Role of β4 integrin in HER-3-negative, K-RAS wild-type metastatic colorectal tumors receiving cetuximab.

AIMS: Altered α6β4 integrin expression has been demonstrated in HER-3-negative tumors and may be responsible for anti-HER treatment resistance. The current study aimed to evaluate the interaction between polymorphisms of α6 and β4 integrins and clinical outcome in HER-3-negative, K-RAS wild-type colorectal cancer patients receiving cetuximab. PATIENTS & METHODS: K-RAS analysis was performed via direct sequencing, HER-3 was evaluated by immunohistochemistry and genotyping of α6 and β4 integrins was performed by real-time PCR. RESULTS: An univariate analysis, the β4 rs8669, rs871443 and rs9367 polymorphisms correlated with progression-free and overall survival. On multivariate analysis, only the β4 rs8669 maintained an independent role in influencing progression-free survival. CONCLUSION: We believe that β4 rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment. Our findings could also be relevant in planning future trials testing treatment strategies against the integrin-activated molecular pathways.