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

[hodgkin lymphoma, classical]

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 , DOK 2 , SKAP 55 , ITK , and PKC α-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 , DOK 2 , SKAP 55 , 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 DOK 2 and SKAP 55 , and a proportion (47 %) of hairy cell leukemias were GADS . Notably , PKC α 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 T -lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS /DOK 2 /SKAP 55 /ITK ) and for the differential diagnosis between ALCL and PTCL /NOS (GADS /DOK 2 /SKAP 55 /ITK ) or classical Hodgkin lymphoma (PKC α ). Finally , association with specific tumor subtypes may have therapeutic potential .

Diseases
Validation

Diseases presenting "lymphoma" symptom

adrenal incidentaloma

alpha-thalassemia

carcinoma of the gallbladder

cushing syndrome

dedifferentiated liposarcoma

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

familial hypocalciuric hypercalcemia

focal myositis

hirschsprung disease

hodgkin lymphoma, classical

kabuki syndrome

liposarcoma

locked-in syndrome

monosomy 21

oculocutaneous albinism

primary effusion lymphoma

severe combined immunodeficiency

systemic capillary leak syndrome

waldenström macroglobulinemia

wiskott-aldrich syndrome

This symptom has already been validated