title: Immunohistochemical localization of caspase-3 correlates with clinical outcome in B-cell diffuse large-cell lymphoma.
abstract: Although B-cell diffuse large-cell lymphoma (DLCL) can respond to chemotherapy and radiotherapy, a large number of patients are still resistant to treatment. Caspase-3 is an enzyme crucial to the apoptotic process and may be important in the clinical outcome of these patients. The pattern of caspase-3 expression was studied in 54 cases of DLCL using immunohistochemistry and quantitative reverse-transcription PCR. Tumor cells displayed both a diffuse cytosolic and a punctate cytosolic staining for caspase-3. Kaplan-Meier survival curves indicated that tumor cells with a diffuse cytosolic expression of caspase-3 correlated with a poor prognosis (P > 0.0004). In addition, a punctate cellular localization was associated with complete response to treatment (P = 0.011). Cases with a small percentage of lymphoma cells expressing caspase-3 also tended to show poor survival (P > 0.09). Levels of caspase-3 mRNA were not significant (P > 0.17), although a weak trend was observed similar to the immunohistochemical analysis. The pattern of expression of caspase-3 was also assessed with respect to terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) positivity in both reactive lymph nodes and B-cell DLCL cases. Our results suggest that TUNEL-positive cells are not caspase-3-positive and that there is no correlation between DLCL cases with a high degree of DNA fragmentation and caspase-3 immunostaining. Furthermore, a survival curve indicated that a high TUNEL positivity was associated with a poor survival probability (P < 0.02) and a poor response to treatment (P = 0.04). These results confirm the dynamic nature of caspase-3 expression in DLCL and suggests that the pattern of expression of the enzyme has prognostic significance.
authors.affiliation: Department of Pathology, Leicester Royal Infirmary, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Donoghue
authors.forename: H S
authors.initials: HS
authors.lastname: Baden
authors.forename: I
authors.initials: I
authors.lastname: Lauder
authors.forename: S
authors.initials: S
authors.lastname: Sobolewski
authors.forename: J H
authors.initials: JH
authors.lastname: Pringle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008198:Lymph Nodes / Q000201:enzymology; D016393:Lymphoma, B-Cell / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases