Abstract
Abstract only
249
Background: Since 1975, Esophageal adenocarcinoma (EAC) incidence has increased more than any other cancer (̃700%). Pre-malignant metaplastic tissue, or Barrett's Esophagus (BE), is the only known precursor for EAC. Periodic histological assessment of endoscopic biopsy along dysplasia-carcinoma sequence is used to assess progression risk. Current surveillance protocols have clinical limitations as 80% of patients still present with stage II-IV EAC. The aim of this study is to compare novel proteomic expression patterns to distinguish stable BE patients from those who developed EAC using the STLA101 assay. Methods: After Institutional Review Board approval patients with BE/GERD were identified. Two cohorts were selected: progressors (progressed to EAC at subsequent interval of 0.5-3 years) and non–progressors (̃10 yrs of f/u surveillance without progression along dysplasia/carcinoma path). 24 normal esophageal mucosa samples with no h/o of BE were also retrieved for baseline expression levels. Tissue sections were microdissected to isolate pure BE cells from surrounding stromal cells. BE cells underwent a multi-step process where tissue was heated and digested to produce a liquid biopsy for mass spec. Isotopically labeled control peptides representing the STLA101 panel were spiked in with digested tissue samples to quantify all of the markers simultaneously using a Triple-quad mass spectrometer. Results: A total of 95 tissues were analyzed. 29 BE biopsies progressed to EAC within a mean of 380 days while the remaining 28 BE and 14 GERD specimens did not progress over a 10-yr period. All 8 biomarkers were expressed at a higher level in BE tissue that progressed to cancer when compared to BE/GERD tissue that remained stable over 10 years. The assay had a 100% technical success rate as no samples yielded “non-detectable” data points. Conclusions: The differential overexpression of the STLA101 panel on progressive and non-progressive BE tissues demonstrates the clinical utility of STLA101 as a predictive biomarker panel for early detection of esophageal carcinogenesis. Non-progressive BE tissues were similar to normal mucosa, therefore, patients whose BE tissue samples resemble this profile may receive a reduced screening cadence. On the other hand, patients with overexpression of the STLA101 panel may be eligible to receive more frequent screening or therapeutic intervention.