SWI/SNF Complex-deficient Undifferentiated Carcinoma of the Gastrointestinal Tract

Abstract

Undifferentiated carcinoma of the gastrointestinal tract has variable rhabdoid features. Expression of switch/sucrose nonfermenting (SWI/SNF) complex subunits is reportedly lost in a portion of cases; however, the prognostic significance of this loss remains unknown. Herein, 30 undifferentiated carcinoma cases were assessed for the expression of 4 SWI/SNF complex subunits (SMARCB1, SMARCA2, SMARCA4, and ARID1A). Tumor origin sites comprised stomach (40.0%), large intestine (20.0%), small intestine (16.7%), lower esophagus and stomach fundus (13.3%), ileocecal junction (3.3%), rectum (3.3%), and pancreas (3.3%). The tumors were composed of epithelioid neoplastic cells arranged in diffuse solid or discohesive sheets, nests, cords, poor cohesive pseudoglandular, and trabecular patterns. Rhabdoid tumor cells were identified in 66.7% (20/30) of cases. In total, 29/30 (96.7%) showed complete loss of at least 1 SWI/SNF subunit: SMARCA4 − /SMARCA2 − (11), isolated SMARCA4 − (2), SMARCA4 − /SMARCA2 unknown (6), isolated SMARCA2 − (7), SMARCA2 − /ARID1A − (1), and isolated ARID1A − (2). Negative or decreased expression (≤10% positive) of pan-cytokeratin was observed in 58.6% (17/29) of cases. In addition, 66.7% (20/30) of patients were late-stage (III or IV), and 65.2% (15/23) of stage IIB to IV patients succumbed to the disease at a mean clinical follow-up of 12.7 months. Specifically, patients with loss of SMARCA4 expression had the worst overall survival ( P =0.028) and disease-free survival ( P =0.006) rates, compared with those with SMARCA4 expression. The loss or decreased expression of epithelial markers is thus common in SWI/SNF complex-deficient undifferentiated carcinoma of the gastrointestinal tract, and loss of SMARCA4 correlates with poor prognosis.