Membrane PKC-beta 2 protein expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma.
The protein kinase C (PKC) plays an important role in the activation and survival of B cells. The purpose of this study was to analyze the clinical significance of PKC-beta 2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL). Tumors from 76 patients with DLBCL who received anthracycline-containing chemotherapy were examined for PKC-beta 2 protein expression by immunohistochemistry. Twenty-six cases (34%) were positive for PKC-beta 2 protein, and 50 (66%) were negative. Patients with PKC-beta-2-positive tumors showed a lower complete remission rate (31 vs 62%; P=0.015) and a lower 5-year disease-free survival (DFS) (30 vs 60%; P=0.03) than the PKC-beta-2-negative group. Overall survival (OS) was significantly lower in patients with the membranous staining pattern of PKC-beta 2 protein when compared to those with PKC-beta-2-negative tumors (14 vs 64%; P=0.005). In patients with low international prognostic index (IPI), those with tumors showing membrane expression of PKC-beta 2 had a significantly inferior DFS and OS (0 vs 79%, P=0.003; 25 vs 80%; P=0.01) compared to PKC-beta-2-negative tumors. In multivariate analysis for OS, the membrane staining of PKC-beta 2 is the strongest independent adverse prognostic factor (OR=3.4, P=0.011). Our results suggest that membrane expression of PKC-beta 2 protein on DLBCL predicts for poor survival, especially in patients with low IPI.
Espinosa
Iñigo
I
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain.
Briones
Javier
J
Bordes
Ramon
R
Brunet
Salut
S
Martino
Rodrigo
R
Sureda
Ana
A
Prat
Jaime
J
Sierra
Jorge
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology / Q000235:genetics; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics; D064546:Protein Kinase C beta; D012189:Retrospective Studies; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D011241:Prednisone