Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type

Giuseppe Lo Bello,Stefano A Pileri,Stefan Dojcinov,Ayse U Akarca,Yasodha Natkunam,Maria Raffaella Ambrosio,Lorenzo Leoncini,Matt Pugh,Elena Sabattini,Claudio Agostinelli,Monique Delisser,Shuchun Zhao,Teresa Marafioti,Alan Ramsay,Hernan Molina-Kirsch,Manuel Rodriguez-Justo

doi:10.1007/s00428-018-2434-x

Abstract

Granulysin is a cytolytic protein expressed in cytotoxic T and natural killer (NK) cells. Abnormal serum levels of granulysin in lymphomas with NK and cytotoxic phenotype have been shown to correlate with tumour progression. In this study, we investigated the expression pattern of granulysin in routine sections of normal and reactive lymphoid tissues as well as in a large series of lymphomas. In normal tissues, granulysin labelled a small population of cells that double immunostaining revealed to belong to the pool of cytotoxic T/NK cells. Among lymphoid neoplasms, the highest expression of granulysin (71%) was found in extranodal NK/T cell lymphomas of nasal type (ENKTL). To note is that 29% of ENKTLs, which were negative for one or more of classical cytotoxic markers strongly expressed granulysin. Furthermore, expression of granulysin was observed in rare cases of T cell lymphomas with a cytotoxic phenotype (i.e. ALK-negative anaplastic large cell lymphoma (26%), enteropathy-associated T cell lymphoma (12%) and peripheral T cell lymphoma, NOS (4%)). None of the investigated non-Hodgkin B cell lymphomas, Hodgkin lymphoma and plasma cell myeloma were granulysin positive. The results suggest granulysin as a novel marker for a subset of cytotoxic NK cell derived malignancies and its usefulness is highlighted in those ENKTLs that lack expression of other cytotoxic markers but retain granulysin expression.

Highlights

Granulysin is a sposin-like lipid-binding protein that was originally described in 1998 as a human antimicrobial peptide with a broad activity against intracellular pathogens [1]
We show that granulysin is expressed in cytotoxic/natural killer (NK) lymphocytes and in subsets of NK/T cell derived lymphomas
Our findings showed that the majority of granulysinpositive cells co-expressed CD56 while most of the CD4+ and CD8+ T cells were negative for granulysin

Summary

Introduction

Granulysin is a sposin-like lipid-binding protein that was originally described in 1998 as a human antimicrobial peptide with a broad activity against intracellular pathogens [1]. The protein was initially identified as a cytolytic and proinflammatory molecule expressed by natural killer (NK) cells and activated cytotoxic T lymphocytes (CTLs) [2, 3] Several studies have shown the clinical relevance of granulysin in a number of physiologic conditions including reproductive biology, innate immunity, dendritic cell chemotaxis and activation as well as in infectious diseases and in cancers [5,6,7]. The findings led to suggest granulysin as a potential diagnostic and prognostic marker for these lymphoma types [8]

Methods

Results

Conclusion