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Diagnostic and prognostic importance of T‐cell receptor gene analysis in patients with Sézary syndrome
Author(s) -
FraserAndrews Elisabeth A.,
RussellJones Robin,
Woolford Alison J.,
Wolstencroft Robin A.,
Dean Alan J.,
Whittaker Sean J.
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20011001)92:7<1745::aid-cncr1689>3.0.co;2-0
Subject(s) - cd8 , t cell receptor , gene rearrangement , peripheral t cell lymphoma , immunology , medicine , population , cutaneous t cell lymphoma , mycosis fungoides , biology , t cell , lymphoma , microbiology and biotechnology , gastroenterology , antigen , gene , immune system , genetics , environmental health
BACKGROUND Sézary syndrome (SS) is characterized by erythroderma, peripheral lymphadenopathy, and circulating Sézary cells and is clinically heterogeneous. METHODS T‐cell receptor ( TCR ) gene analysis was performed using DNA extracted from peripheral blood mononuclear cells from 74 patients, and the results were correlated with a variety of other diagnostic parameters and patient outcomes. RESULTS Two groups were identified: 66 patients with clonal TCR gene rearrangement (clonal patients) detected with Southern blot analysis and/or polymerase chain reaction/single‐strand conformational polymorphism analysis and 8 patients with no clonal rearrangement detected (nonclonal patients) using either technique. Clonal patients were compared with nonclonal patients. The following median blood parameters were significantly greater in the clonal group: total white cell count (13.7 10 9 /L vs. 9.6 10 9 /L), lymphocyte count (4.9 10 9 /L vs. 2.2 10 9 /L), absolute Sézary count (3.22 10 9 /L vs. 0.99 10 9 /L), CD4 count (3.17 10 9 /L vs. 1.36 10 9 /L), and CD4:CD8 ratio (15.86 vs. 3.21). An expanded population of T‐cells of a specific TCR variable β subset was detected in 7 of 36 clonal patients and in 1 of 4 nonclonal patients. Cytogenetic analysis of peripheral blood from 1 nonclonal patient and 6 clonal patients was normal. The median survival from the time of diagnosis was 45 months in the clonal group, and 40 of 49 deaths were cutaneous T‐cell lymphoma (CTCL)‐related, whereas 3 deaths in the nonclonal group were unrelated to CTCL ( P < 0.01; log‐rank test). Multivariate proportional hazards analysis showed that the absolute Sézary count and lymph node status were independent prognostic variables ( P = 0.016 and P = 0.036, respectively). CONCLUSIONS TCR gene analysis defines a distinct clinicopathologic group of patients with SS. Clonal patients have a poor prognosis and are likely to die from leukemia/lymphoma, whereas nonclonal patients may have a reactive, inflammatory T‐cell disorder. The authors suggest that the definitive diagnostic criteria for patients with SS should include the presence of a clonal TCR gene rearrangement. Cancer 2001;92:1745–52. © 2001 American Cancer Society.