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

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.

Extranodal NK/T-Cell Lymphomas: The Role of Natural Killer Cells and EBV in Lymphomagenesis

“…Certain markers, such as granulysin, a saposin-like protein that functions as a pro-inflammatory and cytolytic molecule expressed by cytotoxic T-cells and NK cells, are expressed in NK cells and NK-cell-derived neoplasms. Granulysin-expressing cells often co-expressed CD56, whereas most CD4-and CD8-positive T-cells did not express granulysin in a study by Bello et al [9] and can at times be the only positive marker when other cytotoxic markers are negative.…”

Extranodal NK-/T-cell lymphoma, nasal type: what advances have been made in the last decade?

“…Cytotoxic granules like perforin, TIA-1, and granzyme-B are usually positive. Granulysin also seems to be a useful marker for ENKTCL, especially when lacking expression of other common markers ( 30 , 31 ).…”

Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer

“…However, little evidence of the role of granulysin in antitumor immunity are available, since in vivo activity has not been completely demonstrated. Increased granulysin expression has been correlated to good prognosis in a wide variety of cancers, including solid and hematological malignancies [165][166][167][168][169][170]. Therapeutic strategies based on granulysin analogues have been studied, showing in vitro activity in cell lines and primary chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) cells [171].…”