Expression of CAS/CSE1L, the cellular apoptosis susceptibility protein, correlates with neoplastic progression in Barrett’s esophagus

BACKGROUND: Identifying the molecular switch responsible for the neoplastic progression of Barrett’s esophagus (BE) and initiation of adenocarcinoma is clinically essential and it will have a profound impact on patient diagnosis, prognosis, and treatment. The cellular apoptosis susceptibility gene CAS/CSE1L is overexpressed in various cancers, including a rare report on esophageal adenocarcinoma; however, its expression in BE neoplasia has not been addressed. METHODS: We investigated the expression of the CAS/CSE1L protein immunohistochemically in 56 esophageal resection specimens for adenocarcinoma arising in BE. For each specimen, a full representative section of the invasive adenocarcinoma (ADC) was selected to include, when possible, BE, low grade dysplasia (LGD) and high grade dysplasia (HGD). Samples were stained for CAS/CSE1L expression using a rabbit polyclonal antibody recognizing the N-terminus of human CAS/CSE1L. Protein expression levels were measured using the Allred semiquantitative scoring system. The data was evaluated using chi-squared statistical analysis. Gene expression Omnibus was queried for CAS/CSE1L and BE neoplasia. RESULTS: We found minimal to absent CAS/CSE1L in all BE tissue samples; however, CAS/CSE1L was upregulated in 60% of LGD and overexpressed in HGD and ADC. The results were statistically significant (P< 0.05). The localization of CAS/CSE1L protein was nuclear in BE; it became nuclear and cytoplasmic in LGD and HGD, and predominantly cytoplasmic in ADC. A similar progressive increase was observed for CAS/CSE1L gene expression. CONCLUSION: These findings show changes in CAS/CSE1L during BE progression. CAS/CSE1L may represent a potential marker for dysplasia/carcinoma.