ABSTRACT
It has been well established that the serial transplantation of an originally highly differentiated mammalian neoplasm leads regularly to a gradual loss of most or all visible expressions of histological differentiation within the tumour tissue. In a tumour that has undergone many years of serial transplantation there can usually be detected no resemblance to the tissue of origin, but rather a similarity to early embryonic tissue. Simultaneously with these morphological changes a gradual increase in growth rate takes place. The completely anaplastic tumour with a long transplantation history grows usually at a very rapid rate as compared to the original spontaneous tumour. The growth rate of such tumours is, however, still inferior to, or, at its maximum, equal to the growth rate of embryos of the same species (Schrek, 1936; Klein & Révész, 1953), but has never been found to exceed it. These changes in growth rate and level of differentiation are usually coincident with a gradual decrease in the number of histocompatibility factors the presence of which in the implanted host is necessary for the progressive growth of the tumour. This decrease has been interpreted as somatic mutation (Strong, 1926), antigenic simplification (Gorer, 1948), or, more recently, as immunological selection from among the antigenic variants in a population of malignant cells, where the antigenic variants arise mainly as a consequence of disturbances in chromosome number (Hauschka, 1952).
