Faculty Collaboration Database

Tumor profiling of gastric and esophageal carcinoma reveal different treatment options. Cancer Biol Ther 2015;16(5):764-9

Date

03/18/2015

Pubmed ID

25778705

Pubmed Central ID

PMC4622996

DOI

10.1080/15384047.2015.1026479

Scopus ID

2-s2.0-84943767513 (requires institutional sign-in at Scopus site)   19 Citations

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 = 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 HER2+ cohort (n = 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.

Author List

Miura JT, Xiu J, Thomas J, George B, Carron BR, Tsai S, Johnston FM, Turaga KK, Gamblin TC

Authors

Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin
Ben George MD Professor in the Medicine department at Medical College of Wisconsin
James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Cohort Studies
Esophageal Neoplasms
Female
Gene Expression Profiling
Genotype
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Middle Aged
Stomach Neoplasms