Affiliations: Laboratorio di Anatomia Patologica del Dipartimento di
Medicina Clinica e Sperimentale; Università del Piemonte Orientale "A.
Avogadro", Novara, Italy | Laboratorio di Patologia Molecolare del Dipartimento
di Scienze Mediche, Università del Piemonte Orientale "A. Avogadro",
Novara, Italy | Dipartimento di Oncologia, Azienda Ospedaliera San
Giovanni Battista, Torino, Italy
Note: [] Corresponding authors: Ciro Isidoro, Dipartimento di Scienze
Mediche and Guido Valente, Dipartimento di Medicina Clinica e Sperimentale,
Università "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy. Tel.:
+39 0321 660607; Fax: +39 0321 620421; E-mail: isidoro@med.unipmn.it;
valente@med.unipmn.it
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.
