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. 2013 Apr 19;3(4):e111.
doi: 10.1038/bcj.2013.10.

Loss of TCR-beta F1 and/or EZRIN expression is associated with unfavorable prognosis in nodal peripheral T-cell lymphomas

S M Rodríguez-Pinilla  1 , M E C Sánchez, J Rodríguez, J F García, B Sánchez-Espiridión, L F Lamana, G Sosa, J C Rivero, J Menárguez, I B Gómez, F I Camacho, P R Guillen, C P S Orduña, G Rodríguez, C Barrionuevo, R Franco, M Mollejo, J F Marco, R D de Otazu, M A Piris
Affiliations

Loss of TCR-beta F1 and/or EZRIN expression is associated with unfavorable prognosis in nodal peripheral T-cell lymphomas

S M Rodríguez-Pinilla et al. Blood Cancer J. .

Abstract

Nodal peripheral T-cell lymphoma (nodal PTCL) has an unfavorable prognosis, and specific pathogenic alterations have not been fully identified. The biological and clinical relevance of the expression of CD30/T-cell receptor (TCR) genes is a topic under active investigation. One-hundred and ninety-three consecutive nodal PTCLs (89 angioimmunoblastic T-cell lymphomas (AITL) and 104 PTCL-unspecified (PTCL-not otherwise specified (NOS)) cases) were analyzed for the immunohistochemical expression of 19 molecules, involving TCR/CD30 pathways and the associations with standard prognostic indices. Mutually exclusive expression was found between CD3 and TCR-beta F1 with CD30 expression. Taking all PTCL cases together, logistic regression identified a biological score (BS) including TCR molecules (TCR-beta F1 and EZRIN) that separates two subgroups of patients with a median survival of 34.57 and 5.20 months (P<0.001). Multivariate analysis identified BS and the prognostic index for PTCL (PIT) score as independent prognostic factors. This BS maintained its significance in multivariate analysis only for the PTCL-NOS subgroup of tumors. In AITL cases, only a high level of ki67 expression was related to prognosis. A BS including molecules involved in the TCR signaling pathway proved to be an independent prognostic factor of poor outcome in a multivariate analysis, specifically in PTCL-NOS patients. Nevertheless, validation in an independent series of homogeneously treated PTCL patients is required to confirm these data.

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Figures

Figure 1
Figure 1
Representative pictures of nodal PTCL expressing CD3 (a), TCR-beta F1 (b) and EZRIN (c). Nodal PTCL cases negative for CD3 (d), TCR-beta F1 (e) and EZRIN (f). Nodal PTCL expressing low levels of CD30 (g). Nodal PTCL cases positive for JUNB (h) and BLIMP1 (i). A representative AITL case expressing both PD1 (j) and Caveolin-1 (k). Nodal PTCL case showing a high level of KI67 expression (l).
Figure 2
Figure 2
Univariate Kaplan–Meier survival curves of significant prognostic clinical indices in the present series of nodal PTCL cases.
Figure 3
Figure 3
Univariate Kaplan–Meier survival curves of significant biological markers.
Figure 4
Figure 4
(a) Univariate Kaplan–Meier survival curves of the BS created on the basis of the combination of biological variables that were significant in the Cox multivariate analysis (EZRIN and TCR-beta F1) in nodal PTCL patients. (b) Univariate Kaplan–Meier survival curves of the BS created on the basis of the combination of biological variables that were significant in the Cox multivariate analysis (EZRIN and TCR-beta F1) in PTCL-NOS patients.
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