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.

Switch/Sucrose Non-Fermentable Complex-Deficient Rhabdoid Carcinoma of Stomach: A Rare Case Report and Literature Review

“…Deletion of SWI/ SNF subunits usually leads to poor prognosis. 16,17,33 The mechanism by which deficiency of the SWI/SNF complex promotes oncogenesis remains ambiguous. But the loss of SWI/SNF leading to incomplete differentiation of tumor cells is certain.…”

“…Some patients achieved complete remission after chemotherapy with the xelox regimen. 17 One study referring to SWI/SNF-altered NSCLC revealed that platinum significantly improved the prognosis of these patients. 51 However, another study showed that patients with SMARCA4 alterations did not benefit significantly from chemotherapy.…”

“…To date, standard chemotherapy regimens for rhabdoid tumors have not been established. 4,17 However, surgery should be a vital part of the treatment, and R0 resection should be performed as much as possible. [52][53][54] Many targeted therapies for SWI/SNF complex-deficient tumors have emerged in recent years.…”

“…The expression of SMARCB1 is usually lost, whereas loss of SMARCA4 expression is rarely seen. 17 Proximal type epithelioid sarcomas are more common in the pelvis, perineum, and reproductive organs. SMARCB1 expression is completely absent in more than 90% of tumors, and CD34 staining is positive in about 50% of tumors.…”

“…Twelve patients with vimentin-positive gastric cancer with rhabdoid appearance by Utsunomiya et al were excluded because of the incomplete data. 13 The remaining 30 patients were described in 16 studies 1–3,7,14–25 (Table 2) and included 23 men and 7 women, aged 30 to 86 years old (average age: 64 years). Those older than 60 years accounted for two thirds of the study subjects.…”