CD3

Summary

CD3 is a reliable marker of T cell lineage. Loss of expression is rare in T cell malignancies, and aberrant expression by other lineages is very infrequent.

Surface CD3 is acquired during thymic maturation, but is preceded by expression in cytoplams, smaking cytoplasmic CD3 is very useful in the diagnosis of acute T cell leukaemia.

On more mature neoplasms CD3 will be detected on the cell surface.

Normal expression and function

CD3 is not a single molecule, rather it is a multi-molecular complex (two epsilon (ε) chains, a gamma (γ) chain, a delta (δ) chain and a zeta (ζ) chain) that play a pivitol role in assembling and activating the T cell receptor. It is first expressed in the cytoplasm becoming expressed on as they mature. As an essential TCR component it is expressed almost exclusively by mature T cells.

Diagnostic role

• In T cell Acute Lymphocytic Leukaemia CD3 expression is mainly cytoplasmic (cyCD3). Surface (sCD3) is variably expressed in more mature forms of T-ALL.

• In mature T cell neoplasms sCD3 is found on T-prolymphocytic leukaemia, Sézary syndrome, Adult T cell leukaemia/lymphoma (ATLL), Angioimmunoblastic T cell lymphoma (AITL), T-Large granular lymphocytic leukaemia (T-LGL) and Hepatosplenic T-cell lymphoma.

• Natural Killer cell lymphoproliferative disorders do not express a conventional TCR so CD3 is not expressed.

• B cells will not express CD3, and aberrant expression in AML is rare (in contrast to other T cell marker such as CD2 or CD7).

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SUMMARY TABLES

Note Click here for KEY- diseases. The colour and % refer to the proportion of cases expressing the marker KEY - expression key. Additional comments on strength, or site of expression (if relevant) are given below the table.

Expression in primitive cell types
AML	CMML	B ALL	BL	T ALL	ETP ALL	MPAL	Hgn
<5%	<5%	<5%	<5%	80-100%	80-100%	20-40%	<5%

Notes: CD3 exprssion is considered a very strong indicator of T lineage or mixed phenotype in acute leukaemia; however the where CD3 expression is weak or found only by immunohistchemistry then care should be taken in interpretation (see notes on MPAL and ETP-ALL). Note also that CD3 expression in acute leukaemia may be cytoplasmic or surface depending on cell maturity

CD13 expression: mature B cell neoplasms
CLL	MCL	FL	MZL	HCL	DLBCL	LPL	PCL
<5%	<5%	<5%	<5%	<5%	<5%	<5%	<5%

Notes: CD3 expression is not seen in mature B lymphoid disorders

Expression in mature T cell neoplasms*
ATLL	CTCL / Sezary	T-PLL	T-LGL	NK-LGL
80-100%	80-100%	80-100%	80-100%	<5%

Notes: The level of CD3 expression is increased (compared to normal T cells) in T-PLL and T-LGL, and are lower than normal T cells in Sézary syndrome and ATLL.

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