Major findings to emerge from this study are: in some patients with breast cancer, tumor and nontumor (stroma) environments express increased levels of TG2; in the stroma, TG2 protein exists in a catalytically active configuration, leading to cross-linking of the ECM proteins; and TG2-catalyzed cross-linking of ECM proteins may mitigate the migration of cancer cells to distant sites. This evidence concerns the gene TGM2 and breast cancer.