Nuclear FOX M1 and Phophorylated β-Catenin S552 Expressions Are Observed in Barrett Dysplasia and Adenocarcinoma
Goo Lee, Megan M Kiefer, Daniella Posca, Bryan Rea, Lindsay Zak, Daniel Massi, William Blosky, Ben Bryant, Rana Abraham, Linheng Li, Jay Goldstein, Terrence A Berrett, Pradip Raychaudhuri, Grace Guzman. University of Illinois, Chicago, IL; Northwestern University, Chicago, IL; Stowers Institute, Kansas City, MO
Background: Diagnosis and surveillance of Barrett esophagus (BE), dysplasia and adenocarcinoma (AdC) remains challenging. Fox M1, a cell cycle regulator known to cross-talk with PI3K/Akt pathway, is expressed in many cancers. Phosphorylated-β-catenin S552 (P-β-cat S552), a marker for activated nuclear β-catenin phosphoryated at S552 and an indicator of PI3K/Akt-mediated β-catenin signaling, is up-regulated in PTEN-deficient intestinal polyp and colitis-associated cancer. Our aim was to evaluate the expression of these two proteins along with reported biomarkers of disease progression of BE namely: p16Ink4a (p16), β - catenin (β-cat), phosphorylated-histone-H3 (p-H-H3), and DNA mismatch repair proteins, in BE-dysplasia-AdC progression.
Design: Twenty endoscopic esophageal biopsies consisting of normal, BE, dysplasia and AdC (n=5 / group) were evaluated by immunohistochemistry for Fox M1, P-β-cat S552, p-H-H3, p16, β-cat, MLH1, MSH2, MSH6, and PMS2. Positively stained lesional nuclei were graded 0-3 for absent to strongest staining intensity.
Results: All samples were microsatellite-stable. FoxM1 showed increased (2 to 3) nuclear and cytoplasmic staining in dysplasia and AdC in comparison to no or weak (0 to 1) cytoplasmic staining in BE [figure A-D]. P-β-cat S552 [figure E-H] showed only nuclear staining and was markedly increased in dysplasia and AdC. Similar results were observed with p-H-H3 [figure I-L]. p16 showed increased nuclear and cytoplasmic staining in AdC [figure M-P]. β-cat showed 2 to 3 nuclear staining in dysplasia and AdC in comparison to membranous staining in BE [figure Q-T].
Conclusions: Here we show that nuclear expression of both Fox M1 and P-β-cat S552 is absent in normal/reactive and Barrett esophagus, noted as early as Barrett dysplasia, and persists in Barrett Adc. These results correlate with the findings seen in reported Barrett biomarkers including p16Ink4a (p16), β-catenin (β-cat), phosphorylated-histone-H3 (p-H-H3), and DNA mismatch repair proteins. The switch to nuclear expression of both Fox M1 and P-β-cat S552 in Barrett dysplasia and AdC suggests a possible role of PI3K/Akt signaling in Barrett disease progression.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 105, Monday Morning