Could stroma contribute to field cancerization?

The common oral diseases as well as oral cancer have the characteristic of field cancerization or field effect. Field cancerization, characterized by phenotypic and genetic changes in the neighboring cells of the frank cancer cells, is a clinical phenomenon first found in head and neck cancers. Field cancerization of the epithelia is currently a widely-accepted model in cancer biology as a manifestation of cancer progression. The concomitant changes in the tumor microenvironment have drawn more attention recently. Could the changes in the tumor microenvironment and the epithelial field cancerization concepts be linked? In view of the importance of stroma in the development of epithelium and evidence in carcinoma-associated stroma, we propose the question if stroma not only reciprocates the neoplastic changes of the epithelia, but also contributes to field cancerization. Actually one perspective paper pointed out that healing wound can influence the recurrence of field cancerization. In another words, the microenvironment of healing wound determines the prognosis of field cancerization. Based on the literatures published and our own work, we hypothesize a new model of field cancerization focusing on the co-evolution of the tumor microenvironment. We suggest that the microenvironment cannot be neglected when treating diseases with characteristics of field cancerization.