Switch/Sucrose-non-fermentable（Swi/Snf）复合物（ARID1A、SMARCA2、SMARCA4）缺陷型子宫颈内膜腺癌的临床病理特征

Subunits of the Switch/Sucrose-non-fermentable (Swi/Snf) complex, such as ARID1A, SMARCA4, SMARCA2, etc., have been implicated in the development of gynecologic cancers. However, their prevalence and clinical implications in endocervical adenocarcinoma (ECA) remain unclear. This study aimed to evaluate the expression of Swi/Snf complex subunits in ECA and characterize the clinicopathological and immune microenvironment features of Swi/Snf-deficient ECA.

We evaluated 604 ECA using representative tissue microarrays, collected clinicopathologic data, reviewed histological features, and performed immunohistochemical staining for several Swi/Snf complex subunits, mismatch repair (MMR), immune cell markers, and immune checkpoint ligands proteins.

Among the 604 cases examined, five Swi/Snf subunit expression patterns were identified, including intact expression, deficient expression, 'checkerboard' expression, reduced expression, and heterogeneous expression. Deficiencies of ARID1A (3.97%, 24/604), SMARCA2 (2.32%,14/604), and SMARCA4 (1.49%, 9/604) were observed. Defining Swi/Snf deficiency as loss of any subunit, the overall deficiency rate was 5.96% (36/604). Swi/Snf-deficient ECA tended to advanced FIGO stage (III-IV, P = 0.041), larger tumor size (P < 0.001), deeper stromal invasion (≥ 1/3, P = 0.046), and higher lymph node metastasis rate (P = 0.037). Morphologically, Swi/Snf-deficient ECA displayed frequent poor differentiation (P = 0.001), medullary features (P < 0.001), high nuclear grade (P < 0.001), necrosis (P = 0.001), stromal tumor-infiltrating lymphocytes (sTILs, P < 0.001), peritumoral lymphocyte aggregation (P = 0.001), and tertiary lymphoid structures (TLS, P < 0.001). Immune subset analysis revealed significantly elevated densities of CD3⁺ T cells, CD8⁺ T cells, CD38⁺ plasma cells, CD56⁺ NK cells, CD68⁺ macrophages, and PD-1⁺ T cells in Swi/Snf-deficient ECA (P < 0.05). Swi/Snf-deficient ECA demonstrated higher PD-L1 combined positive score (CPS) positivity (P < 0.001), and was more frequently associated with mismatch repair deficiency (MMRD, P < 0.001). Survival analysis indicated shorter overall survival (median: 53 vs. 64.5 months, P = 0.0307) and disease-free survival (median: 52 vs. 60.5 months, P = 0.0228) in Swi/Snf-deficient ECA patients.

Swi/Snf complex deficiency is rare but significantly associated with NHPVA, aggressive pathological features, immunologically activated phenotypes, and MMRD. Swi/Snf status evaluation may inform novel therapeutic strategies for ECA patients.