Ets-1 and integrin beta3 for lung metastasis from colorectal cancer
Ets-1 functions as tissue-specific transcription factor and plays an important role in cell proliferation, differentiation, angiogenesis, and apoptosis. To elucidate the involvement of Ets-1 in lung metastasis from colorectal cancer, immunohistochemical analysis was performed on 51 colorectal cancer patients (22 with lung metastasis and 29 with advanced colorectal cancer showing no recurrence for at least 5 years after surgery). Tumorous and stromal Ets-1 immunoreactivity was evaluated. Ets-1 protein was demonstrated within stromal fibroblasts, myofibroblasts and capillaries, and also within carcinoma cells. Stromal Ets-1 immunoreactivity in primary colorectal cancer was statistically correlated with lung metastasis (p<0.05). In primary colorectal cancer, a significant association was observed between stromal Ets-1 immunoreactivity and vascular integrin beta3 expression (p<0.01). In the cases with lung metastasis, vascular integrin beta3 index in lung metastases was significantly diminished compared with primary tumors or liver metastases (p<0.01). In contrast, stromal or tumorous Ets-1 expression did not change. In a multivariate model using logistic stepwise regression analysis, vascular integrin beta3 and stromal Ets-1 overexpression were significantly and independently related to lung metastasis. Stromal Ets-1 and/or vascular integrin beta3 may be useful markers for risk of lung metastasis from colorectal cancer.