Mantle Cell Lymphoma in Taiwan: Clinicopathologic and Molecular Characteristics and Tumor Immune Microenvironment

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma (B-NHL) with a largely aggressive clinical course. Due to the rarity of this tumor, it is quite difficult to collect a large series of MCL cases in Taiwan. To date, the largest series of MCL with detailed immunophenotyping in Taiwan included only 21 patients.MCL is usually composed of monomorphic small to medium-sized lymphoid cells with irregular nuclei, and a CCND1 translocation resulting in cyclin D1 overexpression can be detected in >95% of cases. A minor subgroup of MCL cases are composed of large lymphoid cells with blastoid or pleomorphic nuclei (blastoid and pleomorphic variants), and these tumors have an even more aggressive biological behavior. In addition, rare cyclin D1(-) MCL cases could lack the CCND1 translocation and cyclin D1 overexpression, but they still have clinical and gene expression features similar to those of cyclin D1(+) MCL cases..During the past decade, immunotherapies modulating the immune response against tumors have achieved remarkable success in various types of cancers. At the same time, the tumor immune microenvironment (TIME) has been increasingly recognized to play an important role in tumor biology, including patient prognosis and treatment response. Compared to other more common B-NHLs, the TIME of MCL is largely unknown.In recent years, we found that cyclin D1 negativity is surprisingly common in pleomorphic MCL (Chuang WY et al. Histopathology 2017; 70: 986-999). Furthermore, we found that cases previously diagnosed as SOX11-positive diffuse large B-cell lymphoma (DLBCL) are actually CD5/cyclin D1 double-negative pleomorphic MCL, and genetic and gene expression studies can be used to confirm the diagnosis (Chuang WY et al. Am J Surg Pathol 2019 Epub ahead of print). Our findings are helpful to prevent cases of pleomorphic MCL with aberrant immunophenotypes from being misdiagnosed as DLBCL. Based on our experience in pleomorphic MCL studies, we would like to clarify the clinicopathologic and molecular features and TIME of MCL in Taiwan.In our pilot study of 93 MCL patients in Taiwan, we established an immunohistochemical method for risk stratification. Using three markers of tumor cells (Ki-67, MYC and p53) and one marker of immune cells (IDO), we can stratify MCL patients into three risk groups, with a P-value of 0.000028. We would like to pursue our study on a larger cohort of patients about more immunophenotypic and genetic parameters.In this study, we will collect 200 cases of MCL from Chang Gung Memorial Hospital and Chi-Mei Medical Center, including consultation cases. Detailed clinicopathologic, immunophenotypic, genomic, gene expression and TIME workups will be performed. Our study will clarify the clinicopathologic and molecular nature of MCL in Taiwan. Our results will potentially improve the risk stratification and find therapeutic targets for MCL patients in Taiwan.

Project IDs

Project ID:PC10907-1125
External Project ID:MOST109-2314-B182-063
StatusFinished
Effective start/end date01/08/2031/07/21

Keywords

  • Mantle cell lymphoma
  • Taiwan
  • subclassification
  • pleomorphic
  • CD5
  • cyclin D1
  • SOX11
  • clinical features
  • prognosis
  • pathology
  • genomics
  • gene expression
  • tumor immune microenvironment

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