ABSTRACT
AIMS: To evaluate the expression of αv-series integrins in brain metastases. Inhibitors targeting these integrins are being tested for their therapeutic potential. MATERIAL AND METHOD: The extracellular regions of the αvß3, αvß5, αvß6, αvß8, the cytoplasmic domain of ß3, the αv-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 αv-subunit was generally moderately to highly expressed in most tumors. αvß3 and cytoplasmic ß3 were weakly to moderately detectable in metastatic renal cell carcinomas and melanomas, αvß5 was prominently expressed in metastatic renal and colorectal carcinomas, αvß6 was most abundantly detectable in metastatic lung adenocarcinomas, but absent in melanomas. The tumor associated vessels in CNS metastases consistently expressed αvß3, αvß5, αv-, fibronectin and fibrinogen, however, mostly at low levels, while αvß6, αvß8 were lacking in vasculature. The comparative analysis of 38 matched primary tumors and brain metastases showed comparable levels of expression only for αvß3 and αvß8, while αvß6 and αvß5 were higher in primaries. CONCLUSION: We confirmed that integrin expression exhibits considerable heterogeneity according to tumor origin. αvß5 is the most promising target for integrin targeted treatment in brain metastases.
