Abstract
Simple SummaryThis study aimed to investigate the clinical relevance of immunohistochemical expression of proteins of the SWI/SNF complex, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in all patients and in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.
Highlights
Gastric cancer is ranked as the sixth-most-common cancer entity worldwide, having accounted for approximately 780,000 cancer-associated deaths in 2018 [1]
We evaluated the frequency, association with clinicopathological characteristics, and prognosis of alterations in SMARCA2, SMARCA4, SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 carcinomas of the stomach and gastroesophageal junction
The final cohort consisted of 477 patients with adenocarcinoma of the stomach or the gastroesophageal junction (Table 1)
Summary
Gastric cancer is ranked as the sixth-most-common cancer entity worldwide, having accounted for approximately 780,000 cancer-associated deaths in 2018 [1]. The best parameter for predicting prognosis and, therapy in gastric-cancer patients is TNM staging. The factors that are relevant for determining the prognosis of gastric carcinomas are local infiltration depth, locoregional lymph node involvement, distant metastases, and vascular invasion [2,3,4]. The introduction of perioperative chemotherapy after 2005 has improved the outcome in stage two and three gastric cancers, with a median survival of 50 months vs 34 months [8]. The prognosis of gastric cancer is still poor and has a five-year-survival rate that has not changed during the period between 2000 and 2014, with survival rates being between 31.4% and
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