Revising the Role of Integrin Subunit β4 Expression in Colon Cancer Progression and Survival

PURPOSE: Integrin subunit β4 (β4) has been proposed to play an important role in colon cancer progression through its involvement in hemidesmosome disassembly processes and tumor cell migration. However, the association between β4 expression and clinicopathological outcomes in colon cancer remains unclear. METHODS: Expression of β4 was assessed by immunohistochemistry in a large cohort of 651 colon cancer patients, the largest colon cancer cohort so far. Chi-squared tests were used to study the association between β4 expression and clinicopathological features. Overall and disease-free survival were assessed by Cox proportional hazard models. RESULTS: Loss of β4 expression was associated with local tumor invasion. Only 17.9% of the pT1 tumors displayed weak β4 expression level versus 28.1% of pT4 tumors, and 25.0% of the pT1 tumors had a high expression level versus 8.6% of the pT4 tumors (p = 0.012). No association between β4 expression and overall (p = 0.845) or disease-free survival (p = 0.767) was encountered, which disputes the role of β4 as a biomarker of malignant behavior in colon cancer. CONCLUSION: Contradictory reports have suggested opposite roles for β4 expression in (colon) cancer progression. In the present large cohort of colon cancer patients, we found that β4 expression was not associated with worse clinical prognosis, but decreased with advanced pathological tumor stage. Future studies should establish whether loss of β4 expression promotes invasive characteristics of colon cancer cells.