D T Finn | PubMed Health

PubMed1996

Correlation between clonotypic T-cell receptor beta chain variable region (TCR-V beta) gene expression and aberrant T-cell antigen expression in cutaneous T-cell lymphoma.

Immunohistochemical studies can augment the clinicopathologic diagnosis of cutaneous T-cell lymphoma (CTCL). Our goal was to determine whether a panel of 11 T-cell receptor (TCR) beta chain variable region (V beta) monoclonal antibodies (moAbs) could consistently identify clonal T-cell populations within CTCL skin infiltrates, and whether these cell exhibited aberrant T-cell antigen expression. Biopsies from 24 CTCL and 3 parapsoriasis patients were analyzed. Of the 27 patients, 4 (15%) demonstrated T-cell clonality by restricted TCR-V beta moAb staining. The V beta + restricted cells expressed aberrant antigen profiles. Overall, aberrant antigen profiles were detected in 18/24 (75%) CTCL. Patients. V beta 18 moAb crossreacted with a 85 kD protein produced by basal and suprabasal keratinocytes. We conclude: 1) Restricted TCR-V beta expression correlated with aberrant T-cell antigen profiles: 2) In the absence of a complete panel of TCR-V beta moAbs, localization of aberrant T-cell antigen expression can be useful in identifying malignant T-cells within CTCL skin infiltrates; 3) The detection sensitivity and specificity of the currently available TCR-V beta moAbs may limit their utility to consistently detect clonal T-cell populations in CTCL skin biopsies; 4) A 85 kD protein present on basal and suprabasal keratinocytes is recognized by V beta 18 moAb and may be related to immune function(s) of the epidermis.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1995

Large-cell transformation following detection of minimal residual disease in cutaneous T-cell lymphoma: molecular and in situ analysis of a single neoplastic T-cell clone expressing the identical T-cell receptor.

PURPOSE: One of the unique characteristics of cutaneous T-cell lymphoma (CTCL) is its ability to undergo cytologic transformation in which the malignant T cells develop the morphologic appearance of a large-cell lymphoma. Reported to occur in up to 20% of advanced cases, large-cell transformation (LCT) is associated with an aggressive clinical course. Little is known about the risk factors or the molecular mechanisms of LCT. Before current immunohistochemical and molecular techniques, it was not possible to determine if LCT represented changes of the initial neoplastic T-cell clone or, in fact, was a distinct second malignancy. The goal of this study was to define the clonal evolution of LCT in CTCL. PATIENTS AND METHODS: Polymerase chain reaction (PCR) amplification of T-cell receptor-beta (TCR-beta) gene rearrangements and immunohistochemistry with monoclonal antibodies to TCR-V beta regions were used as markers of T-cell clonality to analyze the skin and peripheral blood of a patient with CTCL and LCT. RESULTS: We first detected the presence of minimal residual disease (MRD) in a CTCL patient with a complete clinical response to biologic response modifiers (BRMs). When clinical relapse occurred and demonstrated LCT, TCR-beta-PCR and in situ immunohistochemistry with a specific TCR-V beta monoclonal antibody identified a single neoplastic T-cell clone that expressed the identical TCR as the original clone. CONCLUSION: Our results confirm a common clonal origin for CTCL and LCT. We also provide evidence of MRD in CTCL by molecular analysis, implying that residual malignant cells maintain a potential for clinical relapse and possibly LCT. The role of MRD detection remains to be defined in the clinical assessment of CTCL. LCT in CTCL provides a unique model to investigate the molecular events that underlie terminal-stage tumor progression.

Amino Acid Sequence↗