EVALUATION OF P53 PROTEIN EXPRESSION IN MYELODYSPLASTIC PATIENTS: PROGNOSTIC IMPACT IN A SINGLE CENTRE EXPERIENCE
(Abstract release date: 05/21/15)
EHA Library. Ricco A. 06/12/15; 103044; PB1821
Disclosure(s): University of Bari Medical SchoolDepartment of Emergency and Transplantation, Hematology Section
Alessandra Ricco
Contributions
Contributions
Abstract
Abstract: PB1821
Type: Publication Only
Background
AML follwing MDS has a very poor outcome, so accurate prediction is essential, expecially in patients who could potentially be cured by stem cell transplantation. A strong association between p53 protein expression, the TP53 mutation and an adverse outcome has been reported in various hematologic malignancies including MDS. Strong nuclear staining of the p53 protein by immunhistochemistry (IHC) has been used as a surrogate marker for TP53 gene mutation in hematologic and other malignancies; a strong correlation of p53 nuclear expression with TP53 mutation has also been demonstrated.
Aims
To assess the role of p53 expression in MDS patients as a new prognostic tool, as well as its feasibility in routine clinical practice, we analyzed the prevalence of p53 expression in a cohort of 62 consecutive bone marrow (BM) biopsies from patients with MDS at diagnosis, and correlated our findings to other validated prognostic markers and clinical outcome
Methods
The DO-7 antibody (DakoCytomation, Denmark), which labels both wild and mutant-type p53 proteins, was used to detect p53 expression (a colorectal carcinoma positive control was included on each slide). Diagnosis according to the 2008 WHO Classification was: isolated del (5q) in 4 cases, RA in12, RARS in 5, RCMD in 8, RAEB-1 in 15, RAEB-2 in 18.
Results
Among patients with strong p53 immunostaining in ≥ 1% of BM cells, we found significant correlations with BM blasts (70% RAEB-1/2, vs 32% in negative cases). IPSS-R cytogenetic risk was int/poor/very poor in 36% of positive and 0% in negative IHC cases. IPSS score was int-2/high in 54% of patients with strong positivity vs 20% in negative cases. BM fibrosis was present in 70% of positive vs. 30% of negative IHC cases. Transfusion dependency was observed in 50% of patients with p53 strong expression vs. 20% of negative cases. Moreover, we found that strong p53nuclear expression was associated with a significantly worse outcome (87% disease progression plus leukemic evolution vs. 20% in negative cases) and shorter median OS (18 months vs. 35 in negative cases).
Summary
Our data indicate that IHC p53 protein expression, evaluated in bone marrow biopsies by a widely available method, is a highly predictive marker and thus a helpful tool in risk assessment and the decision making process in MDS.
Session topic: Publication Only
Type: Publication Only
Background
AML follwing MDS has a very poor outcome, so accurate prediction is essential, expecially in patients who could potentially be cured by stem cell transplantation. A strong association between p53 protein expression, the TP53 mutation and an adverse outcome has been reported in various hematologic malignancies including MDS. Strong nuclear staining of the p53 protein by immunhistochemistry (IHC) has been used as a surrogate marker for TP53 gene mutation in hematologic and other malignancies; a strong correlation of p53 nuclear expression with TP53 mutation has also been demonstrated.
Aims
To assess the role of p53 expression in MDS patients as a new prognostic tool, as well as its feasibility in routine clinical practice, we analyzed the prevalence of p53 expression in a cohort of 62 consecutive bone marrow (BM) biopsies from patients with MDS at diagnosis, and correlated our findings to other validated prognostic markers and clinical outcome
Methods
The DO-7 antibody (DakoCytomation, Denmark), which labels both wild and mutant-type p53 proteins, was used to detect p53 expression (a colorectal carcinoma positive control was included on each slide). Diagnosis according to the 2008 WHO Classification was: isolated del (5q) in 4 cases, RA in12, RARS in 5, RCMD in 8, RAEB-1 in 15, RAEB-2 in 18.
Results
Among patients with strong p53 immunostaining in ≥ 1% of BM cells, we found significant correlations with BM blasts (70% RAEB-1/2, vs 32% in negative cases). IPSS-R cytogenetic risk was int/poor/very poor in 36% of positive and 0% in negative IHC cases. IPSS score was int-2/high in 54% of patients with strong positivity vs 20% in negative cases. BM fibrosis was present in 70% of positive vs. 30% of negative IHC cases. Transfusion dependency was observed in 50% of patients with p53 strong expression vs. 20% of negative cases. Moreover, we found that strong p53nuclear expression was associated with a significantly worse outcome (87% disease progression plus leukemic evolution vs. 20% in negative cases) and shorter median OS (18 months vs. 35 in negative cases).
Summary
Our data indicate that IHC p53 protein expression, evaluated in bone marrow biopsies by a widely available method, is a highly predictive marker and thus a helpful tool in risk assessment and the decision making process in MDS.
Session topic: Publication Only
Abstract: PB1821
Type: Publication Only
Background
AML follwing MDS has a very poor outcome, so accurate prediction is essential, expecially in patients who could potentially be cured by stem cell transplantation. A strong association between p53 protein expression, the TP53 mutation and an adverse outcome has been reported in various hematologic malignancies including MDS. Strong nuclear staining of the p53 protein by immunhistochemistry (IHC) has been used as a surrogate marker for TP53 gene mutation in hematologic and other malignancies; a strong correlation of p53 nuclear expression with TP53 mutation has also been demonstrated.
Aims
To assess the role of p53 expression in MDS patients as a new prognostic tool, as well as its feasibility in routine clinical practice, we analyzed the prevalence of p53 expression in a cohort of 62 consecutive bone marrow (BM) biopsies from patients with MDS at diagnosis, and correlated our findings to other validated prognostic markers and clinical outcome
Methods
The DO-7 antibody (DakoCytomation, Denmark), which labels both wild and mutant-type p53 proteins, was used to detect p53 expression (a colorectal carcinoma positive control was included on each slide). Diagnosis according to the 2008 WHO Classification was: isolated del (5q) in 4 cases, RA in12, RARS in 5, RCMD in 8, RAEB-1 in 15, RAEB-2 in 18.
Results
Among patients with strong p53 immunostaining in ≥ 1% of BM cells, we found significant correlations with BM blasts (70% RAEB-1/2, vs 32% in negative cases). IPSS-R cytogenetic risk was int/poor/very poor in 36% of positive and 0% in negative IHC cases. IPSS score was int-2/high in 54% of patients with strong positivity vs 20% in negative cases. BM fibrosis was present in 70% of positive vs. 30% of negative IHC cases. Transfusion dependency was observed in 50% of patients with p53 strong expression vs. 20% of negative cases. Moreover, we found that strong p53nuclear expression was associated with a significantly worse outcome (87% disease progression plus leukemic evolution vs. 20% in negative cases) and shorter median OS (18 months vs. 35 in negative cases).
Summary
Our data indicate that IHC p53 protein expression, evaluated in bone marrow biopsies by a widely available method, is a highly predictive marker and thus a helpful tool in risk assessment and the decision making process in MDS.
Session topic: Publication Only
Type: Publication Only
Background
AML follwing MDS has a very poor outcome, so accurate prediction is essential, expecially in patients who could potentially be cured by stem cell transplantation. A strong association between p53 protein expression, the TP53 mutation and an adverse outcome has been reported in various hematologic malignancies including MDS. Strong nuclear staining of the p53 protein by immunhistochemistry (IHC) has been used as a surrogate marker for TP53 gene mutation in hematologic and other malignancies; a strong correlation of p53 nuclear expression with TP53 mutation has also been demonstrated.
Aims
To assess the role of p53 expression in MDS patients as a new prognostic tool, as well as its feasibility in routine clinical practice, we analyzed the prevalence of p53 expression in a cohort of 62 consecutive bone marrow (BM) biopsies from patients with MDS at diagnosis, and correlated our findings to other validated prognostic markers and clinical outcome
Methods
The DO-7 antibody (DakoCytomation, Denmark), which labels both wild and mutant-type p53 proteins, was used to detect p53 expression (a colorectal carcinoma positive control was included on each slide). Diagnosis according to the 2008 WHO Classification was: isolated del (5q) in 4 cases, RA in12, RARS in 5, RCMD in 8, RAEB-1 in 15, RAEB-2 in 18.
Results
Among patients with strong p53 immunostaining in ≥ 1% of BM cells, we found significant correlations with BM blasts (70% RAEB-1/2, vs 32% in negative cases). IPSS-R cytogenetic risk was int/poor/very poor in 36% of positive and 0% in negative IHC cases. IPSS score was int-2/high in 54% of patients with strong positivity vs 20% in negative cases. BM fibrosis was present in 70% of positive vs. 30% of negative IHC cases. Transfusion dependency was observed in 50% of patients with p53 strong expression vs. 20% of negative cases. Moreover, we found that strong p53nuclear expression was associated with a significantly worse outcome (87% disease progression plus leukemic evolution vs. 20% in negative cases) and shorter median OS (18 months vs. 35 in negative cases).
Summary
Our data indicate that IHC p53 protein expression, evaluated in bone marrow biopsies by a widely available method, is a highly predictive marker and thus a helpful tool in risk assessment and the decision making process in MDS.
Session topic: Publication Only
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