High expression of cathepsin D in non-Hodgkin's lymphomas negatively impacts on clinical outcome.
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' (>or= 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 (approximately 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 ( approximately 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.
Dipartimento di Medicina Clinica e Sperimentale, Università del Piemonte Orientale A. Avogadro, Novara, Italy.
Giuseppina
G
Nicotra
Federica
F
Manfroi
Carlo
C
Follo
Roberta
R
Castino
Nicola
N
Fusco
Claudia
C
Peracchio
Simonetta
S
Kerim
Guido
G
Valente
Ciro
C
Isidoro
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002402:Cathepsin D / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
D002402:Cathepsin D