Two-dimensional protein electrophoresis and the identification of histologically indeterminate human cancers

It is proposed to identify histologically indeterminate human cancers by comparing their qualitative content of stained proteins, separated by two-dimensional electrophoresis, with patterns of proteins from a series of identified human cancers of comparable or different stem cell origin. The hypothesis to be tested is that in cancer, biochemical ontogeny, reflected in the distribution of cellular and tissue proteins, will recapitulate phylogeny, albeit in a manner less organized than normal. Patterns of protein from cancer cells, whether histologically identified or not but originating from embryologically similar stem cells, are expected to exhibit greater homology, compared with protein profiles of cancer cells derived from stem cells of different embryologic origin. Normal or cancer cell proteins common or unique to one or more cell sources can be identified, and subsets of proteins that characterize cancer cells of specific stem cell origin identified. There are reasons to believe that cancer cells rarely, if ever express properties inconsistent with the basic cellular commitment of their stem cell of origin. Photo-optical scanning and computer-assisted analysis will greatly facilitate collating the many hundreds of discrete proteins, among which those used to characterize different cancer cells are to be found.