High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome (original) (raw)
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Immunohistochemical prognostic indicators of lymphoma tumors
African Journal of Biotechnology, 2009
Lymphoma, or lymphatic cancer, is a broad term encompassing a variety of cancers of the lymphatic system. This prospective study was initiated to evaluate the expression of two potential biomarkers (p53 and Cyclin D1). Lymphoma tissues were obtained from 50 patients (Royal Medical Services 1990 - 1996), which were diagnosed as Hodgkin's and NonHodgkin's lymphoma. Specimens were reassessed by examining new sections; these sections were analyzed for p53 and Cyclin D1 levels by using immunohisochemisty using formalin/paraffin embedded tissue. Results indicated that the percentages of cases exhibiting staining with p53 and Cyclin D1 were 44 and 72%, respectively. Over-expression of Cyclin D1 was near the range of reported antecedent studies, which confirm the potential oncogenic activity for Cyclin D1 in lymphoma. The expression of Cyclin D1 in both lymphoma in the same level indicates that lymphomas follow similar pathways in Jordanian population.
2003
Purpose: In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from 125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989–1994. Experimental Design: Bcl-6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl-2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method. Results: CD10 was positive in 51%, bcl-6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive...
2003
Purpose: Recent evidence has demonstrated that classical Hodgkin lymphoma (cHL) originates from mature germinal center B cells. However, only 25% of cHLs express the classical B-cell marker CD20. There is very little, and controversial, information on the prognostic significance of CD20 expression in cHL with regard to failure-free (FFS) and overall survival (OS). Experimental Design: CD20 expression was investigated in a series of 119 cases of cHL treated at a single institution where complete clinical follow-up was available. The results were correlated to FFS and OS by the Kaplan-Maier method and uniand multivariate analyses. Results: Hodgkin and Reed-Sternberg cells expressed CD20 in 20% (24 of 119) of the cases based on a cutoff of 10% positivity. Within a mean follow-up period of 12 years, univariate analysis revealed a significantly higher frequency of disease relapses in the CD20-negative group (30 of 95; 32%) compared with CD20-positive tumors (2 of 24; 8%; P 0.022). Compar...
Leukemia, 2001
Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie у15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult. Leukemia (2001) 15, 458-464.
Modern Pathology, 2011
Follicular lymphoma (FL) is one of the most common forms of the low-grade non-Hodgkin's lymphoma in adults, with a characteristic translocation, t(14;18)(q32;q21) that deregulates the expression of the BCL2 gene. The clinical course of FL patients is variable, whereby a subset of patients survive for long periods even without relapses, whereas the majority have frequent relapses with shorter survival. We have analyzed a series of 186 FLs, studying the correlation between clinical outcome and the tumor cell expression of a set of immunohistochemical markers, using an automated procedure for tissue microarrays to reduce the subjectivity of scoring. The results identified several markers associated with differences in overall survival (OS) in univariate analyses, such as Cyclin E, Mdm2, CD10, p21, IgD, Bcl-xL, CD30, and E2F6. Cases with a higher level of expression of Cyclin E, Mdm2, p21, IgD, Bcl-xL, CD30, and E2F6 were associated with a significantly shorter OS. On the other hand, strong CD10 expression was linked to a significantly better outcome. A Cox model was then constructed, integrating the Follicular Lymphoma International Prognostic Index (FLIPI) score and a restricted selection of three immunohistochemical markers: Cyclin E, Mdm2, and CD10 expression. A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients (almost 20% of the total series), with a survival probability of 100% at 5 years. This not only confirms that a group of FL cases may have a very good clinical course, but also indicates that this group can be identified using this integrated clinical and immunohistochemical approach.
Biomarkers and Prognosis in Malignant Lymphomas
Clinical Lymphoma and Myeloma, 2009
The session on follicular lymphoma (FL) began with an introductory talk on pathogenesis presented by Dr. Randy Gascoyne. Recent work from Bertrand Nadel's group has revealed that a large percentage of so-called normal individuals harbor B cells with the t(14;18) translocation, and these cells are enriched among a population of memory B cells. 1 Although not definitively established, these cells might be the harbinger of FL in at-risk individuals. The pathogenesis of FL was presented as a balance between 2 dominant influences: a genetic model in which acquired chromosomal changes that follow the t(14;18) lead to FL progression and a microenvironmental model in which stromal and immune-related cells in the tumor microenvironment influence growth and progression of FL B cells through an active crosstalk between neoplastic and non-neoplastic cells. The favored view is a combined model whereby both genetic and microenvironmental influences affect disease pace, overall survival (OS), and risk of transformation in an individual patient with FL. A possible role for host genetics that might influence both the composition and function of the immune microenvironment was discussed and led nicely into the second talk in this opening session.
CD43 Expression Is an Adverse Prognostic Factor in Diffuse Large B-Cell Lymphoma
Clinical Lymphoma and Myeloma, 2009
The CD43 molecule, also known as leukosialin, is a multifunctional type I transmembrane glycoprotein expressed in a variety of hematopoietic cells. 1 It is classified as a member of the cell-surface mucin family because of the heavily O-glycosylated extracellular domain. The evolutionary conserved intracellular domain is involved in signal transduction through activation of several signaling cascades and might regulate cell activation and proliferation. The physiologic role of CD43 was extensively studied but still remains controversial. Earlier studies on T cells suggested that CD43 is a negative regulator of T-cell function because of the rigid extracellular domain that acts as a barrier to cell-to-cell interactions. 6,7 However, more recent studies identified CD43 as the ligand for E-selectin responsible for T-cell migration to sites of inflammation. In addition, CD43 is involved in T-cell maturation and survival by promoting 10 or inhibiting apoptosis. The role of CD43 in B cells is even less clear. CD43 seems to play a role in stage and sublineage-specific maturation of precursor B cells in the bone marrow. 12 Mature plasma cells and B cells in the gastrointestinal mucosa also express this protein, but resting peripheral B cells do not. 13,14 Therefore, coexpression of CD43 and CD20 on peripheral B cells is suggestive of malignancy. 15 CD43 is differently expressed in various types of non-Hodgkin lymphomas (NHLs). Expression of CD43 in diffuse large B-cell lymphomas (DLBCLs) ranges from 16% to 28%. Diffuse large B-cell lymphoma is the most common lymphoid neoplasm, accounting for approximately 30%-40% of all NHLs. Today, about 60% of patients can be cured using a combination of anthracycline-based chemotherapy and rituximab. However, the course of individual patients varies widely, and prognostic factors are needed to distinguish patients with favorable prognosis from those who require more intensive treatment and stem cell transplantation. Currently, the most important prognostic index for Background: CD43 is a transmembrane glycoprotein expressed in different hematopoietic cells, including some subsets of B lymphocytes. About a quarter of diffuse large B-cell lymphomas (DLBCLs) express CD43, but its prognostic significance is unknown. Patients and Methods: We analyzed the prognostic effect of immunohistochemically determined CD43 expression in 119 patients with newly diagnosed DLBCL. All were treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-like chemotherapy, 57 without and 62 with rituximab. Results: A total of 31 DLBCL cases (26%) expressed CD43. Patients with CD43 + and CD43lymphomas did not differ regarding sex, International Prognostic Index (IPI) factors and score, rituximab treatment, presence of bulky disease, or germinal center subtype. Median follow-up was 45 months. Patients with CD43 + DLBCL had significantly lower complete response rates (59% vs. 80%; P = .019), 2-year event-free survival (EFS) rates (34% vs. 64%; P = .003), and overall survival (OS) rates (45% vs. 76%; P = .002). The prognostic significance of CD43 expression was retained in multivariate analysis (relative risk [RR] 2.04; P = .013 for EFS; RR 2.17; P = .016 for OS). In subgroup analysis, the effect of CD43 expression was significant in patients treated with rituximab and those with low IPI, whereas it was not reached in patients treated without rituximab. The effect was not observed in patients with high IPI. Conclusion: These results indicate that CD43 expression is an important independent adverse prognostic factor in DLBCL.