Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus

• Published in: Human pathology 2008-03, Vol.39 (3), p.403-409
• Main Authors: Villanacci, Vincenzo, MD, Bellone, Graziella, PhD, Battaglia, Edda, MD, Rossi, Elisa, MD, Carbone, Anna, PhD, Prati, Adriana, PhD, Verna, Carlo, MD, Niola, Paolo, MD, Morelli, Antonio, MD, Grassini, Mario, MD, Bassotti, Gabrio, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Barrett Esophagus - metabolism; Barrett Esophagus - pathology; Barrett's esophagus; Biological and medical sciences; Cancer; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; DNA-Binding Proteins - biosynthesis; Dysplasia; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophagus; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Metaplasia; Middle Aged; Other diseases. Semiology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Proteins; Proto-Oncogene Proteins - biosynthesis; Signal transduction; Ski; SnoN; Transforming Growth Factor beta - metabolism
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2007.07.009

Summary Barrett's esophagus (BE) is a precancerous condition. However, the mechanisms underlying the transformation from metaplastic to dysplastic to adenocarcinomatous epithelium are still poorly understood. As loss of transforming growth factor- β growth inhibition is considered a hallmark of several human neoplasms, we evaluated the expression of Ski and SnoN (proteins that antagonize transforming growth factor- β signaling through physical interaction with Smad complex and by recruiting histone deacetylases), as markers of the transforming growth factor- β signaling pathway, in BE with and without dysplasia. Biopsy samples from 37 patients (26 men, aged 60 ± 8 years) with histologically proven BE were evaluated; 10 patients had concomitant low-grade dysplasia, 7 high-grade dysplasia (HGD), and 6 HGD associated with adenocarcinoma. Ski and SnoN expression was assessed immunohistochemically. Neither Ski nor SnoN was expressed in normal esophageal epithelium, but both were strongly expressed in BE tissue, with intense cytoplasmic positivity. Expression of these proteins decreased markedly in dysplastic areas in patients with low-grade dysplasia and was absent in those with HGD or HGD/adenocarcinoma. Ski and SnoN proteins are overexpressed in BE and may be involved in abnormal signaling elicited by transforming growth factor- β in this epithelium, enhancing the tumorigenesis process. These observations might help to elucidate the molecular mechanisms involved in the BE tumorigenesis process.