. 55.47 months; p = 0.21), OS (110 vs. 78.18 months; p = 0.57).

For SNEC, both RD- and RR-SNEC had comparable DFS (RD versus RR: 6.26 versus 46.48; p = 0.33) and OS (6.26 months versus 48.85 months; p = 0.27). Additionally, age at diagnosis was also similar (RD versus RR: 60.8 versus 57.8 months; p = 0.76).

Conclusion: In contrast to SNUC, loss of SMARCB1 expression is noted to be extremely rare in NETs of the sinonasal cavity. If detected, it is more likely to be found in PDC. Similarly, loss of RB1 expression is rarely observed in NETs and if present is more likely to be found in SNEC. Additionally, none of the cases showed a loss of expression of both markers. The clinical effect of loss of gene expression likely depends on the histopathological subtype. Loss of expression in poorly differentiated carcinoma and esthesioneuroblastoma was noted to correlate with earlier age of presentation. Further studies need to be conducted to include a larger sample size to confirm these findings.

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Artikel online veröffentlicht:
15. Februar 2022