Nuclear Expression of MATK Is a Novel Marker of Type II Enteropathic T-Cell Lymphoma and NK/T Cell Lymphoma
SY Tan, AS Ooi, J Ngeow, L Tan, BT Teh. Singapore General Hospital, Singapore, Singapore; National Cancer Centre, Singapore, Singapore
Background: Extranodal NK/T-cell lymphoma (NKTL) is relatively common in Asia but rare in western populations. Little is known about this neoplasm and novel biomarkers are needed to resolve diagnostic difficulties, improve prognostication and develop targeted therapies. We interrogated the transcriptome of NK and mature T-cell neoplasms by whole-genome expression profiling for novel biomarkers that are differentially expressed.
Design: Expression profiling was performed on 8 angioimmunoblastic T-cell lymphomas (AITL), 4 NKTL, 1 xenograft tumor and its cultured line that was derived from a NKTL, and 6 peripheral T-cell lymphomas (PTCL). Data were subjected to clustering analysis and validated by immunohistochemistry on 125 mature T cell lymphomas, including 58 NKTL, 28 PTCL, 3 subcutaneous panniculitis-like T-cell lymphomas, 9 type II enteropathy associated T-cell lymphoma (Type II EATL), 15 AITL and 12 alk+ anaplastic large cell lymphomas (ALCL).
Results: Three genes (KLRD1, Janus kinase, MATK) were differentially expressed in NKTL. Nuclear localization of MATK expression is more often seen in nasal NKTL compared to other neoplasms and ranged from >80% (4/28), 40-80%(12/28), 20-40% (8/28) to <20% (4/28). Extra-nasal NKTL comprises two subsets, one group showing high MATK nuclear expression of >80% (13/30) and the other (12/30) showing very low levels of nuclear staining for MATK (<20%). Of particular interest is the finding that high nuclear expression of MATK is seen in all 9 cases of Type II EATL. They display a typical CD8+ CD56+ EBER- TIA1+ phenotype, which distinguishes it from classical EATL and NKTL. For a relatively unknown disease that is only recently described, Type II EATL comprises the bulk of primary intestinal T-cell lymphomas (9/13) in our series.
Conclusions: MATK, KLRD1 and Janus kinase are differentially expressed in NKTL. MATK shows nuclear expression in CD8+ cytotoxic T-cells of intestinal mucosa (possible cell of origin) and emerged as a novel marker of Type II EATL. This disease is often misdiagnosed as a form of NKTL and constitutes a significant proportion of primary intestinal T-cell lymphoma in Asian patients, in whom celiac disease and classic EATL are rare. High level nuclear expression of MATK is also seen in a subset of extra-nasal NKTL, which has been associated with a poorer clinical outcome.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 193, Tuesday Morning