—  SHORT COURSE  —

THE VALUE OF IMMUNOHISTOCHEMISTRY
IN THE ASSESSMENT OF BONE MARROW DISORDERS

Attilio Orazi, M.D., FRCPath. and Dennis P. O'Malley, M.D.




P53 OVEREXPRESSION BY IMMUNOHISTOCHEMISTRY

Loss of p53 function has a major role in the transformation process in hematologic malignancy, CML in particular . In a transgenic model of human CML, acquired loss of p53 has been shown to induces blastic transformation in p210-expressing hematopoietic cells. p53 alterations are also frequent in aggressive MDSs, particularly in therapy-related cases, and in secondary AML. The p53 gene product can be easily demonstrated in routinely processed bone marrow specimens. In our experience p53 overexpression is almost always associated with the presence of a complex karyotypes and poor prognosis.

Therefore p53 analysis of paraffin sections in MPDs and MDSs cases can be proposed as a "surrogate marker" for cytogenetics when the latter approach is not available.

References

  • Honda et al: Acquired loss of p53 induces blastic transformation in p210(bcr/abl)-expressing hematopoietic cells: a transgenic study for blast crisis of human CML. Blood. 2000; 95:1144-50.
  • Orazi et al: p53 overexpression in myeloid leukemic disorders is associated with increased apoptosis of hematopoietic marrow cells and ineffective hematopoiesis. Mod Pathol. 1996; 9:48-52.
  • Orazi A, Cattoretti G, Heerema NA, Sozzi G, John K, Neiman RS. Frequent p53 overexpression in therapy related myelodysplastic syndromes and acute myeloid leukemias: an immunohistochemical study of bone marrow biopsies. Mod Pathol 1993;6:521-5.
  • Orazi A, Cattoretti G, Soligo D, Luksch R, Lambertenghi-Deliliers G. Therapy-related myelodysplastic syndromes: FAB classification, bone marrow histology, and immunohistology in the prognostic assessment. Leukemia 1993;7:838-47.
  • Orazi A, Kahsai M, John K, Neiman RS. p53 overexpression in myeloid leukemic disorders is associated with increased apoptosis of hematopoietic marrow cells and ineffective hematopoiesis. Mod Pathol 1996;9:48-52.
  • Preudhomme et al: The clinical significance of mutations of the P53 tumour suppressor gene in haematological malignancies. Br J Haematol. 1997;98:502-11. Review.