Can INI-1 (SMARCB1) Gene Determine the Survival Outcomes in Sinonasal Undifferentiated Carcinoma?

Introduction: The term “sinonasal undifferentiated carcinoma” (SNUC) refers to a large group of aggressive epithelial sinonasal malignancies without squamous or glandular features. Although, SNUC as a group demonstrates poor prognosis, it is not known if different subsets of SNUC exist that show different survival outcomes.

One of the recent genetic abnormalities reported in some undifferentiated sinonasal malignancies is loss of INI-1 (also known as SMARCB1) gene expression. On classifying SNUCs based on INI-1 staining, two different sub groups emerge—INI-1-deficient SNUC (ID-SNUC), which do not express INI-1 gene and INI-1 retained SNUC (IR-SNUC), which retain this gene expression.

To date, it is unknown whether these two subgroups behave differently. This study was conducted to compare the clinicopathological features and survival outcomes between the two.

Materials and Methods: Retrospective chart review of all SNUCs treated between 2006 and 2018 at a single tertiary care center was performed. Sixteen cases met the inclusion criteria out of which tissue samples were available for 15. Immunostaining for INI-1 was performed on tissue samples. Clinicopathological features and survival outcomes between IR-SNUC and ID-SNUC were compared.

Results: Of all the cases of SNUC, 47% were found to be ID-SNUC. 63% of the IR-SNUC and 86% of ID-SNUC had skull base involvement. Most cases (63% of IR-SNUC and 72% of ID-SNUC) were detected as multicompartmental masses rendering them to present at clinical stage IV based on TNM classification.

Demographics (age, gender, race, history of smoking, and alcohol intake), clinical features (ECOG functional status, Charlson’s comorbidity Index, primary tumor site, orbital, and skull base involvement) and pathological features (growth pattern, cytomorphology, necrosis, mitotic count, immunostaining with PanCK, p40, p63, p16, S100, synaptophysin, and chromogranin) were not significantly different between the two subgroups (p > 0.05).

Furthermore, pretreatment clinical features (duration from onset of symptoms to diagnosis, T-stage, N-stage, M-stage, overall AJCC stage) and treatment related variables (modality of treatment, surgical margin status, surgical approach, radiation technique, mean total radiation dose, days of interruptions during radiotherapy) were comparable (p > 0.05)

On analyzing the recurrence and survival outcomes, significant differences were observed between the two groups. Recurrence rate for IR-SNUC was 17% and for ID-SNUC was 60%. Overall survival time for the IR-SNUC (46.75 months) and ID-SNUC (11.75 months) trended toward statistical significance (p = 0.05). Disease-free survival time for IR-SNUC (31.75 months) and ID-SNUC (8.5 months) was significantly different between the two groups (p = 0.03). Overall 5-year survival probabilities were 1 (95% CI: 0.56–1) for IR-SNUC and 0 (95% CI: 0–0.43) for ID-SNUC.

Conclusion: Although both ID-SNUC and IR-SNUC have comparable clinicopathological and treatment related features, ID-SNUC demonstrates worse survival outcomes. Loss of INI-1 gene leads to dismal prognosis in a subset of SNUCs and therefore, it is encouraged to perform INI-1 staining in all cases of SNUC to stratify and prognosticate patients.

Suggestions: Further large-scale studies are necessary to determine if ID-SNUC represents a unique clinical entity and more importantly, whether it needs a distinct treatment algorithm.