Kun Jiang1,2, Kevin Neill1, Daniel Cowden1, Jason Klapman2,3, Steven Eschrich2,4, José Pimiento2,3, Mokenge P Malafa2,3, Domenico Coppola5,6,7. 1. Departments of Anatomic Pathology. 2. Oncological Sciences, University of South Florida, Tampa, FL. 3. Gastrointestinal Oncology. 4. Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute. 5. Departments of Pathology and Cell Biology. 6. Chemical Biology Molecular and Medicine. 7. Tumor Biology.
Abstract
BACKGROUND: Identifying the molecular switch responsible for the neoplastic progression of Barrett's esophagus (BE) and initiation of adenocarcinoma (ADC) 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 ADC; however, its expression in BE neoplasia has not been addressed. MATERIALS AND METHODS: We investigated the expression of the CAS/CSE1L protein immunohistochemically in 56 esophageal resection specimens for ADC arising in BE. For each specimen, a full representative section of the invasive 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 were evaluated using χ 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.
BACKGROUND: Identifying the molecular switch responsible for the neoplastic progression of Barrett's esophagus (BE) and initiation of adenocarcinoma (ADC) is clinically essential and it will have a profound impact on patient diagnosis, prognosis, and treatment. The cellular apoptosis susceptibility geneCAS/CSE1L is overexpressed in various cancers, including a rare report on esophageal ADC; however, its expression in BE neoplasia has not been addressed. MATERIALS AND METHODS: We investigated the expression of the CAS/CSE1L protein immunohistochemically in 56 esophageal resection specimens for ADC arising in BE. For each specimen, a full representative section of the invasive 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 humanCAS/CSE1L. Protein expression levels were measured using the Allred semiquantitative scoring system. The data were evaluated using χ 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.
Authors: Tanya Barrett; Dennis B Troup; Stephen E Wilhite; Pierre Ledoux; Dmitry Rudnev; Carlos Evangelista; Irene F Kim; Alexandra Soboleva; Maxim Tomashevsky; Kimberly A Marshall; Katherine H Phillippy; Patti M Sherman; Rolf N Muertter; Ron Edgar Journal: Nucleic Acids Res Date: 2008-10-21 Impact factor: 16.971
Authors: Amrita Salvi; Alexandria N Young; Andrew C Huntsman; Melissa R Pergande; Melissa A Korkmaz; Rathnayake A Rathnayake; Brittney K Mize; A Douglas Kinghorn; Xiaoli Zhang; Kiira Ratia; Markus Schirle; Jason R Thomas; Scott M Brittain; Claude Shelton; Leslie N Aldrich; Stephanie M Cologna; James R Fuchs; Joanna E Burdette Journal: Cell Death Dis Date: 2022-01-10 Impact factor: 8.469