ABSTRACT
Protein kinase C-beta II (PKC-beta II) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy. This study compared prognostic significance of immunohistochemically determined PKC-beta II expression in de novo DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with and without rituximab. Outcomes were assessed in 80 consecutive patients, 48 treated with CHOP, and 32 with rituximab plus CHOP (R-CHOP). PKC-beta II expression correlated with inferior overall survival (OS) and progression-free survival (PFS) in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0-2 adverse factors), but not in the overall patient group unstratified by IPI. PKC-beta II expression correlated with inferior OS and PFS in R-CHOP-treated patients unstratified by IPI status. Immunohistochemically demonstrated PKC-beta II expression thus identified patient subgroups where alternative treatment strategies may confer superior outcome. We now report that PKC-beta II expression has prognostic significance not only for CHOP therapy in low-risk IPI disease, but also for all patients receiving CHOP plus rituximab.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/enzymology , Neoplasm Proteins/analysis , Protein Kinase C/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Gene Expression Profiling , Humans , Immunoenzyme Techniques , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Prednisolone/administration & dosage , Prognosis , Protein Kinase C beta , Rituximab , Severity of Illness Index , Survival Analysis , Treatment Failure , Vincristine/administration & dosage , Young AdultSubject(s)
Anticoagulants/administration & dosage , Coronary Artery Bypass/adverse effects , Fibrin/metabolism , Heparin/administration & dosage , Lung/blood supply , Microvessels/drug effects , Biopsy , Blood Coagulation/drug effects , Cardiopulmonary Bypass/adverse effects , Double-Blind Method , Elective Surgical Procedures , Humans , Infusions, Intravenous , Microvessels/metabolism , Partial Thromboplastin Time , Preoperative Care , Time Factors , Treatment Outcome , VictoriaSubject(s)
Antifibrinolytic Agents/adverse effects , Aprotinin/adverse effects , Fibrin/metabolism , Lung/blood supply , Microcirculation/drug effects , Thoracic Surgery , Tranexamic Acid/adverse effects , Aged , Aged, 80 and over , Case-Control Studies , Humans , Lung/drug effects , Lung/pathology , Male , Middle AgedABSTRACT
Dysfunction of proteins involved in the G1 to S transition of the cell cycle, such as p16(INK4A) and RB1, is common in many cancer types. A screen of p16 protein expression was performed in benign, borderline, and invasive ovarian tumors, together with endometrial cancers, aligned on a tissue microarray. We observed frequent p16 overexpression in serous papillary carcinomas of ovarian and endometrial origin. An extended cohort of ovarian serous papillary carcinomas was examined to further evaluate the frequency of p16 overexpression. Strong, uniform staining in the majority of cancer cells occurred commonly in invasive serous papillary ovarian cancers, particularly in grade 3 carcinomas. RB1 protein expression abnormalities were rare. Our data indicate that abnormalities in the retinoblastoma pathway, as determined by p16 overexpression, are common in serous papillary carcinomas and are probably an early event.