T-cell receptor gamma gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome) and benign inflammatory disease: correlation with clinical, histological and immunophenotypical findings.
BACKGROUND
A dominant T-cell clone can be detected by polymerase chain reaction (PCR) in 40-90% of cutaneous samples from patients with cutaneous T-cell lymphoma (CTCL).


METHODS
From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sézary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64.5%) and CTCL in 194 (35.5%). T-cell receptor (TCR)-gamma gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T-cell lineage antigen loss, using univariate and multivariate logistic regression analyses.


OBJECTIVE
To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T-cell clonality.


RESULTS
A clonality was demonstrated in 83.5% of CTCL and in 2.3% of BID (P < 0.001). A significantly higher percentage of clonal cases was associated with the cutaneous T-score (71.4% in T1, 76.1% in T2 and 100% in nodular and erythrodermic MF samples) and with the presence of a T-cell lineage antigen loss (93.9% vs. 77.4%). Moreover, clonality was closely related to an increase in the histopathological score (51.3% in the samples with a score < 5, compared with 92% in the lesions with > or = 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score > or = 5. The multivariate logistic regression showed that the density and extent of the cell infiltrate, the degree of epidermotropism and the presence of cytological atypia share an independent predictive value for clonality in T1/T2 samples, even if the highest odds ratios (3.6) were associated with the density of the cell infiltrate. The disease course of T1/T2 patients was analysed according to the PCR findings. All the PCR-negative patients showed a long-standing stable disease course; on the other hand, a disease progression occurred in 12/87 (13.8%) positive patients.


CONCLUSIONS
The multiplex PCR/HD analysis is associated with a high diagnostic accuracy (92.7%) in CTCL patients. The finding of a clonal T-cell rearrangement is more closely associated with the histological pattern (in particular with the density and extent of the cell infiltrate) rather than with the MF cutaneous T-score or immunophenotype.
Ponti
R
R
Section of Dermatology, Department of Biomedical Sciences and Human Oncology, University of Turin, Via Cherasco 23, 10126, Torino, Italy.
Quaglino
P
P
Novelli
M
M
Fierro
M T
MT
Comessatti
A
A
Peroni
A
A
Bonello
L
L
Bernengo
M G
MG
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016009:Chi-Square Distribution; D002999:Clone Cells; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D020180:Heteroduplex Analysis; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D016015:Logistic Models; D009182:Mycosis Fungoides / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D012751:Sezary Syndrome / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D017493:Leukocyte Common Antigens