title: TCRgamma-chain gene rearrangement by PCR-based GeneScan: diagnostic accuracy improvement and clonal heterogeneity analysis in multiple cutaneous T-cell lymphoma samples.
abstract: Cutaneous T-cell lymphomas are a heterogeneous group of lymphomas where the tumor population emerges within a multiple subclone pattern ("clonal heterogeneity"). PCR analysis has been shown to be useful in the diagnosis of mycosis fungoides (MF) and Sézary Syndrome (SS). Focusing the attention on clonal heterogeneity, the efficacy of the multiplex/heteroduplex (HD) PCR and the GeneScan (GS) capillary electrophoresis analysis was compared in the early diagnosis of MF/SS, using a multiple sample approach. Indeed, GS demonstrated TCRgamma gene rearrangement (GR) in all the 57 SS (100%) and in 123/146 (84%) of the MF samples, whereas the multiplex/HD PCR was less sensitive. An increase in clonality was observed in connection with both a worsening of the cutaneous disease (79% T1/T2; 100% T3/T4) and an increase in the histopathological score (HS < 5, 76%; HS > or = 5, 94%). Clonal heterogeneity with adjunctive reproducible skin TCRgamma-GRs was also observed. "Clonal instability," with different GRs, was present in a small percentage of patients. Therefore, it can be concluded that GS analysis in TCRgamma-GR is able to improve diagnosis in MF/SS patients and the multiple sample approach is helpful for a correct interpretation of clonal patterns in skin lesions, especially in early-stage MF and in SS skin/blood samples.
authors.affiliation: Section of Dermatology, Department of Medical Sciences and Human Oncology, University of Turin, Turin, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Ponti
authors.forename: Maria T
authors.initials: MT
authors.lastname: Fierro
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.forename: Bonello
authors.initials: B
authors.lastname: Lisa
authors.forename: Francia di Celle
authors.initials: Fd
authors.lastname: Paola
authors.forename: Ortoncelli
authors.initials: O
authors.lastname: Michela
authors.forename: Fava
authors.initials: F
authors.lastname: Paolo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Comessatti
authors.forename: Mauro
authors.initials: M
authors.lastname: Novelli
authors.forename: Maria G
authors.initials: MG
authors.lastname: Bernengo
mesh_terms: D001706:Biopsy; D002999:Clone Cells / Q000473:pathology; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary / Q000379:methods*; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis / Q000473:pathology; D008297:Male; D009182:Mycosis Fungoides / Q000175:diagnosis* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods*; D012751:Sezary Syndrome / Q000175:diagnosis* / Q000473:pathology; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000175:diagnosis*; D013601:T-Lymphocytes / Q000473:pathology