HIGH P53 PROTEIN EXPRESSION IS ASSOCIATED WITH WT1 MRNA LEVEL AND DISEASE STAGE PROGRESSION IN PATIENTS WITH MYELODYSPLASTIC SYNDROME.
(Abstract release date: 05/21/15)
EHA Library. Yamazaki E. 06/12/15; 102632; PB1827
Disclosure(s): Yokohama City University HospitalClinical Laboratory Department
Dr. Etsuko Yamazaki
Contributions
Contributions
Abstract
Abstract: PB1827
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) is a heterogeneous disease. Several clinical findings were reported as prognostic markers. Identification of p53-positive cells by immunohistochemistry in bone marrow (BM) was demonstrated to correlate with presence of TP53 mutations, indicative of poor prognosis. Wilms’ tumor gene (WT1) mRNA expression was associated with the WHO classifications and risk evaluation of MDS. But there was no report about correlation between p53 expression and WT1 mRNA level.
Aims
We assessed BM biopsy specimens for p53 expression by immunohistochemistry in association with other clinical parameters including WT1 mRNA expression in adult MDS patients.
Methods
We performed a retrospective study involving 29 BM biopsy samples from 24 patients with MDS between 2013 and 2014. The percentage of p53 staining positive cells was assessed based on a total manual count of 1000 BM hematopoietic cells. Clinical parameters were corrected from patient medical charts .
Results
The study included 17 males and 7 females. The median age at procedure was 71 years (range, 28-84). Five patients received sequential BM biopsies when clinical findings changed. According to WHO 2008 classification of MDS, 14 specimens were RCMD, 3 were RCMD-RS, 6 were RAEB-1 and 6 were RAEB-2. The result of cytogenetic analysis of 26 samples, showed complex karyotypes with more than 3 abnormalities found in 7 samples including 4 of complex karyotype with -5/5q-, isolated del5q was not found in this cohort and 11 were normal karyotype. Nine patients (11 specimens) were treated with azacitidine after first biopsy. With the median post-procedure follow up of 5.7 months (1-23.3 months), leukemic transformation and death occurred in one patient (two specimens) and two patients (three specimens), respectively. Positive rate of p53 expression in BM was as follows; <1%, 5 specimens; 1-3%, 8; 3-5%, 4; 5-10%, 4; >10%, 8. In 5 patients with sequential biopsies, p53 expression level of first sample was lower than it of second sample except in one patient who received azacitidine treatment after first biopsy. WT1 mRNA expression level in peripheral blood (PB) was as follows; <100 copies, 11; 101-1000copies, 8; >1000 copies, 6; 4 patients were not tested for WT1 mRNA level at the time of BM biopsy. Higher level of p53 expression was significantly associated with greater WT1 mRNA expression level in PB (r = 0.40, P = 0.05), complex cytogenetic abnormality (r = 0.64, P < 0.001), increasing with WHO2008 classification (r = 0.68, P < 0.001), IPSS (r = 0.50, P = 0.01), and IPSS-R (r = 0.53, P = 0.006). But it was not associated with percentage of CD34 positive cells in BM. In spite of short duration of follow-up time, high level of p53 expression was associated with overall survival (r = 0.54, P = 0.003).
Summary
High p53 protein expression in BM is associated with WT1 mRNA expression level and disease stage progression. It can be a predictor of survival in adult MDS.
Keyword(s): P53, WT1
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) is a heterogeneous disease. Several clinical findings were reported as prognostic markers. Identification of p53-positive cells by immunohistochemistry in bone marrow (BM) was demonstrated to correlate with presence of TP53 mutations, indicative of poor prognosis. Wilms’ tumor gene (WT1) mRNA expression was associated with the WHO classifications and risk evaluation of MDS. But there was no report about correlation between p53 expression and WT1 mRNA level.
Aims
We assessed BM biopsy specimens for p53 expression by immunohistochemistry in association with other clinical parameters including WT1 mRNA expression in adult MDS patients.
Methods
We performed a retrospective study involving 29 BM biopsy samples from 24 patients with MDS between 2013 and 2014. The percentage of p53 staining positive cells was assessed based on a total manual count of 1000 BM hematopoietic cells. Clinical parameters were corrected from patient medical charts .
Results
The study included 17 males and 7 females. The median age at procedure was 71 years (range, 28-84). Five patients received sequential BM biopsies when clinical findings changed. According to WHO 2008 classification of MDS, 14 specimens were RCMD, 3 were RCMD-RS, 6 were RAEB-1 and 6 were RAEB-2. The result of cytogenetic analysis of 26 samples, showed complex karyotypes with more than 3 abnormalities found in 7 samples including 4 of complex karyotype with -5/5q-, isolated del5q was not found in this cohort and 11 were normal karyotype. Nine patients (11 specimens) were treated with azacitidine after first biopsy. With the median post-procedure follow up of 5.7 months (1-23.3 months), leukemic transformation and death occurred in one patient (two specimens) and two patients (three specimens), respectively. Positive rate of p53 expression in BM was as follows; <1%, 5 specimens; 1-3%, 8; 3-5%, 4; 5-10%, 4; >10%, 8. In 5 patients with sequential biopsies, p53 expression level of first sample was lower than it of second sample except in one patient who received azacitidine treatment after first biopsy. WT1 mRNA expression level in peripheral blood (PB) was as follows; <100 copies, 11; 101-1000copies, 8; >1000 copies, 6; 4 patients were not tested for WT1 mRNA level at the time of BM biopsy. Higher level of p53 expression was significantly associated with greater WT1 mRNA expression level in PB (r = 0.40, P = 0.05), complex cytogenetic abnormality (r = 0.64, P < 0.001), increasing with WHO2008 classification (r = 0.68, P < 0.001), IPSS (r = 0.50, P = 0.01), and IPSS-R (r = 0.53, P = 0.006). But it was not associated with percentage of CD34 positive cells in BM. In spite of short duration of follow-up time, high level of p53 expression was associated with overall survival (r = 0.54, P = 0.003).
Summary
High p53 protein expression in BM is associated with WT1 mRNA expression level and disease stage progression. It can be a predictor of survival in adult MDS.
Keyword(s): P53, WT1
Abstract: PB1827
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) is a heterogeneous disease. Several clinical findings were reported as prognostic markers. Identification of p53-positive cells by immunohistochemistry in bone marrow (BM) was demonstrated to correlate with presence of TP53 mutations, indicative of poor prognosis. Wilms’ tumor gene (WT1) mRNA expression was associated with the WHO classifications and risk evaluation of MDS. But there was no report about correlation between p53 expression and WT1 mRNA level.
Aims
We assessed BM biopsy specimens for p53 expression by immunohistochemistry in association with other clinical parameters including WT1 mRNA expression in adult MDS patients.
Methods
We performed a retrospective study involving 29 BM biopsy samples from 24 patients with MDS between 2013 and 2014. The percentage of p53 staining positive cells was assessed based on a total manual count of 1000 BM hematopoietic cells. Clinical parameters were corrected from patient medical charts .
Results
The study included 17 males and 7 females. The median age at procedure was 71 years (range, 28-84). Five patients received sequential BM biopsies when clinical findings changed. According to WHO 2008 classification of MDS, 14 specimens were RCMD, 3 were RCMD-RS, 6 were RAEB-1 and 6 were RAEB-2. The result of cytogenetic analysis of 26 samples, showed complex karyotypes with more than 3 abnormalities found in 7 samples including 4 of complex karyotype with -5/5q-, isolated del5q was not found in this cohort and 11 were normal karyotype. Nine patients (11 specimens) were treated with azacitidine after first biopsy. With the median post-procedure follow up of 5.7 months (1-23.3 months), leukemic transformation and death occurred in one patient (two specimens) and two patients (three specimens), respectively. Positive rate of p53 expression in BM was as follows; <1%, 5 specimens; 1-3%, 8; 3-5%, 4; 5-10%, 4; >10%, 8. In 5 patients with sequential biopsies, p53 expression level of first sample was lower than it of second sample except in one patient who received azacitidine treatment after first biopsy. WT1 mRNA expression level in peripheral blood (PB) was as follows; <100 copies, 11; 101-1000copies, 8; >1000 copies, 6; 4 patients were not tested for WT1 mRNA level at the time of BM biopsy. Higher level of p53 expression was significantly associated with greater WT1 mRNA expression level in PB (r = 0.40, P = 0.05), complex cytogenetic abnormality (r = 0.64, P < 0.001), increasing with WHO2008 classification (r = 0.68, P < 0.001), IPSS (r = 0.50, P = 0.01), and IPSS-R (r = 0.53, P = 0.006). But it was not associated with percentage of CD34 positive cells in BM. In spite of short duration of follow-up time, high level of p53 expression was associated with overall survival (r = 0.54, P = 0.003).
Summary
High p53 protein expression in BM is associated with WT1 mRNA expression level and disease stage progression. It can be a predictor of survival in adult MDS.
Keyword(s): P53, WT1
Type: Publication Only
Background
Myelodysplastic syndrome (MDS) is a heterogeneous disease. Several clinical findings were reported as prognostic markers. Identification of p53-positive cells by immunohistochemistry in bone marrow (BM) was demonstrated to correlate with presence of TP53 mutations, indicative of poor prognosis. Wilms’ tumor gene (WT1) mRNA expression was associated with the WHO classifications and risk evaluation of MDS. But there was no report about correlation between p53 expression and WT1 mRNA level.
Aims
We assessed BM biopsy specimens for p53 expression by immunohistochemistry in association with other clinical parameters including WT1 mRNA expression in adult MDS patients.
Methods
We performed a retrospective study involving 29 BM biopsy samples from 24 patients with MDS between 2013 and 2014. The percentage of p53 staining positive cells was assessed based on a total manual count of 1000 BM hematopoietic cells. Clinical parameters were corrected from patient medical charts .
Results
The study included 17 males and 7 females. The median age at procedure was 71 years (range, 28-84). Five patients received sequential BM biopsies when clinical findings changed. According to WHO 2008 classification of MDS, 14 specimens were RCMD, 3 were RCMD-RS, 6 were RAEB-1 and 6 were RAEB-2. The result of cytogenetic analysis of 26 samples, showed complex karyotypes with more than 3 abnormalities found in 7 samples including 4 of complex karyotype with -5/5q-, isolated del5q was not found in this cohort and 11 were normal karyotype. Nine patients (11 specimens) were treated with azacitidine after first biopsy. With the median post-procedure follow up of 5.7 months (1-23.3 months), leukemic transformation and death occurred in one patient (two specimens) and two patients (three specimens), respectively. Positive rate of p53 expression in BM was as follows; <1%, 5 specimens; 1-3%, 8; 3-5%, 4; 5-10%, 4; >10%, 8. In 5 patients with sequential biopsies, p53 expression level of first sample was lower than it of second sample except in one patient who received azacitidine treatment after first biopsy. WT1 mRNA expression level in peripheral blood (PB) was as follows; <100 copies, 11; 101-1000copies, 8; >1000 copies, 6; 4 patients were not tested for WT1 mRNA level at the time of BM biopsy. Higher level of p53 expression was significantly associated with greater WT1 mRNA expression level in PB (r = 0.40, P = 0.05), complex cytogenetic abnormality (r = 0.64, P < 0.001), increasing with WHO2008 classification (r = 0.68, P < 0.001), IPSS (r = 0.50, P = 0.01), and IPSS-R (r = 0.53, P = 0.006). But it was not associated with percentage of CD34 positive cells in BM. In spite of short duration of follow-up time, high level of p53 expression was associated with overall survival (r = 0.54, P = 0.003).
Summary
High p53 protein expression in BM is associated with WT1 mRNA expression level and disease stage progression. It can be a predictor of survival in adult MDS.
Keyword(s): P53, WT1
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