C-MYC overexpression predicts aggressive transformation and a poor outcome in mucosa-associated lymphoid tissue lymphomas

Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common, indolent B-cell lymphoma. MALT lymphoma with large tumor cells (LTCs) is believed to have the potential to transform to aggressive diffuse large B-cell lymphoma (DLBCL) which may have a poor prognosis. C-MYC is a transcription factor. Its translocation and overexpression predicts an inferior prognosis and poor response to therapy in cases of DLBCL. In the current study, C-MYC expression was detected in MALT lymphomas, and its relationship to the occurrence of LTCs, clinicopathological parameters and prognosis was assessed. A total of 69 cases were enrolled in the study, including 42 cases of MALT lymphoma without LTCs, 20 cases of MALT lymphoma with LTCs and 7 cases of DLBCL with a MALT lymphoma component (DLBCL+MALT). Immunohistochemistry and fluorescent in situ hybridization analyses were performed. In total, 15/42 (35.7%) cases were nuclear positive for C-MYC expression in the group without LTCs, whereas 15/20 (75.0%) and 4/7 (57.1%) cases were positive in the group with LTCs and in the group with DLBCL+MALT, respectively (P=0.004). Univariate and multivariate analysis were used to determine the correlations of C-MYC expression and clinicopathological parameters with overall survival (OS). C-MYC expression, Ann Arbor stage, LDH level and IPI were considerably associated with OS according to the univariate analysis. However, only C-MYC expression ≥ 20% showed a statistical significance in the multivariate analysis (HR=20.604, 95% CI: 1.909-222.412, P=0.013). Therefore, C-MYC overexpression may play an important role in aggressive transformation and is an independent prognostic factor in MALT lymphoma.

Keywords: C-MYC; MALT lymphoma; fluorescent in situ hybridization; immunohistochemistry; prognosis.

Figure 1

A. MALT lymphoma without large tumor cells (×400). B. MALT lymphoma with large tumor cells showing centroblast- or immunoblast-like large cells scattered among the small tumor cells (×400).

Figure 2

A. Staining shows that both large and small tumor cells were positive for C-MYC in MALT lymphoma (×400). B. In one of the DLBCL+MALT cases, 80% of tumor cells show strong nuclear staining for C-MYC (×200).

Figure 3

It shows the C-MYC expression of each case in all 62 MALT lymphomas.

Figure 4

C-MYC translocation in a DLBCL+MALT case as shown by split fluorescent in situ hybridization (FISH) signals.

Figure 5

Kaplan-Meier survival curves with respect to C-MYC expression (A and B), LDH level (C), IPI (D), cellular composition (E) and Ann Arbor stage (F).