The ontogenetic cancer field model of locoregional tumor spread
The development of organisms from the fertilized oocyte (ontogenesis) proceeds with trajectories of successive bifurcations making up the pathways for the different cell types (cell lineage specification, cell fate progression). Complex epigenetic processes generate temporarily stable global chromatin structures that determine form and function of the corresponding cell type at the intermediate and terminal stages.
Each step in fate progression increases the morphological and functional complexity of the cell type at the cost of its plasticity concomitant with reduced positional potential. The tissue domains permissive for a distinct cell type become more and more specified.
Before determination, cells comprise the expanding habitats of multiple cell types whose stem cells can transdifferentiate into each other. Populations of determined cell types are confined to topographically defined compartments further segregating into subcompartments and finally zones of the mature organism.
The cancer field model considers cancer progression as pathological fate regression of transformed stem cells in the mature organism with a competent adaptive immune system. The tissues for potential local tumor progression, the cancer fields, represent the mature derivatives of the founder tissue domains in reverse sequence. Thus, an order of cancer is established. The topologic relationship between the local tumor extent and the mature tissues of sequential developmental steps determines the ontogenetic tumor stage (oT).
The regional lymph nodes executing peripheral immune tolerance for their tributary tissues provide additional permissive sites for discontinuous tumor spread, especially for epithelial neoplasms.
The ontogenetic cancer field model for regional progression of carcinomas assumes that memory Treg cells and memory Breg cells against peripheral antigens of the normal tributary tissue in the draining lymph node provide a proliferation matrix for tumor cells with similar antigens. Since the lymph nodes are invariably connected to their tributary regions through afferent lymphatics and exhibit common tissue antigens, the potential regional propagation field can be identified for each local cancer field of the individual neoplasm.
Considering the ontogenesis of the lymphatic system and secondary lymphoid tissue / lymph nodes allows the topographic identification of first-, second- and third-line lymph nodes with corresponding potential for metastases formation for any local cancer field and thus to establish an ontogenetic nodal staging system as well.
