Diagnostic and Clinical Significance of the Special AT-Rich Sequence-Binding Protein 2 Deregulation in Gastrointestinal Malignancies.

INTRODUCTION

Gastrointestinal malignancies (GIs) - especially the colon adenocarcinoma (CAD) - represent the third leading cause of cancer-related morbidity and mortality, respectively. The development and progression of CAD is a multistep procedure in which a variety of deregulated molecules are implicated. Among them, the special AT-rich sequence-binding protein 2 (SATB2, gene locus: 2q33.1) seems to be a reliable marker for differential diagnosis and prognosis in patients suffering from GIs.

OBJECTIVE

The purpose of the current clinic-molecular review was to describe the role of the SATB2 protein in normal cell homeostasis and activity of epithelial cells and also to investigate the impact of its deregulation on GI and especially CAD patients.

MATERIAL AND METHOD: A systematic review of the literature was implemented based on the international PubMed database. Publications were evaluated at the basis of scientific importance and historical value regarding the SATB2 identification, nature, function and deregulation. The following keywords were used: SATB2, colon, carcinoma, transcription, DNA-binding. Fifty (n=50) important papers were selected for providing well-documented knowledge for the marker's behavior in non- and neoplastic disorders, also focused on GIs and CAD malignancies (CADs).

RESULTS

The majority of the examined original research studies reported a bi-phasic (overexpression/loss of expression) SATB2 protein pattern in GIs and specifically CADs. Additionally, they suggest that SATB2 should be a part of an immunohistochemical (IHC) panel - which also includes markers such as cytokeratins and transcriptional factors (caudal type homeobox 2-CDX2) - for implementing an accurate IHC-based diagnosis in primary and metastatic malignant tumors with GI origin.

CONCLUSIONS

SATB2 is a reliable and sensitive protein marker for differential diagnosis regarding GIs, including CADs. SATB2 gene silencing that leads to low or complete loss of its expression seems to be associated with an aggressive phenotype in CADs (advanced stage, increased metastatic potential, short survival rates).