Journal of Cancer · 2026
A digital polymerase chain reaction method targeting non-recombined T-cell receptor sequences aids in diagnosing primary cutaneous T-cell lymphomas.
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Chen Chien-Chin, Wu Cheng-Lin, Tzeng Bo-Jiun, Chen Pin-Jun, Chen Wan-Li, Lim Sern Yan, Chen Yi-Ling, Chen Yi-Lin, Ho Chung-Liang, Liu Tsunglin
Аннотация
BACKGROUND: Diagnosing primary cutaneous T-cell lymphoma (PCTCL) relies on the comprehensive evaluation of clinical presentation, histopathology, immune profile, and molecular testing. Regarding molecular testing, the BIOMED-2 assay is most commonly used for detecting monoclonality of T-cell receptor (TCR) genes. However, its sensitivity is not ideal for PCTCLs, and a supplementary test is required. We recently found that the ratios of non-recombined TCR sequences J2-2P and J2-3 of the TCRβ gene were higher in T-cell lymphoma (TCL) samples than in non-TCL cases. Here, we aim to evaluate the diagnostic value of this novel biomarker for PCTCL via digital polymerase chain reaction (dPCR) as a supplementary method to the BIOMED-2 clonality assay.
METHODS: Formalin-fixed paraffin-embedded tissue samples of clinicopathologically proven PCTCL cases with a negative BIOMED-2 clonality result were retrospectively retrieved, and the clinicopathological characteristics were collected. After RNA extraction and quality checking, dPCR was performed on PCTCL specimens and control samples to quantify the J2-2P and J2-3 sequences.
RESULTS: We collected 35 skin biopsy samples from patients with early-stage PCTCL and 11 inflammatory dermatoses as controls. Ratios of the J2-2P to J2-3 concentration in controls ranged from 0.03 to 0.55% (mean ± standard deviation: 0.21 ± 0.17%). In contrast, 25 of the 35 (71.42%) PCTCL specimens exhibited J2-2P/J2-3 ratios exceeding the defined upper limit of the control group.
CONCLUSION: Our dPCR assay on the non-recombined TCRβ sequences revealed that a majority of the PCTCL cases with a negative BIOMED-2 result had higher ratios of the J2-2P to J2-3 concentration than inflammatory dermatoses. Therefore, this approach may supplement the BIOMED-2 clonality assay for diagnosing PCTCL.
METHODS: Formalin-fixed paraffin-embedded tissue samples of clinicopathologically proven PCTCL cases with a negative BIOMED-2 clonality result were retrospectively retrieved, and the clinicopathological characteristics were collected. After RNA extraction and quality checking, dPCR was performed on PCTCL specimens and control samples to quantify the J2-2P and J2-3 sequences.
RESULTS: We collected 35 skin biopsy samples from patients with early-stage PCTCL and 11 inflammatory dermatoses as controls. Ratios of the J2-2P to J2-3 concentration in controls ranged from 0.03 to 0.55% (mean ± standard deviation: 0.21 ± 0.17%). In contrast, 25 of the 35 (71.42%) PCTCL specimens exhibited J2-2P/J2-3 ratios exceeding the defined upper limit of the control group.
CONCLUSION: Our dPCR assay on the non-recombined TCRβ sequences revealed that a majority of the PCTCL cases with a negative BIOMED-2 result had higher ratios of the J2-2P to J2-3 concentration than inflammatory dermatoses. Therefore, this approach may supplement the BIOMED-2 clonality assay for diagnosing PCTCL.