[Clinicopathological analysis of SMARCA4-deficient tumors of digestive system origin].

Objective: To analyze the clinicopathological characteristics, treatment, and prognosis of SMARCA4-deficient tumors of digestive system origin, and to deepen the understanding of this tumor subtype. Methods: A retrospective analysis was conducted on 18 patients diagnosed with SMARCA4-deficient tumors of digestive system origin at Tianjin Medical University Cancer Institute and Hospital from January 1, 2021 to December 31, 2024. Their clinicopathological features, treatments, and prognoses were summarized. Immunohistochemical staining was used to detect BRG1.

Using solid tumor data from the MSK-CHORD cohort (25 040 samples from 24 950 patients) and the MSK-IMPACT cohort (54 331 samples from 48 179 patients) in the public database cBioPortal, survival analysis and gene mutation profiling were performed focusing on SMARCA4 gene alterations. Results: The 18 SMARCA4-deficient tumors included 10 gastric cancers, 4 gallbladder/bile duct cancers, 2 liver cancers, and 2 colorectal cancers. The mean age of the patients was 62.8 years; there were 14 males and 4 females. Seven patients were initially diagnosed with advanced-stage disease, of whom 5 had metastases to ≥2 distant organs. Based on cytomorphology and immunohistochemistry (IHC) results, 8 cases were classified as undifferentiated carcinoma, 2 as poorly differentiated carcinoma, 5 as poorly differentiated adenocarcinoma, 1 as neuroendocrine carcinoma and 2 as undifferentiated sarcomas.

Among the 18 patients, 16 had a Ki-67 index>50%, and high expression levels were observed for INI1 (14/14) and Syn (12/15). Regarding survival, 5 patients had an overall survival (OS) of