Korean J Hematol 2001; 36(1):
Published online March 31, 2001
© The Korean Society of Hematology
박정선, 박태희, 박태성, 정주섭, 임영탁, 이은엽, 조군제
부산대학교 의과대학 임상병리학교실,
부산대학교 의과대학 내과학교실,
부산대학교 의과대학 소아과학교실
Background: Alteration of p53 genes is rare, but is 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 immunohisto-chemical 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 antibodies 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.
Keywords Anti-p53 antibodies; p53 protein; Myelodysplastic syndrome; Acute myeloid leukemia;
Korean J Hematol 2001; 36(1): 1-8
Published online March 31, 2001
Copyright © The Korean Society of Hematology.
박정선, 박태희, 박태성, 정주섭, 임영탁, 이은엽, 조군제
부산대학교 의과대학 임상병리학교실,
부산대학교 의과대학 내과학교실,
부산대학교 의과대학 소아과학교실
Joeng Seon Park,Tae Hee Park, Tae Seong Park, Ju Seop Jeong, Young Tak Lim, Eun Yup Lee, Goon Jae Cho
Department of Clinical Pathology, Internal Medicine and Pediatrics Pusan National University, College of Medicine, Pusan, Korea
Background: Alteration of p53 genes is rare, but is 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 immunohisto-chemical 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 antibodies 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.
Keywords: Anti-p53 antibodies, p53 protein, Myelodysplastic syndrome, Acute myeloid leukemia,