What is sign for progressive of colorectal carcinoma?
The process of tumor invasion and metastasis is associated with alterations in the functions of several adhesion molecules. In general, tumor cells lose their capacity for normal adherence, which facilitates their detachment from their site of origin. alpha-catenin links E-cadherin to the actin cytoskeleton via its association with either beta- or gamma-catenin. Reduced alpha-catenin expression was associated with tumor invasion and metastases in colorectal cancer (CRC).
A research article to be published on August 21, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Adam Elzagheid from University of Turku of Finland examined alpha-catenin expression in a series of 91 patients with advanced colorectal carcinoma, and analyzed the relationship with clinical and pathological features of colorectal cancer patients.
Archival tumor samples were analyzed using immunohistochemistry (IHC) for alpha-catenin in 91 patients with advanced colorectal cancer. Patients with high alpha-catenin expression (MI, CI) had a significantly increased lymph node metastasis. There is also significant difference in alpha-catenin expression between tumors of the proximal and distal sites. Interestingly, alpha-catenin expression (MI) was more intense in carcinomas of the descending colon and rectum as compared with the lesions localized in the ascending and transverse colon. Similar observation was reported for beta-catenin, but not for alpha-catenin.
There is increasing evidence to suggest that molecular mechanisms and molecular phenotypes differ in carcinomas arising in the proximal and distal segments of the large bowel. The involvement of different molecular pathways in colorectal carcinogenesis is exemplified by the fact that cancers of "mutator" phenotypes preferentially occur in the proximal colon, whereas the adenoma-to-carcinoma sequence phenotype is characteristic of carcinomas in the distal colon and rectum. Corresponding differences have also been demonstrated with other potential prognosticators. To our knowledge, this is the first study to investigate the relation between alpha-catenin expression and response to treatment. Interestingly, a significant relation was observed between CI and the response to treatment. Accordingly, the patients with low CI were more responsive to treatment than patients with high CI values. The significance of these observations remains to be elucidated in a larger study, however.
The manuscript is well written and the results implicate that high alpha-catenin expression is associated with invasive phenotype, lymph node metastases, and progressive disease in colorectal cancer. It includes interesting new data of alpha-catenin expression in colon carcinomas of different locations. This is also the first study to investigate the relation between alpha-catenin expression and the response to treatment.