The Correlation Between TP53 Expression and Ki-67 Proliferation with Bartl Malignancy Degree of Plasma Cell Neoplasm

Isabelle Deli Lestadi, Nurjati Chaerani Siregar, Puspita Eka Wuyung


BACKGROUND: Plasma cell neoplasm (PCN) is a neoplastic plasma cell proliferation which includes solitary bone plasmacytoma (SBP), extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Bartl classifies the degrees of PCN as low, intermediate and high. The aim of this study is to find the correlation between tumor suppressor gene p53 (TP53) expression and Ki-67 proliferation with Bartl malignancy degree of PCN. Therefore earlier PCN diagnostic method to prevent the development of PCN into MM can be found.

METHODS: Thirty-two PCN cases were classified into three groups based on Bartl’s degrees of malignancy. TP53 and Ki-67 immunohistochemical staining were performed on samples and the percentage of positivity was evaluated.

RESULTS: The Bartl’s low degree of malignancy was found in 10 MM cases (31.2%), intermediate degree in  5 SBP cases (15.6%) and high in 2 SBP and EMP cases (6.2%). TP53 expression was obtainable at 4% of low, 16% of intermediate and 10% of high degree. There was a significant difference between TP53 expression in low and intermediate degree (p=0.004). Mean proliferation index of Ki-67 was 57% in low, 44.6% in intermediate, and 32.6% in high degree. There was no significant difference of Ki-67 proliferation indexes among the group (p=0.339).

CONCLUSION: Increasing expression TP53 was in accord with Bartl’s degrees of malignancy, especially in low and intermediate degree, but there was no significant difference between Ki-67 proliferation index and Bartl’s degrees of malignancy.

KEYWORDS: plasmacytoma, myeloma, TP53, Ki-67, Bartl classification

Full Text:



Knobel D, Zouhair A, Tsang RW, Poortmans P, Belkacémi Y, Bolla M, et al. Prognostic factors in solitary plasmacytoma of the bone: a multicenter Rare Cancer Network study. BMC Cancer. 2006; 6: 118, CrossRef.

Badan Registrasi Kanker Perhimpunan Dokter Spesialis Patologi Indonesia. Kanker di Indonesia tahun 2010: Data histopatologik. Jakarta: Yayasan Kanker Indonesia; 2010.

Lorsbach R, Kluin PM. Plasma cell myeloma. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2013. p.312-5, NLMID.

National Cancer Institute [Internet]. Bethesda: National Institutes of Health; 2015. Plasma cell neoplasms (including multiple myeloma) treatment (PDQ®) - patient version [Updated Mar 16, 2015; cited Jul 9, 2015]. Available from:

Schols SEM, Tick LL. Recurrent extramedullary plasmacytoma in asymptomatic multiple myeloma: a case report. J Med Case Rep. 2015; 9: 37, CrossRef.

Neri A, Baldini L, Trecca D, Cro L, Polli E, Maiolo AT. p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy. Blood. 1993; 81: 128-35, PMID.

Bartl R, Frisch B. Diagnostic morphology in multiple myeloma. Current Diagn Pathol. 1995; 2: 222-35, CrossRef.

Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary plasmacytoma of bone and extramedullary plasmacytoma. Scientific World Journal. 2012; 2012: 895765, CrossRef.

Dores GM, Landgren O, McGlynn KA, Curtis RE, Linet MS, Devesa SS. Plasmacytoma of bone, extramedullary plasmacytoma and multiple myeloma: incidence and survival in the United States, 1992-2004. Br J Hematol. 2009; 144: 86-94, CrossRef.

Balakumaran A, Robey PG, Fedarko N, Landgren O. Bone marrow microenvironment in myelomagenesis: its potential role in early diagnosis. Expert Rev Mol Diagn. 2010; 10: 465-80, CrossRef.

Cook JR. Molecular pathology of plasma cell neoplasm. In: Dunphy CH, editor. Molecular Pathology of Hematolymphoid Diseases. New York: Springer; 2010. p.241-7, CrossRef.

Sheth N, Yeung J, Chang H. p53 nuclear accumulation is associated with extramedullary progression of multiple myeloma. Leuk Res. 2009; 33: 1357-60, CrossRef.

Alexandrakis MG, Passam FH, Dambaki C, Pappa CA, Stathopoulos EN. The relation between bone marrow angiogenesis and the proliferation index Ki-67 in multiple myeloma. J Clin Pathol. 2004; 57: 856-60, CrossRef.

Alexandrakis MG, Passam FH, Kyriakou DS, Dambaki K, Niniraki M, Stathopoulos EN. Ki-67 proliferation index: correlation with prognostic parameters and outcome in multiple myeloma. Am J Clin Oncol. 2004; 27: 8-13, CrossRef.

Lorsbach RB, Hsi ED, Dogan A, Fend F. Plasma cell myeloma and related neoplasms. Am J Clin Pathol. 2011; 136: 168-82, CrossRef.

Nussrat FL, Ali HH, Hussein HG, Al-Ukashi RJ. Immunohistochemical expression of ki-67 and p53 in colorectal adenomas: a clinicopathological study. Oman Med J. 2011; 26: 229-34, CrossRef.

Kremer M, Ott G, Nathrath M, Specht K, Strecker K, Alexiou C, et al. Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differences revealed by immunohistochemical analysis. J Pathol. 2005; 205: 92-101, CrossRef.

Shuaib A. Multiple myeloma. Haematology Updates. 2010; [n.v]: 53-8.

Kumar L, Verma R, Radhakrishnan VR. Recent advances in the management of multiple myeloma. Natl Med J India. 2010; 23: 210-8, PMID.

Al-Farsi K. Multiple myeloma: an update. Oman Med J. 2013; 28: 3-11, CrossRef.

Pratt G. Molecular aspects of multiple myeloma. Mol Pathol. 2002; 55: 273-83, CrossRef.

Dimopoulos MA, Moulopoulos LA, Maniatis A, Alexanian R. Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood. 2000; 96: 2037-44, PMID.

International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003; 121: 749-57, CrossRef.

Zuo Z, Tang Y, Bi CF, Zhang WY, Zhao S, Wang XQ, et al. Extraosseous (extramedullary) plasmacytomas: a clinicopathologic and immunophenotypic study of 32 Chinese cases. Diagn Pathol. 2011; 6: 123, CrossRef.

Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF. Tumors of the lymph nodes and spleen. Washington: Armed Forces Institute of Pathology; 1995, NLMID.

Bartl R, Frisch B, Burkhardt R, Fateh-Moghadam A, Mahl G, Gierster P, et al. Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging. Br J Haematol. 1982; 51: 361-75, CrossRef.

Jayashankar E, Roshinipaul T. Prognostication of histomorphological characteristics in multiple myeloma. J Cancer Sci Ther. 2010; 2: 153-6, CrossRef.

Milla F, Oriol A, Aguilar JL, Aventin A, Ayats R, Alonso E, et al. Usefulness and reproducibility of cytomorphologic evaluations to differentiate myeloma from monoclonal gammopathies of unknown significance. Am J Clin Pathol. 2001; 115: 127-35, CrossRef.

Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet oncol. 2014; 15: e538-48, CrossRef.

Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009; 23: 3-9, CrossRef.

Gastinne T, Leleu X, Duhamel A, Moreau AS, Franck G, Andrieux J, et al. Plasma cell growth fraction using Ki67 antigen expression identifies a subgroup of multiple myeloma patients displaying short survival within the ISS stage I. Eur J Hematol. 2007; 79: 297-304, CrossRef.

Girino M, Riccardi A, Luoni R,Ucci G, Cuomo A. Monoclonal antibody Ki-67 as a marker of proliferative activity in monoclonal gammopathies. Acta Haematol. 1991; 85: 26-30, CrossRef.

Pruneri G, Carboni N, Baldini L, Intini D, Colombi M, Bertolini F, et al. Cell cycle regulators in multiple myeloma: prognostic implications of p53 nuclear accumulation. Human Pathol. 2003; 34: 41-7, CrossRef.

Schwartz TH, Rhiew R, Isaacson SR, Orazi A, Bruce JN. Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study. Neurosurgery. 2001; 49: 1039-45, CrossRef.


Copyright (c) 2017 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute