p53 protein expression in patients with myelodysplasia treated with allogeneic bone marrow transplantation

Pich,Achille; Godio,Laura; Davico Bonino,Laura

doi:10.3892/mco.2017.1225

p53 protein expression in patients with myelodysplasia treated with allogeneic bone marrow transplantation

Authors:
- Achille Pich
- Laura Godio
- Laura Davico Bonino
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Affiliations: Department of Molecular Biotechnology and Health Sciences, Section of Pathology, University of Turin, I‑10126 Turin, Italy, Azienda Ospedaliera Città della Salute e della Scienza, Anatomia e Istologia Patologica 1U, I‑10126 Turin, Italy
Published online on: April 21, 2017 https://doi.org/10.3892/mco.2017.1225
Pages: 876-880

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Abstract

Tumor protein 53 mutations adversely affect the prognosis of myelodysplastic syndromes (MDS); however, few studies have reported on the prognostic significance of the expression of p53 protein in MDS. The current study investigated p53 immunoreactivity (p53-IR) in bone marrow biopsies (BMBs) obtained at diagnosis from 18 patients (6 females and 12 males; mean age, 50.5 years) with MDS that underwent bone marrow transplantation (BMT) to determine the associations between clinical and histopathological data and outcome. There were 5 refractory cytopenia with multilineage dysplasia (RCMD) and 13 refractory anemia with excess blasts, type 2 (RAEB‑2) cases. p53‑IR was assessed as the percentage of hematopoietic cells exhibiting intense nuclear staining. The cut off for positivity was 5% of stained cells. A positive p53‑IR was detected in 7 patients (38.9%) and was associated with age (P=0.005) and pattern of BM fibrosis (P=0.03). A positive p53‑IR was more frequent in females, in highly cellular BMBs and in RAEB‑2 cases. Overall survival (OS) was associated with patients' age (P=0.01), hemoglobin level (P=0.04), type of MDS (P=0.05), degree of BM fibrosis (P=0.006) and number of BM blasts (P=0.05). The OS of patients with negative p53‑IR tended to be longer compared with that of patients with positive p53‑IR, although this difference was not statistically significant (P=0.1). Despite the limitation of the low number of cases, the present results indicate that a positive p53‑IR at diagnosis is associated with clinically more aggressive MDS subtypes and adverse histological prognostic factors, such as BM fibrosis. Therefore, the evaluation of p53 expression of BMBs of patients with MDS may be introduced in the histopathological work‑up of the disease.

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1	Brunning RD, Orazi A, Germing U, Le Beau MM, Porwit A, Bauman I, Vardiman JW and Hellstrom-Lindberg E: Myelodysplastic syndromes/neoplasms, overviewWHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, Thiele J and Vardiman JW: 4th. IARC Press; Lyon: pp. 88–93. 2008
2	Nagoshi H, Horiike S, Kuroda J and Taniwaki M: Cytogenetic and molecular abnormalities in myelodysplastic syndrome. Curr Mol Med. 11:678–685. 2011. View Article : Google Scholar : PubMed/NCBI
3	Kaneko H, Misawa S, Horiike S, Nakai H and Kashima K: TP53 mutations emerge at early phase of myelodysplastic syndrome and are associated with complex chromosomal abnormalities. Blood. 85:2189–2193. 1995.PubMed/NCBI
4	Christiansen DH, Andersen MK and Pedersen-Bjergaard J: Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype and a poor prognosis. J Clin Oncol. 19:1405–1413. 2001. View Article : Google Scholar : PubMed/NCBI
5	Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D and Ebert BL: Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 364:2496–2506. 2011. View Article : Google Scholar : PubMed/NCBI
6	Kerns BM, Jordan PA, Moore MB, Humphrey PA, Berchuck A, Kohler MF, Iglebart RC Jr, Bast JD and Marks JR: p53 overexpression in formalin-fixed, paraffin-embedded tissue detected by immunohistochemistry. J Histochem Cytochem. 40:1047–1051. 1992. View Article : Google Scholar : PubMed/NCBI
7	Iggo R, Gatter K, Bartek J, Lane D and Harris AL: Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 335:675–679. 1990. View Article : Google Scholar : PubMed/NCBI
8	Chang H, Yeung J, Qi C and Xu W: Aberrant nuclear p53 protein expression detected by immunohistochemistry is associated with hemizygous P53 deletion and poor survival for multiple myeloma. Br J Haematol. 138:324–329. 2007. View Article : Google Scholar : PubMed/NCBI
9	Chen MH, Qi CX, Saha MN and Chang H: p53 nuclear expression correlates with hemizygous TP53 deletion and predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with lenalidomide. Am J Clin Pathol. 137:208–212. 2012. View Article : Google Scholar : PubMed/NCBI
10	Chang H, Jiang AM and Qi CX: Aberrant nuclear p53 expression predicts hemizygous 17p (TP53) deletion in chronic lymphocytic leukemia. Am J Clin Pathol. 133:70–74. 2010. View Article : Google Scholar : PubMed/NCBI
11	Jädersten M, Saft L, Smith A, Kulasekararaj A, Pomplun S, Göhring G, Hedlund A, Hast R, Schlegelberger B, Porwit A, et al: TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 29:1971–1979. 2011. View Article : Google Scholar : PubMed/NCBI
12	Kulasekararaj AG, Smith AE, Mian SA, Mohamedali AM, Krishnamurthy P, Lea NC, Gäken J, Pennaneach C, Ireland R, Czepulkowski B, et al: TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol. 160:660–672. 2013. View Article : Google Scholar : PubMed/NCBI
13	Müller-Thomas C, Rudelius M, Rondak IC, Haferlach T, Schanz J, Huberle C, Schmidt B, Blaser R, Kremer M, Peschel C, et al: Response to azacitidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia. Haematologica. 99:e179–e181. 2014. View Article : Google Scholar : PubMed/NCBI
14	Orazi A, Cattoretti G, Heerema NA, Sozzi G, John K and Neiman RS: Frequent p53 overexpression in therapy related myelodysplastic syndromes and acute myeloid leukemias: An immunohistochemical study of bone marrow biopsies. Mod Pathol. 6:521–525. 1993.PubMed/NCBI
15	Kitagawa M, Yoshida S, Kuwata T, Tanizawa T and Kamiyama R: p53 expression in myeloid cells of myelodysplastic syndromes. Association with evolution of overt leukemia. Am J Pathol. 145:338–444. 1994.PubMed/NCBI
16	Brynes RK, Wilson CS, Kim AB and McCourty A: Expression of p53, MDM2, p21waf1, bcl-2, and retinoblastoma gene proteins in myelodysplastic syndrome after autologous bone marrow transplantation for lymphoma. Mod Pathol. 10:1120–1127. 1997.PubMed/NCBI
17	Saft L, Karimi M, Ghaderi M, Matolcsy A, Mufti GJ, Kulasekararaj A, Göhring G, Giagounidis A, Selleslag D, Muus P, et al: p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q). Haematologica. 99:1041–1049. 2014. View Article : Google Scholar : PubMed/NCBI
18	Porta MG Della, Malcovati L, Boveri E, Travaglino E, Pietra D, Pascutto C, Passamonti F, Invernizzi R, Castello A, Magrini U, et al: Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol. 27:754–762. 2009. View Article : Google Scholar : PubMed/NCBI
19	Cazzola M and Malcovati L: Prognostic classification and risk assessment in myelodysplastic syndromes. Hematol Oncol Clin North Am. 24:459–468. 2010. View Article : Google Scholar : PubMed/NCBI
20	Sugimoto K, Hirano N, Toyoshima H, Chiba S, Mano H, Takaku F, Yazaki Y and Hirai H: Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Blood. 81:3022–3026. 1993.PubMed/NCBI