Stromal cell derived factor-1 and CXCR4 expression in colorectal cancer promote liver metastasis.

BACKGROUND: Recent studies suggest that SDF-1 and CXCR4 are expressed in certain cancer cells, and malignant cells use this chemokine/receptor system to promote tumor progression and metastasis. However, the pathophysiological significance of their expression in colorectal cancer (CRC) tissue has not been fully elucidated. OBJECTIVE: The purpose of this study was to assess SDF-1/CXCR4 expression and to explore its contribution to colorectal cancer. METHODS: We examined SDF-1 and CXCR4 mRNA expression in 124 primary colorectal tumour and 35 liver metastases tissues and matched adjacent noncancerous tissues by reverse transcriptase PCR (RT-PCR). Furthermore, their expression was analyzed by immunohistochemistry. The relationship between SDF-1/CXCR4 expression and clinicopathological features were analyzed by appropriate statistics. X2 test and Kaplan-Meier analysis were used to investigate the correlation between the ligand-receptor expression and prognosis of colorectal cancer patients. RESULTS: The relative mRNA expression of SDF-1 and CXCR4 was significantly elevated in colorectal cancer tissues as compared with adjacent noncancerous tissues (P < 0.001). The high expression of proteins expression in colorectal cancer tissues was significantly correlated with tumor grade (P = 0.0001), clinical stage (P < 0.05), and lymphatic invasion (P < 0.05). Furthermore, patients with CXCR4 nuclear-type expression showed more frequent lymph node metastasis (p = 0.021), advanced clinical stage (p = 0.001) and lymphatic invasion (p = 0.03) than those with cytoplasm staining-type. Kaplan-Meier survival analysis revealed that high expression of the couple SDF-1/CXCR4 correlated with poor prognosis of colorectal cancer patients (P < 0.001). CONCLUSION: SDF-1 and CXCR4 may play an important role in the progression of colorectal cancer. The present data suggest that there is a significant association between SDF-1/CXCR4 to enhance the liver metastases causing poor prognosis. Those proteins may potentially be used as an independent biomarker for the prognostic evaluation of colon cancer in the Tunisian cohort.

Relationship between SDF-1G801A polymorphism and its expression in Tunisian patients with colorectal cancer.

The aim was to evaluate the relationship between SDF-1G801A polymorphism and its immunohistochemical expression in colorectal cancer tissues in the Tunisian cohort. The molecular and immunohistochemical analysis showed that SDF-1G801A polymorphic variant was higher in CRC patients with TNM stage II and III, the SDF-1 expression was significantly increased from normal mucosa to primary tumor (p < 0.05). CRC patients have higher frequency of A allele (52.01%) than controls (26.8%) (P = 0.0001). Thus, SDF-1 polymorphism is a risk factor of colorectal cancer susceptibility in our population, the polymorph genotype of SDF-1 maybe associated with clinical manifestations in CRC patients in Tunisia.

The prognostic value of the immunohistochemical expression and mutational pattern of the key mediator of Wnt signaling: beta-catenin in Tunisian patients with colorectal carcinoma.

Beta-catenin plays a critical role with E-cadherin in cell-cell adhesion and is also a key molecule of the highly conserved Wnt signaling pathway that regulates cell proliferation and differentiation. Abrogation of this pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer. The objective of this study was to determine the prognostic value of ß-catenin/E-cadherin complex in Tunisian patients with colorectal cancer. Matched primary tumors from 150 patients with sporadic colorectal adenocarcinomas were stained for ß-catenin and E-cadherin by using immunohistochemistry. Deletion of exon 3 of CTNNB1 gene was performed by polymerase chain reaction. Our results showed that ß-catenin and E-cadherin expressions were related inversely to tumor differentiation. Furthermore, the nuclear expression of ß-catenin was considerably increased in advanced colorectal adenocarcinomas and was highly associated with shorter survival of patients. Deletion of exon 3 of CTNNB1 was identified in 2 cases by using polymerase chain reaction and was significantly related to tumor invasion and aberrant expression of E-cadherin. The major finding of this study is that activation of ß-catenin gene by deletions involving exon 3 may be considered as an advanced event in colorectal tumorigenesis in Tunisian patients, in contrast to some worldwide studies. Moreover, disruption of ß-catenin/E-cadherin complex may be considered as a dependent predictor of disease outcome.

Relationship between expression of ras p21 oncoprotein and mutation status of the K-ras gene in sporadic colorectal cancer patients in Tunisia.

INTRODUCTION: The K-ras proto-oncogene encodes a protein (p21-ras) belonging to the family of GTP/GDP-binding proteins with GTPase activity. The activation of ras family genes plays an important role in colorectal tumorigenesis. Frequency of K-ras mutations and overexpression of the protein in colorectal cancer (CRC) vary between 14% and 50% and between 29% and 76%, respectively. AIMS: We investigated the clinicopathologic characteristics of patients with CRC and their relationship with point mutations of K-ras oncogene codons 12/13 and ras p21 expression. MATERIALS AND METHODS: K-ras codons 12 and 13 point mutations were examined by direct sequence analysis, whereas the ras p21 expression was evaluated using immunohistochemistry. RESULTS: Statistical analysis of immunohistochemical results showed that the expression of ras p21 was correlated with the advanced age of patients (P=0.0001), whereas loss of signal was associated with mucinous histotype (P=0.0001). Mutations in the K-ras gene were detected in 12 of the patients with CRC. Mutations in K-ras gene were found in 12 of 52 tumors (23.07%), and 7 mutations were G→A transitions (58.33% of all mutations), 4 were G→T transversions (33.33%), and only 1 was G→C transversion (8.33%). A total of 83.33% of the mutation occurred at codon 12 and 16.67% at codon 13. Moreover, K-ras mutations were associated with the sex of patients (P=0.017). CONCLUSIONS: Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC.

[Epidemiological study, pathologic evaluation and prognostic factors of colorectal mucinous vs non-mucinous adenocarcinoma (a series of 196 patients)]. / Etude épidémiologique, anatomopathologique et évaluation des facteurs pronostiques des adénocarcinomes colorectaux mucineux vs non mucineux. (A propos d'une série de 196 patients).

BACKGROUND: Colorectal carcinoma is one of the main causes of cancer death in the worldwide with a decrease survival rate in relationship with a later diagnosis of advanced disease. AIMS: This study highlights the particular epidemiological, clinicopathological and immunohistochemical colorectal cancer profile. Indeed, our results differ markedly from that reported in the literature. METHODS: We underwent a retro and prospective study interesting 196 patients with colorectal carcinoma diagnosed in the pathological and cytological laboratory of Mongi Slim Hospital (Tunisia). Age at diagnosis, mode of presentation, sex, tumour location, macroscopic and histological features, TNM and Astler Coller stage were assessed and evaluated. RESULTS: We report here a particular epidemiological pattern which is characterised by younger age of the patients, equally distribution between men and women, predominant sporadic carcinomas and preponderance of rectosigmoid location. The poorer degree of differentiation and mucinous subtype are correlated with an advanced stage. It is also correlated with more frequent vascular embols, neural invasion and metastatic nodes. Furthermore, immunohistochemical analysis of galectin-3 showed a significant difference between mucinous and non mucinous adenocarcinoma. CONCLUSION: Based on the presented data, the epidemiological pattern and the anatomic distribution especially in the rectosigmoid region suggest diet and lifestyle to be primordial risk factors of colorectal tumorigenesis.