Prognostic Impact of Immunohistochemical P53 Expression in Bone Marrow Biopsy in Higher Risk Mds: A Pilot Study

Abstract

Background and objectives:
 Mutations of the TP53 gene have an unfavorable prognosis in Myelodysplastic Syndromes (MDS). The product of the TP53gene is the p53 protein. Most of TP53mutations entail the accumulation of the protein in the nucleus of tumor cells. The immunohistochemical (IHC) staining for p53 can be a surrogate suggesting a mutational status and, if overexpressed, seems to be of prognostic value by itself. The best prognostic cut-off value of overexpression is controversial. The aim of this pilot study is to investigate about the correct value from a homogenous group of patients with higher IPSS-R risk MDS.
 Methods:
 In sixty consecutive patients diagnosed with MDS and categorized as IPSS-R risk “intermediate”, “high” and “very high”, the bone marrow biopsies performed at the diagnosis were retrospectively re-examined for IHC p53 expression. The result of p53 expression was subsequently related to survival. 
 Results:
 A worst overall survival was observed both in patients whose IHC p53 expression was ≥5% and ≥ 10% compared to the patients with a p53 expression respectively below 5% (p= 0.0063) or 10% (p=0.0038). 
 Conclusions:
 The ICH p53 expression in bone marrow biopsy in higher risk MDS was confirmed to have prognostic value. These results indicate more than 10% expression as the best cut off value.

High‐level MYC expression associates with poor survival in patients with acute myeloid leukemia and collaborates with overexpressed p53 in leukemic transformation in patients with myelodysplastic syndrome

“…MYC expression did not show any prognostic impact on OS in MDS patients (Figure 1F). In contrast, MDS patients with p53 expression showed significantly poor OS compared to MDS patients without p53 expression ( P < .0001; Figure 1G), compatible with findings in the literature 12,14,16 …”

“…Expression of p53 is significantly increased in both AML and MDS patients compared with the control group in our study. Similar to previous reports, 10,12,14,15,17,18 our study also found that p53 expression is a poor prognostic factor and confers a negative impact on OS in AML and MDS patients. P53 expression is correlated with TP53 aberration in 23 AML patients (85%, n = 27) and seven MDS patients (78%, n = 9), respectively.…”

“…In each case, at least five representative areas and more than 200 cells in each area were assessed and any positive cells determined by software algorithm were included. We used a cutoff of ≥5% 3+ nuclear staining of p53 for reporting positive protein expression 14‐16 . The cutoff of MYC expression was ≥8% 3+ nuclear staining, which was determined using an upper limit value of 99.7% interval value of our control group based on normal distribution model.…”

“…In previous studies, p53 expression was used as a surrogate marker of TP53 mutation in MDS and AML 10,12,13 . Expression of p53, defined as 3+ nuclear staining that involved ≥5% of bone marrow cellularity in both MDS and de novo AML patients, was considered a clinically meaningful cutoff 14‐16 . Similar to TP53 mutation, p53 expression was significantly associated with MDS patients with high‐risk cytogenetic abnormalities and with AML patients with myelodysplastic‐related changes carrying complex karyotypes and TP53 mutations 10,13 .…”

“…Similar to TP53 mutation, p53 expression was significantly associated with MDS patients with high‐risk cytogenetic abnormalities and with AML patients with myelodysplastic‐related changes carrying complex karyotypes and TP53 mutations 10,13 . P53 expression conferred a negative impact on overall survival (OS) in patients with therapy‐related myeloid neoplasms or MDS and relapse‐free survival (RFS) in patients with de novo AML 10,12,14,15,17,18 …”