Clinical Implication of Serum Anti-p53 Antibodies and Overexpression of p53 Protein in Myelodysplastic Syndrome and Acute Myeloid Leukemia

Park, Joeng Seon; Park, Tae Hee; Park, Tae Seong; Jeong, Ju Seop; Lim, Young Tak; Lee, Eun Yup; Cho, Goon Jae

Abstract

BACKGROUND: Alteration of p53 genes is rare, but it is related with progressive diseases in hematologic malignancies. The wild type of p53 protein is not usually detected, but mutated p53 proteins are accumulated in the nuclei of tumor cells, which can be detected by immunohistochemical stain. Anti-p53 antibodies are found in the sera of patients with various malignant tumors as the result of immune response to accumulation of mutated p53 protein in tumor cells.
METHODS
The relation of serum anti-p53 anti-bodies and cellular p53 protein expression to clinical features in 36 cases of myelodysplastic syndrome (MDS) and 58 cases of acute myeloid leukemia (AML) was analyzed. Anti-p53 antibodies in the patient's sera were measured with enzyme immunoassay (p53 autoantibodies ELISA, Dianova, Hamburg, Germany). Immunohistochemical staining for p53 protein was performed with the streptavidin-biotin-peroxidase method (LSAB kit, DAKO, Denmark) and anti-p53 monoclonal antibody (DO-7, DAKO, Denmark) in paraffin embedded bone marrow biopsy sections.
RESULTS
Anti-p53 antibodies were positive in one of 36 (2.7%) MDS cases, and in four of 58 (6.8%) AML cases. Overexpression of p53 protein was seen in five (13.9%) of MDS and in five (8.6%) of AML. Serum p53 antibodies and p53 protein overexpression were more frequently found in RAEB, RAEB-t and M6 sutypes. There was no relation between anti-p53 antibodies and p53 protein overexpression in MDS and AML. The patients of MDS with anti-p53 antibodies and p53 overexpression tended to have severe dyserythropoiesis, higher Bounemouth scores and poor prognostic karyotypes and associated with shorter survival duration as compared to those without anti-p53 antibodies and p53 overexpression (4+/-1 vs 26+/-4 months, P=0.007). The patients of AML with anti-p53 antibodies and p53 protein overexpression tended to have poor prognostic karyotypes and resistance to chemotherapy.
CONCLUSION
Anti-p53 antibodies are rarely observed in sera of patients with MDS and AML, probably reflecting the relatively low incidence of p53 mutation. But the findings suggest that the presence of p53 alteration could be useful to predict resistance to chemotherapy and short survival in particular sutypes of MDS and AML.