Comparing the expression of integrins αvβ3, αvβ5, αvβ6, αvβ8, fibronectin and fibrinogen in human brain metastases and their corresponding primary tumors

Aims: To evaluate the expression of alpha v- series integrins in brain metastases. Inhibitors targeting these integrins are being tested for their therapeutic potential. Material and Method: The extracellular regions of the alpha v beta 3, alpha v beta 5, alpha v beta 6, alpha v beta 8, the cytoplasmic domain of beta 3, the alpha v- chain, and the ECM molecules fibronectin and fibrinogen were studied immunohistochemically in a series of 122 carcinoma and 60 melanomas metastatic to the central nervous system. In addition, 38 matched primary and metastatic tumors to the brain were compared directly. Results: The alpha v- subunit was generally moderately to highly expressed in most tumors. alpha v beta 3 and cytoplasmic beta 3 were weakly to moderately detectable in metastatic renal cell carcinomas and melanomas, alpha v beta 5 was prominently expressed in metastatic renal and colorectal carcinomas, alpha v beta 6 was most abundantly detectable in metastatic lung adenocarcinomas, but absent in melanomas. The tumor associated vessels in CNS metastases consistently expressed alpha v beta, alpha v beta 5, alpha v-, fibronectin and fibrinogen, however, mostly at low levels, while alpha v beta 6, alpha v beta 8 were lacking in vasculature. The comparative analysis of 38 matched primary tumors and brain metastases showed comparable levels of expression only for alpha v beta 3 and alpha v beta 8, while alpha v beta 6 and alpha v beta 5 were higher in primaries. Conclusion: We confirmed that integrin expression exhibits considerable heterogeneity according to tumor origin. alpha v beta 5 is the most promising target for integrin targeted treatment in brain metastases.