Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer

Abstract

Objective: Since colorectal cancers (CRC) are tumors with heterogeneous biological behavior, prediction of their prognosis remains challenging. Caudal-related homeobox gene 2 (CDX2), which has important roles in the development and maintenance of intestines, is thought to have tumor suppressing effect on CRCs. The aim of this study was to investigate the prognostic significance of decreased-CDX2 expression. Method: This retrospective study included 224 patients diagnosed with CRC between 2009 and 2014. Paraffinized blocks of these patients were stained with CDX2 immunohistochemically and evaluated semiquantitatively. Results: Only 35 (15.6%) of 224 patients had low-CDX2 expression. Decrease in CDX2 expression was closely associated with classical prognostic parameters such as histopathologic type, histologic grade, lymph node metastasis, distant metastasis, and TNM stage. Patients with decreased-CDX2 expression had more lymph node metastasis (p=0.013) and advanced TNM stage (p=0.004) than those without decreased-expression. The mean survival was 53.0±0.89 months. Cox regression analysis showed that decreased-CDX2 expression was significantly related with overall survival (Univariate analysis; hazard ratio: 0.

Correlation of CDX2 Protein Expression with Clinicopathologic Features and Survival Rate in Iraqi Patients with Colorectal Cancer

“…Similarly, other studies observed low CDX2 expression is significantly correlated with poor differentiation grade. Besides, other studies found the same result regarding the association between low expression of this protein and high grade of CRC (Bonetti et al 2017;Çalik et al 2020;Dalerba et al 2016;Oslen et al 2014;Shigematsu et al 2018). On the contrary, the current result was in disagreement with that reported by (Hong et al 2013;Sjoerd et al 2021).…”

“…Downregulation of CDX2 expression has been correlated with CRC progression, and the results of various studies suggest this gene may have tumor suppressor activity, though the extent to which this activity correlates with prognosis, patient survival, and clinicopathologic characteristics is still debatable (Cecchini et al 2019;Xu et al 2019). Previous researches have demonstrated that a low CDX2 expression is associated with a worse prognosis and shorter survival in CRC patients (Çalik et al 2020;Zheng et al 2017). Therefore, the purpose of this study was to determine whether or not CDX2 expression was associated with better outcomes for people with CRC.…”

Evaluation of the Immunohistochemical Scoring System of CDX2 Expression as a Prognostic Biomarker in Colon Cancer

“…In multiple instances, researchers have demonstrated that diminished or absent CDX2 expression is associated with the aggressive behavior of CRC, characterized by invasive and poorly differentiated tumors, as well as low overall survival (OS) and disease-free progression (DFS) rates [7,9,21,31,34,[36][37][38].…”

“…Although researchers have shown that there is no statistically significant correlation between the age and sex of patients and tumors exhibiting reduced or absent CDX2 gene expression, some studies have suggested a greater prevalence of CDX2-negative tumors in elderly women [34,36,37,39,40]. Concerning the primary tumor site, research suggests that tumors exhibiting diminished or negative CDX2 expression are commonly found in the right colon, including the cecum, ascending colon, and transverse colon [9,32,34,40,41].…”

“…The CDX2 protein demonstrates robust nuclear expression within non-neoplastic intestinal epithelial cells and is reliably identified in the vast majority of CRC histological subtypes (90-100%), including metastases originating from colorectal tissue, thereby functioning as an immunohistochemical marker for confirming or excluding intestinal origin in secondary tumors of unknown origin [9,31,34,36,40]. However, in 10-30% of CRC cases, a reduced or negative CDX2 expression has been observed [7,37,40,49]. The CDX2 protein, while commonly associated with colorectal tumor cells, exhibits expression in various tumors of the digestive system, including duodenal (100%), gastric (71%), and pancreatic (30%) tumors, and may additionally be detected in neuroendocrine tumors and mucin-producing malignancies like bladder, ovarian, pulmonary, and biliary carcinomas [9,34,39].…”