J Korean Med Sci.  2006 Aug;21(4):645-651. 10.3346/jkms.2006.21.4.645.

nm23-H1 Protein Expression and Gene Mutation in 150 Patients with Non-Hodgkin's Lymphomas

• Lee JH
• Cho SJ
• Zhang X
• Zheng Z
• Lee ES
• Kim A
• Kim YS
• Chae YS
• Kim I

• KMID: 2157815
• DOI: http://doi.org/10.3346/jkms.2006.21.4.645

Abstract

The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.

Keyword

nucleoside diphosphate kinase A; nm23-H1 Protein; Lymphoma, Non-Hodgkin; Mutation; Prog-nosis

MeSH Terms

Tissue Array Analysis
Survival Analysis
Prognosis
Polymorphism, Single-Stranded Conformational
Nucleoside-Diphosphate Kinase/*genetics/metabolism
Mutation/*genetics
Middle Aged
Male
Lymphoma, T-Cell/genetics/metabolism/pathology
Lymphoma, Non-Hodgkin/genetics/metabolism/*pathology
Lymphoma, Mantle-Cell/genetics/metabolism/pathology
Lymphoma, Large-Cell, Diffuse/genetics/metabolism/pathology
Lymphoma, B-Cell/genetics/metabolism/pathology
Immunohistochemistry
Humans
Female
DNA Mutational Analysis
Base Sequence

Figure

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  Fig. 1 The nm23-H1 protein expression by LSAB method. (A) (-), <5% positive cells; (B) (1+), 5-50% positive cells; (C) (2+), >50% positive cells.

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  Fig. 2 The survival curve according to nm23-H1 protein expression (p=0.0039). -, less than 5% of tumor cells were positive; 1+, 5-50% of tumor cells were positive; 2+, more than 50% of the tumor cells were positive.

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  Fig. 3 The survival curve of nm23-H1 protein expression in B cell lymphoma (A) and T cell lymphoma (B) (p=0.0013). -, less than 5% of tumor cells were positive; 1+, 5-50% of tumor cells were positive; 2+, more than 50% of the tumor cells were positive.

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  Fig. 4 The survival curve of nm23-H1 protein expression according to the same Ann Arbor clinical stage (A, Stage III and IV, p=0.0042) and the same International Prognostic Index (B, IPI 2 and 3, p=0.0483). -, less than 5% of tumor cells were positive; 1+, 5-50% of tumor cells were positive; 2+, more than 50% of the tumor cells were positive.

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  Fig. 5 nm23-H1 mutation by sequencing. (A) All of four cases with exon 1 mutation show the point mutation at the same site (*, C ← G). (B) Three of four cases with exon 2 mutation reveal the insertional mutation at the same site (*).

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