Comparative Pathology: Li-Fraumeni Syndrome

P53 knock out mice of various types have been developed by mouse modelers. As might be expected the germline transmission results in tumors in multiple organs. The genesis of tumors is heavily dependent upon the activated oncogene. When bred to mice with activation of oncogenes such as cNeu or Myc, the tumors have the morphological appearance of the initiating oncogene but with a much more pronounced cytological dysplasia.  Note the difference in nuclear size.

                  Left: Tg(cNeu) tumor,                 Right: Tg(cNeuxp53-/-) tumor

 

When left to its own devices in the mouse, knock out of p53 frequently results in T cell lymphomas or spindle cell tumors of various organs. It has now been shown that many p53-related tumors are, in fact, EMT (Epithelial-Mesenchymal-Transition) tumors that originate in epithelium but transition under the influence of p53 mutation to spindle cell tumors.

This is one example of such a transition.  The initial tumor was induced in a Tg(Wnt) mouse and has the classical adenosquamous morphology of a Wnt- induced tumor but when the tumor recurred it became a spindle cell tumor and associated with p53 mutation. Note the EMT in the lower left and the adenosquamous in the upper right portion of the image.

Wnt tumor with EMT and adenosquamous differentiation (Mouse)

 

 

Click here to see the whole slide image.

Click here to view the human pathology.

 

Reference:

Gunther, E. J., S. E. Moody, et al. (2003). “Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis.” Genes Dev 17(4): 488-501.

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