Intracellular TCR-signaling pathway: Novel markers for lymphoma diagnosis and potential therapeutic targets

Claudio Agostinelli, Hasan Rizvi, Jennifer Paterson, Vishvesh Shende, Ayse U. Akarca, Elena Agostini, Fabio Fuligni, Simona Righi, Sebastiano Spagnolo, Pier Paolo Piccaluga, Edward A. Clark, Stefano A. Pileri, Teresa Marafioti

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα- involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS+. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of Tlineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

Original languageEnglish
Pages (from-to)1349-1359
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume38
Issue number10
Publication statusPublished - 2014

Keywords

  • Immunohistochemistry
  • Lymphomas
  • T-cell receptor signaling
  • Tissue microarray

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery
  • Medicine(all)

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