The Clinical Significance of CD10 Antigen Expression
The Clinical Significance of CD10 Antigen Expression
The clinical significance and prognostic value of CD10 in de novo diffuse large B-cell lymphoma (DLBCL) is largely unknown. We retrospectively studied 19 men and 9 women based on the following criteria: (1) DLBCL with no evidence of concomitant or antecedent follicular lymphoma; (2) available flow cytometric immunophenotyping data, including CD10 status; (3) older than 15 years; (4) specific exclusion of high-grade, Burkitt-like lymphoma; and (5) exclusion of primary cutaneous DLBCL. When available, clinical data at diagnosis, including components of the international prognostic index, were reviewed. Eleven cases were CD10+, and 17 were CD10-. There was no significant difference between the CD10+ and CD10- groups in age, sex, stage, performance status, extranodal involvement, or serum lactate dehydrogenase levels at diagnosis. However, in the 26 cases for which follow-up data were available, the CD10+ group displayed a shorter overall survival than the CD10- group (8 vs 30 months). Although the clinical findings at diagnosis are similar in CD10+ and CD10- DLBCL, CD10 expression is associated with shortened overall survival. Therefore, our data suggest CD10 expression may have prognostic importance in adults with de novo DLBCL.
Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% to 40% of newly diagnosed non-Hodgkin lymphomas in the United States. Morphologically, this entity is characterized by a diffuse proliferation of large lymphoid cells with vesicular nuclei and prominent nucleoli. It represents a clinically and histologically diverse group of lymphomas, which includes diffuse centroblastic and immunoblastic B-cell lymphoma in the Kiel classification and malignant lymphoma, diffuse large cell, and immunoblastic types in the Working Formulation. In the Revised European-American Lymphoma (REAL) and upcoming World Health Organization classifications, diffuse large B-cell lymphomas are not subclassified further and include cases previously classified as immunoblastic lymphoma. This category also comprises de novo DLBCLs and those transformed from low-grade B-cell lymphomas.
In general, DLBCL is an aggressive disease with a median survival of 1 to 2 years if untreated. Standard systemic chemotherapy generally includes doxorubicin-containing regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and produces complete remission in 50% to 60 % of cases. Several attempts to improve therapy of the intermediate- and high-grade lymphomas during the past 20 years have been based largely on empiric changes in the treatment regimens. However, randomized trials have not confirmed any sig-
nificant improvement compared with CHOP, and, overall, only one third of the patients with high-stage disease are cured.
Several clinical factors have prognostic significance in DLBCL, including age, stage of the disease, systemic symptoms, performance status, tumor burden, and serum lactate dehydrogenase (LDH) levels, all of them essentially incorporated into the international prognostic index (IPI). The IPI was developed for patients with intermediate- and high-grade non-Hodgkin lymphomas as defined in the Working Formulation and successfully predicts outcome based on the patients' clinical characteristics before treatment.
In contrast, biologic markers (histologic type, immunophenotype, and genetic findings) have not been reliable for predicting the outcome in patients with DLBCL. Histologic subclassification of DLBCL has been problematic owing to lack of reproducible criteria. The attempts to link certain immunophenotypic and genetic findings with different clinical outcome have provided controversial results. Anecdotal studies have found that the absence of CD20, CD22, or HLA-DR correlated with poorer survival, and CD24 expression or lack of CD38 was associated with better relapse-free survival in patients with DLBCL. More aggressive clinical course and more frequent bone marrow involvement was observed in CD5+ compared with CD5- DLBCL. CD44v6, an isoform of the CD44 adhesion molecule involved in cell-cell interactions and metastasis, emerged as a significant parameter for poorer overall survival in the patients with primary nodal DLBCL as reported by Inagaki et al. In another study, evaluation of the proliferative index did not explain the differences in outcome between patient groups defined by the IPI. Conflicting results are reported on the clinical significance of bcl-2, bcl-6, and c-myc oncogenes and tumor suppressor gene p53 in DLBCL. Recently, distinct types of DLBCL based on gene expression profiling were identified.
CD10, the common acute lymphoblastic leukemia antigen (CALLA), is a single-chain, 100-kd glycoprotein with a sequence identical to that of neutral endopeptidase. CD10 might have a role in inactivating regulatory peptides favoring differentiation events. In normal lymphoid ontogeny, CD10 is expressed on pro-B cells and also on mature germinal center B cells. Approximately 75% of precursor B-cell acute lymphocytic leukemias express CD10. CD10 is also present in a majority of follicular lymphoma and small noncleaved (Burkitt and high-grade Burkitt-like) lymphoma. It is useful for separating follicular from other low-grade B-cell lymphomas. Approximately 20% to 30% of de novo DLBCLs express the CD10 antigen. Previous studies have examined the prognostic value of other possible markers of follicle center differentiation in DLBCL, but the clinical significance of CD10 in DLBCL is largely unknown. Only a few reports on its prognostic relevance have emerged in the literature, without a clear consensus. Our aim was to study the prognostic value of CD10 in de novo DLBCL by examining the relationship of CD10 expression to the components of the IPI and to overall survival.
The clinical significance and prognostic value of CD10 in de novo diffuse large B-cell lymphoma (DLBCL) is largely unknown. We retrospectively studied 19 men and 9 women based on the following criteria: (1) DLBCL with no evidence of concomitant or antecedent follicular lymphoma; (2) available flow cytometric immunophenotyping data, including CD10 status; (3) older than 15 years; (4) specific exclusion of high-grade, Burkitt-like lymphoma; and (5) exclusion of primary cutaneous DLBCL. When available, clinical data at diagnosis, including components of the international prognostic index, were reviewed. Eleven cases were CD10+, and 17 were CD10-. There was no significant difference between the CD10+ and CD10- groups in age, sex, stage, performance status, extranodal involvement, or serum lactate dehydrogenase levels at diagnosis. However, in the 26 cases for which follow-up data were available, the CD10+ group displayed a shorter overall survival than the CD10- group (8 vs 30 months). Although the clinical findings at diagnosis are similar in CD10+ and CD10- DLBCL, CD10 expression is associated with shortened overall survival. Therefore, our data suggest CD10 expression may have prognostic importance in adults with de novo DLBCL.
Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% to 40% of newly diagnosed non-Hodgkin lymphomas in the United States. Morphologically, this entity is characterized by a diffuse proliferation of large lymphoid cells with vesicular nuclei and prominent nucleoli. It represents a clinically and histologically diverse group of lymphomas, which includes diffuse centroblastic and immunoblastic B-cell lymphoma in the Kiel classification and malignant lymphoma, diffuse large cell, and immunoblastic types in the Working Formulation. In the Revised European-American Lymphoma (REAL) and upcoming World Health Organization classifications, diffuse large B-cell lymphomas are not subclassified further and include cases previously classified as immunoblastic lymphoma. This category also comprises de novo DLBCLs and those transformed from low-grade B-cell lymphomas.
In general, DLBCL is an aggressive disease with a median survival of 1 to 2 years if untreated. Standard systemic chemotherapy generally includes doxorubicin-containing regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and produces complete remission in 50% to 60 % of cases. Several attempts to improve therapy of the intermediate- and high-grade lymphomas during the past 20 years have been based largely on empiric changes in the treatment regimens. However, randomized trials have not confirmed any sig-
nificant improvement compared with CHOP, and, overall, only one third of the patients with high-stage disease are cured.
Several clinical factors have prognostic significance in DLBCL, including age, stage of the disease, systemic symptoms, performance status, tumor burden, and serum lactate dehydrogenase (LDH) levels, all of them essentially incorporated into the international prognostic index (IPI). The IPI was developed for patients with intermediate- and high-grade non-Hodgkin lymphomas as defined in the Working Formulation and successfully predicts outcome based on the patients' clinical characteristics before treatment.
In contrast, biologic markers (histologic type, immunophenotype, and genetic findings) have not been reliable for predicting the outcome in patients with DLBCL. Histologic subclassification of DLBCL has been problematic owing to lack of reproducible criteria. The attempts to link certain immunophenotypic and genetic findings with different clinical outcome have provided controversial results. Anecdotal studies have found that the absence of CD20, CD22, or HLA-DR correlated with poorer survival, and CD24 expression or lack of CD38 was associated with better relapse-free survival in patients with DLBCL. More aggressive clinical course and more frequent bone marrow involvement was observed in CD5+ compared with CD5- DLBCL. CD44v6, an isoform of the CD44 adhesion molecule involved in cell-cell interactions and metastasis, emerged as a significant parameter for poorer overall survival in the patients with primary nodal DLBCL as reported by Inagaki et al. In another study, evaluation of the proliferative index did not explain the differences in outcome between patient groups defined by the IPI. Conflicting results are reported on the clinical significance of bcl-2, bcl-6, and c-myc oncogenes and tumor suppressor gene p53 in DLBCL. Recently, distinct types of DLBCL based on gene expression profiling were identified.
CD10, the common acute lymphoblastic leukemia antigen (CALLA), is a single-chain, 100-kd glycoprotein with a sequence identical to that of neutral endopeptidase. CD10 might have a role in inactivating regulatory peptides favoring differentiation events. In normal lymphoid ontogeny, CD10 is expressed on pro-B cells and also on mature germinal center B cells. Approximately 75% of precursor B-cell acute lymphocytic leukemias express CD10. CD10 is also present in a majority of follicular lymphoma and small noncleaved (Burkitt and high-grade Burkitt-like) lymphoma. It is useful for separating follicular from other low-grade B-cell lymphomas. Approximately 20% to 30% of de novo DLBCLs express the CD10 antigen. Previous studies have examined the prognostic value of other possible markers of follicle center differentiation in DLBCL, but the clinical significance of CD10 in DLBCL is largely unknown. Only a few reports on its prognostic relevance have emerged in the literature, without a clear consensus. Our aim was to study the prognostic value of CD10 in de novo DLBCL by examining the relationship of CD10 expression to the components of the IPI and to overall survival.
