Prognostic Significance Of The Immunophenotype In Diffuse Large B Cell Lymphoma

Background:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity of non-Hodgkin lymphomas (NHL), accounting for 30-40%of adult NHL. Although approximate 50%patients are potentially effective to anthracycline-based chemotherapy, more than half succumb to their disease with poor prognosis. Recently, the application of gene expression profiling(GEP) data had identified three distinct molecular groups:germinal centre B cell-like type(GCB), activated B cell-like type(ABC), and type 3. GCB type had the best prognosis in the three types; ABC and type 3 types had a similar poor outcome, so they were generally combined and categorized into a "non-germinal centre (non-GCB)"group. These molecular grouping reflects the biologic nature of DLBCL. Because the cDNA microarray study is expensive and requries fresh or frozen tissue, which may not be technically feasible in a clinical laboratory setting, Hans et al proposed that an immunostain panel of CD10, BCL-6 and MUM1 could be used to classify DLBCL into GCB and non-GCB, which showed prognostic significance equivalent to that of gene-expression profiling. In recent years the population of DLBCL in China has been increasing. Few studies are available about immunophenotype and prognosis in Chinese patients with DLBCL. The aims of our study were therefore, in Chinese population, to analyse the clinic, histologic and immunophenotypic characteristics of DLBCL patients, investigate their correlation to patient survival and define the applicability of identified immunohistochemical profiles. We intended to investigate more feasible and convenience parameter, to predict clinical prognosis and treatment.Materials and methods:109 cases of Chinese DLBCL diagnosed according to the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues (2008) were collected from ZheJiang Cancer Hospital. The morphologic characteristics were studied under light microscopy, and the essential immunohistochemical staining were performed. Standard two-step En Vision method of immunohistochemical staining was used to detect the expression of CD20, CD3, CD 10, MUM-1, BCL-6, BCL-2. All cases were devided into GCB group and non-GCB group according to the Hans'algorithm. Data were analyzed with X2 test, Cox proportional hazard model and Kaplan-Meier analysis by the SAS 8.2 statistical package.Result:Most of DLBCL patients were older than 40 ys, the middle age being 55 ys. The ratio of male to female was 2.21:1 approximately. Sixty-six cases (60.6%) primarily involved lymph nodes. The common extra-nodal organ involved was gastrointestinal tract (20 cases,18.3%). DLBCL patients were staged according to the Ann-Arbor Staging System.72%of patients presented at early stages (I and II), while 28%of patients at advanced stages (III and IV). The 3-year survival rate of IPI groups of low, moderate to high groups was 58.54%,28.57%, respectively. The survival analysis showed statistical significance between IPI groups low and moderate to high group. All of the 100 cases (100%) were CD3 negative and CD20 positive,68 cases (68%) were BCL-2 positive and 59 cases (59%) BCL-6 positive. CD 10 was expressed in 18 cases (18%).35 cases (35%) were MUM-1 positive. One hundred cases in this study can be classified according to Hans'algorithm.41 cases (41%) were classified as GCB subgroup, while 59 cases (59%) were non-GCB group. Non-GCB:GCB= 1.44:1.3 year-survival rate in GCB subgroup was 45.71%, while 40.00%of 3 year-survival rate in non-GCB subgroup. Life table survival analysis showed that survival status of the two subgroups according to Hans'model had no significant differences. The survival status of the BCI-6 positive group was superior to the BCL-6 negative group. There was no statistical significance in camparing survival status between BCL-2 positive group and BCL-2 negative group in GCB subgroup(p>0.05), while the survival status of BCL-2 negative group was better than BCL-2 positive group in non-GCB subgroup.Conclusion:DLBCL is a highly aggressive disease which mainly involves the middle aged population, including GCB-DLBCL and non-GCB-DLBCL subtype. The non-GCB-DLBCL is more common in Chinese NHL. The International Prognostic Index (IPI) and BCL-6 expression are independent predictors of prognosis while the expression of CD 10 and MUM-1 showes no relationship with outcome. BCL-2 expression is predictors of poor prognosis of non-GCB subgroup.