SMAD7 and neoplasm: The high expression of TGFβ1 occurs in the invasive fronts of PTC, correlating with the loss of thyroid differentiation (38); and it is also observed in poorly circumscribed PTC that shows high levels of TGFβ in the tumor-periphery invasive front; on the other hand, in well-circumscribed PTC, the center of the (noninvasive) tumor shows inhibition of TGFβ signaling (high SMAD7 levels) (40).