Abstract

Mantle cell lymphoma (MCL) is a relatively rare subtype of non-Hodgkin’s lymphoma. To identify molecular biomarkers in MCL, we performed immunohistochemistry tissue arrays using biopsies from 64 MCL patients diagnosed in West China Hospital from 2012 to 2016. TP53 mutation status in those patients was also examined by sequencing. The sequencing results showed TP53 mutations were highly heterogeneous in MCL. We identified four novel TP53 mutations in MCL: P151R, G199R, V218E, and G325R. The MCL patients with TP53 mutations had inferior progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.011). Tissue array results showed the expression of p53, Sox11, or Pax5 alone did not correlate with the patient PFS and OS. However, the MCL patients with triple-positive expression of p53/Sox11/Pax5 had inferior PFS (p = 0.008) and OS (p = 0.002). Such risk stratification was independent to the mantle cell lymphoma international prognostic index (MIPI), Ki-67 value, and TP53 mutation status of the patients. The triple-positive patients might represent a subtype of high-risk MCL. Our findings might indicate a novel way to stratify MCL and predict patients’ prognosis.

Highlights

  • Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin’s lymphoma (NHL) and accounts for about 6% of all NHL c­ ases1

  • Our findings suggested that Sox11 and Pax5 alone do not correlate with MCL Progression-free survival (PFS) and overall survival (OS)

  • According to the literatures and databases, four TP53 mutations detected in our patients—P151R, G199R, V218E, and G325R—had never been reported in MCL

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Summary

Introduction

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin’s lymphoma (NHL) and accounts for about 6% of all NHL c­ ases. Based on an epidemiology study in the United States, the incidence rate of MCL was about 0.5 to 0.6 per 100,000 persons, and the rate has increased 2–3 times in the past d­ ecades. The primary genetic event of MCL is translocation t(11;14)(q13;q32), which results in cyclin D1 overexpression. There are many heterogeneous secondary genetic alterations in MCL. Mutations in INK4A4, ATM5, CDK46, and TP537 genes are commonly seen in different MCL patients. Those alterations further target the cell signaling pathways, such as cell cycle progression, DNA damage response, and cell survival regulation, promoting tumor ­malignancy. Our data suggested a novel risk stratification of MCL based on immunohistochemistry (IHC) analysis of target antigens’ expression

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