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Disease Markers
Volume 28 (2010), Issue 3, Pages 167-183
http://dx.doi.org/10.3233/DMA-2010-0698

High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome

Giuseppina Nicotra,1,2 Federica Manfroi,1 Carlo Follo,2 Roberta Castino,2 Nicola Fusco,1 Claudia Peracchio,1,2 Simonetta Kerim,3 Guido Valente,1 and Ciro Isidoro2

1Laboratorio di Anatomia Patologica del Dipartimento di Medicina Clinica e Sperimentale; Università del Piemonte Orientale “A. Avogadro”, Novara, Italy
2Laboratorio di Patologia Molecolare del Dipartimento di Scienze Mediche, Università del Piemonte Orientale “A. Avogadro”, Novara, Italy
3Dipartimento di Oncologia, Azienda Ospedaliera San Giovanni Battista, Torino, Italy

Received 1 June 2010; Accepted 1 June 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin’s Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as ‘low expressing’ (< 20% of tumor cells) or ‘highly expressing’ (≥ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases; p = 0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases; p = 0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (~20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (~70% at 5 year). This correlation was statistically significant (log-rank test, p = 0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.