Tumor profiling of gastric and esophageal carcinoma reveal different treatment options

Abstract

Background: NCCN states that chemotherapies for advanced esophageal and gastric cancers may be used interchangeably. Biomarkers from gastroesophageal cancer patients were interrogated to identify actionable alterations with therapeutic implications. Methods: 666 gastric and 640 esophageal cancer cases referred to Caris Life Sciences between 2009 thru 2013 were evaluated. Specific testing was performed, which included a combination of sequencing (Sanger, NGS) and protein expression (IHC). Results: In the complete cohort (n D 1306), 30 of 45 genes tested harbored mutations; highest rates were seen in TP53 (54%), APC (10%), SMAD4 (5.9%), KRAS (5.9%), and PIK3CA (5.1%). IHC of TOP2A was high in 76% of cases, TOPO1 in 51% and SPARC in 25%; low IHC of ERCC1 was seen in 65%, RRM1 in 62%, TS in 61% and MGMT in 45%, indicating potential benefit from epirubicin, irinotecan, nab-paclitaxel, platinum-based agents, gemcitabine, 5FU/capecitabine and temozolomide, respectively. In the HER2C cohort (n D 88), 50% of patients demonstrated possible benefit from a combination of trastuzumab with 5FU/capecitabine based on concurrent low TS, 53% with irinotecan (high TOPO1), 63% with cisplatin (low ERCC1) and 55% with gemcitabine (low RRM1). Subgroup analysis by tumor origin demonstrated significant differences in actionable biomarker profiles with HER2 (13% vs. 4.6%), SPARC (34% vs. 15%), TOP2A (86% vs. 67%), and TOPO1 (55% vs. 46%) in esophageal and gastric adenocarcinoma cases respectively (P < 0.05). Conclusion: A comprehensive multiplatform biomarker analysis suggested significant biomarker differences between gastric and esophageal cancers. These results can assist in the development of future clinical trials.

Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma

“…Moreover, overexpression of SPARC was correlated with a poor prognosis of patients with EAC [36]. Another study showed a significant difference in the SPARC levels in tumor tissue between gastric cancer and ESCC (15% vs. 34%) [37], suggesting SPARC as a potential novel therapeutic target. High expression levels of BGN have also been detected in a variety of human epithelial cancers [38,39], indicating a potentially important role in tumor development.…”

The design, analysis and application of mouse clinical trials in oncology drug development

“…Conflicting clinical trial reports exist regarding the role of ERCC1 expression in predicting cisplatin treatment on gastric cancer: some claimed that patients benefit more from low ERCC1 expression (De Dosso et al, 2013;Hirakawa et al, 2013;Kwon et al, 2007;Metzger et al, 1998;Miura et al, 2015), some stated the opposite (Baek et al, 2006;Bamias et al, 2010;Kim et al, 2011), while still others found no connection at all (Sonnenblick et al, 2012).…”

Relationships between <em>MGMT</em> promoter methylation and gastric cancer: a meta-analysis

“…Additionally, Miura et al indicated that negative expression of the MGMT gene was observed in 45% of the gastroesophageal tumors on the basis of biomarker profiling, suggesting potential sensitivity to temozolomide. 46 Therefore, it is necessary to detect the MGMT promoter methylation status in patients with gastric cancer to develop individualized treatment programs when they are treated with temozolomide.…”