Clinicopathological characteristics and immune infiltration analysis of esophagogastric junction adenocarcinoma with alterations in SWI/SNF complex.

BACKGROUND: Alterations in SWI/SNF complex were mostly detected in poorly differentiated or undifferentiated gastric/esophagogastric junction adenocarcinoma (EGJA). However, there was a lack of studies investigating these alterations in a consecutive series of cases regardless of the morphology. Therefore, our study aimed to clarify the clinicopathological, prognostic, molecular and immune infiltration characteristics of a consecutive series cases with altered SWI/SNF complex in EGJA.

METHODS: We retrospectively analysed 266 patients who underwent surgery without neoadjuvant therapy. Tissue microarrays were constructed for evaluating molecular markers (INI1, ARID1A, BRM, BRG1, MLH1, PMS2, MSH2, MSH6, EGFR, c-MET, HER2, p53 and PD-L1) and immune cell markers (CD3, CD4, CD8, CD68 and CD163). Immune cell counts were quantified using Qupath.

RESULTS: Among the 266 patients, 36 (13.5 %) cases exhibited alterations in SWI/SNF complex. Specifically, 14 (5.3 %) cases were identified with ARID1A alteration, 21 (7.9 %) cases with BRG1 alteration, 7 (2.7 %) cases with altered BRM and 2 (0.8 %) cases with INI1 alteration. Alterations in ARID1A correlated with deficient mismatch repair (dMMR) (p < 0.001), increased CD3+T-cell (p = 0.017) and relatively increased CD8+ T-cell infiltration (p = 0.057), whereas alterations of BRG1 correlated with reduced CD3+T-cell infiltration(p = 0.036). There were no significant differences in clinicopathological or prognostic characteristics in EGJA patients with or without SWI/SNF or its subunits alterations.

CONCLUSION: Our findings indicate that the SWI/SNF complex demonstrates a notable frequency of alteration within the consecutive series of cases of EGJA. Alterations in ARID1A and BRG1 may correlate with distinct tumor microenvironment, which may provide new insights for optimizing treatment strategies in patients with SWI/SNF complex alterations.