Thymosin ß4 expression in colorectal polyps and adenomas

Abstract

OBJECTIVE:Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis.METHODS:In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry.RESULTS:Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells.CONCLUSIONS:Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown.

In Situ Characterization of Tissue-Resident Immune Cells by MALDI Mass Spectrometry Imaging

“…Moreover, the thymosin beta 4 gene is highly conserved in mammals and widely expressed in various tissues. Although there is no link between the expression of this gene and the differentiation of T cells, the protein is involved in various biological processes and was even described as playing a role in colon carcinogenesis and breast cancer . Today, the identification of peptides and proteins directly from a tissue is challenging.…”

MALDI-imaging reveals thymosin beta-4 as an independent prognostic marker for colorectal cancer

“…Additionally, it has been shown that Tβ-4 may drive the development of colorectal adenocarcinoma during multistage carcinogenesis [ 35 ]. TMA-based validation in this study confirmed these findings: while Tβ-4 immunoreactivity was absent or weak in normal mucosa, carcinomas showed moderate to strong immunoreactivity ( p = 0.0001).…”