Clinical relevance of the expression of the CD31 ligand for CD38 in patients with B-cell chronic lymphocytic leukemia

BACKGROUND: CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]) is the ligand for CD38, a transmembrane glycoprotein that is expressed on the surface of leukemic cells in many patients with B-cell chronic lymphocytic leukemia (B-CLL). In a previous study, the authors showed that CD38 expression was correlated with a poor prognosis in patients with B-CLL. In the current study, blood samples from patients with B-CLL were examined to identify CD31 surface marker expression, and CD31 expression was correlated with several other known prognostic variables, including CD38. METHODS: Using flow cytometry, peripheral blood samples from 120 patients with B-CLL were analyzed for CD31 and CD38 expression on CD19 positive leukemic B cells. RESULTS: Thirteen of 120 patients (11%) had CD31 expression on < 20% of their B cells, and the remaining patients had various levels of CD31 expression. The median expression of CD31 was 76% of leukemic, CD19 positive cells. Levels of CD31 expression were not correlated with survival outcomes or with any of the known prognostic parameters when all patients were considered. Patients who had high CD38 expression (>or= 20%), as expected, had significantly shorter survival (P = 0.001) compared with patients who had low CD38 expression (< 20%). However, in patients with low CD38 expression, a subgroup with low CD31 expression (< 76%) had significantly longer survival compared with the survival for the entire group (P = 0.0001). Moreover, the survival pattern of patients with low CD38 expression and high CD31 expression was not significantly different from the survival pattern seen in patients with high CD38 expression. CONCLUSIONS: CD31 expression further defined a subgroup of patients with B-CLL who had a different survival outcome. Defining the interaction between CD31 expression and CD38 expression in patients with CLL will require further exploration.     

Serum BAFF levels are related to angiogenesis and prognosis in patients with multiple myeloma

B-cell activating factor (BAFF) is a B-cell growth factor. We measured its serum levels and correlated them with parameters of disease activity, as serum levels of tumor necrosis factor-α and lactate dehydrogenase, bone marrow microvascular density and proliferating cell nuclear antigen expression, in 50 myeloma patients, in 22 of them in plateau phase and in 20 controls. All of them were higher in patients and in advanced disease while reduced in plateau phase. BAFF correlated with all the above markers. Higher BAFF levels predicted a shorter survival, suggesting an important prognostic marker and a possible therapeutic target in myeloma.     

Autologous Bone Marrow Transplantation in Multiple Myeloma: A Single Centre Experience of 23 Patients

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).     

The Prognostic Significance of the CD34 Antigen in Acute Myeloid Leukaemia

The prognostic value of CD34 expression on leukaemic blast cells was assessed in 38 patients with acute myeloid leukaemia. Nineteen patients had more than 10% CD34 positive blast cells. Median survival for the CD34 positive patients was 125 days and for the CD34 negative patients the median survival has not yet been reached at day 575 (p = 0.06). Of those patients who received intensive chemotherapy, CD34 positive patients (n = 13) had a median survival of 150 days while for CD34 negative patients (n = 14) the median survival has not yet been reached (p = 0.01). Adjustment for age and pre-existing myelodysplastic syndrome did not affect the correlation of CD34 positivity with survival (p = 0.02). Over the period of observation (median 10 months, range 2-19 months) the relative risk of death was 5 times greater for the CD34 positive patients.

This study suggests that CD34 expression is an adverse prognostic marker, independent of age and pre-existing myelodysplasia.     

The prognostic significance of the CD34 antigen in acute myeloid leukaemia.

The prognostic value of CD34 expression on leukaemic blast cells was assessed in 38 patients with acute myeloid leukaemia. Nineteen patients had more than 10% CD34 positive blast cells. Median survival for the CD34 positive patients was 125 days and for the CD34 negative patients the median survival has not yet been reached at day 575 (p = 0.06). Of those patients who received intensive chemotherapy, CD34 positive patients (n = 13) had a median survival of 150 days while for CD34 negative patients (n = 14) the median survival has not yet been reached (p = 0.01). Adjustment for age and pre-existing myelodysplastic syndrome did not affect the correlation of CD34 positivity with survival (p = 0.02). Over the period of observation (median 10 months, range 2-19 months) the relative risk of death was 5 times greater for the CD34 positive patients. This study suggests that CD34 expression is an adverse prognostic marker, independent of age and pre-existing myelodysplasia.     

Association of CD38 antigen expression with other prognostic parameters in early stages of chronic lymphocytic leukemia

The expression of the surface molecule CD38 on B cell chronic lymphocytic leukemia (B-CLL) cells has recently been described as a prognostic marker for patient survival. We have analyzed CD19/CD38 expression in 81 patients with predominantly early stages of B-CLL (69 Binet A, seven Binet B, five Binet C). Sixty-two patients (77%) had less than 30% CD38+/CD19+ cells, while 19 (23%) had > or = 30%. There was a significant association between Binet stages (A vs. B+C, p < 0.0001), Rai stages (0-II vs. III+IV, p < 0.001) and CD38 expression, confirming the published cut-off level of 30%. A particularly strong association between CD38 expression was found with soluble CD23 (sCD23) levels of > or = 2000 U/ml (p < 0.0001) and beta2-microglobulin (beta2 MG) serum levels of > or = 3 mg/l (p < 0.0001) indicating that CD38 is a marker of tumor mass as well as disease progression. A borderline association was found with lymphocyte doubling time (LDT) < 12 months (p = 0.05) due to low patient numbers, while there was no association with age, sex or immunoglobulin deficiency. Discordant results were obtained in a number of patients: 10 of 69 patients (14%) with Binet A had a CD38 > or = 30% while three of seven patients with Binet B had a CD38 < 30%. In these two subgroups CD38 and other prognostic factors gave discrepant results. Due to the early stage and short median observation time (12 months. range 1-24 months), calculations concerning patient survival were not performed. However, our data show a strong association between CD38 and other known prognostic factors. The results also suggest that this factor is not always reliable in Binet A patients.     

CD38 as a prognostic factor in Chinese patients with chronic lymphocytic leukaemia

B-cell chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the Western countries, however, infrequent in the Eastern. It shows a remarkable heterogeneity, with some patients having an almost normal lifespan, others surviving only several years after diagnosis despite intensive therapy. To explore the prognostic significance of CD38 expression in Chinese patients with CLL, multi-parameter flow cytometry was used to detect the expression of CD38 on CD5(+)CD19(+) cells of 147 patients. CD38 expression and its association with some other prognostic factors such as Binet stage, lymphocyte count in peripheral blood, serum lactate dehydrogenase (LDH), beta2-microglobulin (beta2-MG), ZAP-70 expression and cytogenetic abnormalities were analyzed. The Kaplan-Meier method was used to construct survival curves, and results were compared using the log-rank test. Univariate and multivariate Cox regression analyses were used to assess associations between survival time and potential risk factors. Out of the 147 CLL patients, positive expression of CD38 was found in 45 (30.6%) cases. CD38-positivity identified a subgroup of CLL patients with aggressive disease of Binet stage at the time of the test (P=0.036). Furthermore, the presence of higher serum LDH and beta2-MG levels at diagnosis was strongly correlated with CD38-positive (P=0.016 and 0.025, respectively). Prognostically unfavorable cytogenetic abnormalities, including 17p13 and 11q22 deletions, were significantly more frequent in CD38-positive patients than in CD38-negative ones (P=0.047 and 0.001, respectively). There was no significant difference between CD38-positive and CD38-negative groups in molecular cytogenetic aberrations of del(6q23), del(13q14), 14q32 translocation, or trisomy 12. In addition, in CD38-positive patients, the percentage of leukemic cells expressing ZAP-70 protein was not significantly higher than in CD38-negative ones (P=0.120). CD38 expression was associated with poor outcome. Patients with positive expression of CD38 had significantly shorter overall survival (mean, 81 months) than patients without CD38 expression (mean, 179 months) (P=0.015). Univariate analysis showed that serum levels of LDH and beta2-MG, del(17p13) and CD38 expression were the significant factors in determining overall survival (OS). Del(17p13) and CD38 expression were the variables strongly associated with OS by multivariate Cox regression analysis. It was showed that the patients with high level of CD38 expression had poorer outcome; CD38 was a good predictor of OS in Chinese patients with CLL.     

Clinical significance of telomerase activity in multiple myeloma

BACKGROUND: The clinical course of patients with multiple myeloma varies, and therefore it is important to evaluate the disease state. We studied the telomerase activity of myeloma cells as a possible prognostic factor in such patients. METHODS: Twenty five samples from patients with multiple myeloma were studied. We purified myeloma cells in bone marrow samples according to the expression of surface antigens, CD38 and CD45. CD38+/CD45- or dim cells had morphologic characteristics of myeloma cells, with a purity exceeding 95%. The telomerase activity of myeloma cells was determined by a polymerase chain reaction-based telomeric repeat amplification protocol assay. Ki-67 positivity of the purified cells was determined by flow cytometry using anti-Ki-67 antibody. The relationship between telomerase activity and prognostic factors was also examined. RESULTS: A significantly high degree of telomerase activity was detected in subjects with a serum beta2-microglobulin level > or = 6 mg/dL or at Stage III (P = 0.002). The serum C-reactive protein, lactate dehydrogenase, and creatinine levels did not correlate with the telomerase activity, but this activity did significantly correlate with Ki-67 positivity and the percentage of plasma cells in the bone marrow (r = 0.561, P = 0.004, and r = 0.397, P = 0.049, respectively). The patients with high levels of telomerase activity were thus found to have a significantly short survival time after sampling (P = 0.035). CONCLUSIONS: The measurement of the telomerase activity in myeloma cells was found to be a reliable marker for the proliferating capacity and tumor mass in myeloma patients. The telomerase activity of myeloma cells may therefore be useful as a prognostic factor.     

Preoperative elevation of serum C--reactive protein is predictive for prognosis in myeloma bone disease after surgery

We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n=71) were compared between patients with preoperative CRP>or=6 mg l-1 and those with CRP<6 mg l-1. Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l-1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease.     

Does Immunohistochemistry Provide Additional Prognostic Data in Gastrointestinal Stromal Tumors?

Background: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical(IHC) features in patients with gastrointestinal stromal tumours (GISTs). Materials and Methods: Fifty-sixpatients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationshipsbetween clinicopathologic/immunohistochemical factors and prognosis were investigated. Results: Medianoverall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 monthsin resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology wassignificantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours weresignificantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tendedto survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7months vs 15.9 months; p=0.002). High Ki-67 level (≥30%) was significantly associated with shorter OS (34 vs95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours(Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours;(50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosisof GISTs. Multivariate analysis demonstrated that ≥10/50HPF mitotic activity/HPF was the only independentfactor for risk of death in GIST patients. Conclusions: Despite the negative prognostic and predictive effect ofhigh Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMApositivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required toprovide supportive data for these findings.     

Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion.

Studies of bortezomib in patients with relapsed multiple myeloma (MM) suggested that bortezomib may be active even in the presence of adverse prognostic factors. We therefore evaluated 62 patients with relapsed/refractory MM who were treated with single-agent bortezomib, and addressed the question whether or not the negative prognostic impact of unfavorable cytogenetic abnormalities may be overcome by bortezomib. By interphase fluorescence in situ hybridization (FISH), a deletion of chromosome 13q14 [del(13q14)] was present in 33 patients (53%). Overall response rates to bortezomib were similar in patients with and without del(13q14) (45 versus 55%; P=0.66), and rates of complete remission (CR) near CR were also not different between the two patient populations (18 versus 14%). Three patients had a t(4;14)(p16;q32) in addition to del(13q14), and all of them had a >50% paraprotein reduction. Median duration of response was 12.3 months in patients with del(13q14) compared with 9.3 months in patients with normal 13q-status (P=0.25), and survival was also not different between the two patient populations. Patients not benefiting from single-agent bortezomib were characterized by the combined presence of a del(13q14) and low serum albumin (median survival 4.6 months). Our results provide evidence for remarkable activity of bortezomib in MM with del(13q14). Patients who do not respond to bortezomib and consecutively have short time to treatment failure and overall survival can be identified by low serum albumin in addition to del(13q14) and should be considered for bortezomib combinations.     

Concentration of free hCGbeta subunit in serum as a prognostic marker for squamous-cell carcinoma of the oral cavity and oropharynx.

This study was conducted to evaluate the clinical usefulness of serum hCGbeta in the diagnosis and prognosis of patients (n = 59) with cancers of the oral cavity and oropharynx. As a reference marker we used squamous-cell carcinoma antigen (SCCAg). A blood sample was obtained from all patients before primary surgery. Serum hCGbeta was determined by a time-resolved immunofluorometric assay (IFMA) and SCCAg by a solid phase immunoenzymometric assay. Elevated preoperative hCGbeta levels were observed in 8 (14%) and elevated SCCAg in 12 (20%) out of 59 patients. Patients with preoperatively elevated hCGbeta had a shorter recurrence-free survival when compared with those with normal hCGbeta levels (log-rank Chi-squared = 6.83, p =.009), and the risk-ratio for recurrence during follow-up for those was 3.6 (95% CI = 1.29-9.94). In a Cox multivariate model hCGbeta (p = 0.039) and stage (p = 0.044) were independent prognostic factors. SCCAg showed no correlation with recurrence-free survival. We conclude that determination of hCGbeta in serum is a potential marker in the prognostic evaluation of patients with SCC of the oral cavity and oropharynx.     

沙利度胺治疗132例初诊时伴或不伴髓外病变多发性骨髓瘤的疗效比较

 【摘要】　目的　分析沙利度胺治疗初诊时伴或不伴髓外病变（EM）的多发性骨髓瘤（MM）患者的疗效及对预后的影响。方法　回顾性分析132例MM患者的临床特点及其预后相关因素,分析沙利度胺对伴或不伴EM的MM患者的疗效及对预后的影响。结果　132例患者中位年龄59岁（28～83岁）,其中52例（39.4 %）伴EM;80例（60.6 %）不伴EM。伴EM患者预计总生存（OS）时间为42.5个月,不伴EM患者为54.3个月,差异有统计学意义（P＝0.004）。所有患者中,服用沙利度胺的MM患者预计OS较未服用者长（50.7个月比41.2个月）,差异有统计学意义（P＝0.01）;对于EM患者,是否服用沙利度胺对患者预后差异无统计学意义（39.7个月比38.5个月,P＝0.491）,而对初诊时不伴EM的MM患者,服用沙利度胺的患者预后明显优于未服用者（54.6个月比41.2个月,P＝0.027）。单因素分析显示初诊时伴EM（P＝0.004）、浆细胞比例≥20 %（P＝0.02）、血红蛋白≤110 g／L（P＝0.041）、β2微球蛋白（β2-MG）≥5.5 mg／L（P＝0.018）及未服用沙利度胺（P＝0.01）为预后不良指标;COX多因素分析显示,EM、β2-MG以及浆细胞比例为本组患者的独立预后因素（P＜0.05）。结论　初诊时伴EM患者较不伴EM者预后差,沙利度胺不能改善伴EM患者的预后,可能需要联合硼替佐米等新药或进行自体造血干细胞移植。     

Isolated paraaortic lymph-node recurrence after the curative resection of colorectal carcinoma

BACKGROUND AND OBJECTIVES: Isolated paraaortic lymph-node recurrence (IPLR) after curative surgery for colorectal carcinoma is rare and no previous report has specifically addressed this type of recurrence. We investigated the clinical features of IPLR and analyzed prognostic factors. METHODS: Of 2,916 patients who underwent curative surgery for colorectal carcinoma, IPLR was identified in 38 patients (1.3%). The clinical features and prognostic factors of these patients were analyzed. RESULTS: IPLR was first detected by increased serum carcinoembryonic antigen (CEA) levels (63.2%) or by routine follow-up computed tomography (CT) (36.8%). Curative resection of IPLR was performed in six patients (15.8%). A total of 19 patients (50.0%) received chemoradiation therapy and 13 patients (34.2%) received chemotherapy only. The median survival from IPLR was 13 months (range: 5-60 months). The median survival time from IPLR for the resected patients was 34 months, whereas it was 12 months for those who did not undergo resection (P = 0.034). The factors associated with the prognosis were histological grade (P = 0.003), location (P = 0.032), and resection of IPLR (P = 0.034). CONCLUSIONS: IPLR after curative surgery for colorectal carcinoma is rare. Although it is generally associated with poor prognosis, better survival might be achieved through curative resection in selected cases.     

Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer

BACKGROUND: The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival. RESULTS: One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (> or =20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively. In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival. CONCLUSIONS: CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC.     

MUM1/IRF4 expression is an unfavorable prognostic factor in B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

B-Cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL / SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV(H)), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = 0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV(H) status were independent unfavorable prognostic factors in patients with B-CLL / SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL / SLL. The biological role and mechanism of action of MUM1 in B-CLL / SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.     

Decreased HDL-Dependent Paraoxonase and Arylesterase Enzyme Activity May Indicate a Worse Prognosis in Multiple Myeloma

Background: Multiple myeloma (MM) is a haematological cancer characterized by clonal proliferation ofplasma cells.The aim of this study was to investigate the activity of serum paraoxonase-1 (PON1) and arylesterase(ARE) in multiple myeloma with and without free light chain excretion(FLCe-MM and NFLCe-MM); as wellas to investigate possible alterations in oxidative stress parameters. Materials and Methods: Total thiol (T.thl),oxidative stress index (OSI), total oxidant status (TOS) and total antioxidant status (TAS) were examined inaddition to the PON1 and ARE enzyme activities in twenty one FLCe-MM and nineteen NFLCe-MM subjects.Routine parameters like lipid panel, serum total protein, albumin, creatinine, blood urea nitrogen (BUN), uricacid and hemoglobin levels were compared with the oxidative stress markers. Results: Serum total protein, BUN,creatinin, and uric acid levels were significantly higher (p=0.04, p=0.001, p=0.001 and p=0.0022, respectively), whilehemoglobin and albumin levels were significantly lower in FLCe-MM patients (p=0.009 and p=0.04,respectively).PON1 and ARE activities were significantly lower in patients with FLCe-MM compared to those with NFLCe-MM (p=0.001 and p=0.008, respectively). Conclusions: Depending on our results of prognostic markers of MMsuch as age, hemoglobin, albumin, and creatinine we feel confident to presume FLCe-MM as a subgroup witha worse prognosis. A decrease in PON1 and ARE activities may contribute to the prognosis and may be used asa prognostic tool in MM.     

The roles of chemotherapy and surgery in gastric carcinoma and the influence of prognostic factors on survival

In this study, we present the results of surgery and chemotherapy and the impact of various prognostic factors on survival in patients with gastric carcinoma with a follow-up of 6 years. All of the 328 cases were adenocarcinoma histologically and had a median age of 55 years. Median survival was 11 months, and the 5-year survival rate was 18%. Nonmetastatic cases were associated with improved survival as compared with the cases with metastatic disease (p<0.001). Patients with gastrectomy had improved survival (p<0.001). Subtotal gastrectomized patients had better survival rates in comparison to the total gastrectomized patients (p = 0.03). Addition of splenectomy to total gastrectomy and adjuvant chemotherapy did not influence survival rates (p>0.05). In metastatic patients, we determined beneficial effects of gastrectomy and chemotherapy on survival. The benefit was most predominant in chemoresponsive patients (p<0.001). Higher serum CA 19.9 levels in patients without metastases, higher serum lactate dehydrogenase and carcinoembryonic antigen levels in patients with metastases, and lower serum albumin levels in both stages were determined as significant predictors of poor survival. On multivariate analysis, only higher serum CA 19.9 level was the independent unfavorable prognostic factor of survival time in nonmetastatic patients (p = 0.008). In metastatic disease, older age (p = 0.03) and male gender (p = 0.05) were associated with poorer survival. In conclusion, gastric cancer is a great health problem, especially in developing countries, and we need more optimal approaches and treatment modalities for gastric cancer.     

Complex Immunophenotypic Changes as Prognosis Panel in Chronic Lymphocytic Leukemia

The present study proposes to asses the prognosis with consecrated markers CD38 and the new ZAP-70 related to the various patterns of CLL complex immunophenotype: cyclin D1, CD38, CD20, FMC7, CD23. This particular combination could be used as a prognosis panel in CLL.Brief AbstractBackgroundChronic lymphocytic leukemia (CLL) has many other prognostic markers established in the past years related to disease and to the patient status, and the most important seem to now be immunophenotypical, genetic, and molecular. CD38 and ZAP-70 are now used in a strong prognosis panel of markers for CLL.AimsThe present study proposes to assess the prognosis with consecrated markers CD38 and the new ZAP-70 related to the various patterns of CLL immunophenotype.Patients and MethodsWe have analyzed 187 patients diagnosed with CLL in order to find correlations between clinical stage, immunophenotype, and outcome.ResultsWe found correlations between expression of CD38 related to clinical outcome, (dr: 0.541; P < .05.), and between ZAP-70 and CD38 (dr: 0.666; P = .018). The expression of BCL-2 was correlated to outcome (dr: 0.533; P < .01) and response to treatment (dr: 0.420; P < .01). Cyclin D1 expression was found in correlation with outcome (P = .014) and BCL-2 expression (P = .034). Lower expression CD23 was associated with poor outcome and expression of CD38 and ZAP-70 (P value < .05; dr: —0.117). We found in patients with cyclin D1 positive comparative to those cyclin D1 negative the association of high intensity CD20⁺ (28% vs. 3%), FMC7⁺ (33% vs. 8%), and lower CD23 (30%-60% vs. > 60%). Also, CD38 was positive in 44% vs. 10% and ZAP-70 in 66% versus 5%. This association defines a “lymphoma”-like immunophenotype for cyclin D1—positive cases. Treatment was chlorambucil, fludarabine/cyclophosphamide (FC), or FC + rituximab (FCR).ConclusionFlow cytometry is the most practical method used in CLL for diagnosis and prognosis evaluation. The immunophenotypical markers surrogate for IgVH mutation status, as CD38 and ZAP-70 have a strong correlation with outcome in CLL, and our results found that analysis by flow cytometry of both CD38 and ZAP-70 could be used in the evaluation of patients with CLL as strong prognosis markers. The complex immunophenotype in CLL could be used to define 2 main prognosis patterns: (1) cyclin D1—positive, CD38 positive, CD20 high, FMC7 positive, CD23 weak with poor prognosis; and (2) cyclin D1—negative, CD38 negative, CD20 low, FMC7 negative, CD23 high with good prognosis. These patterns have strong association with expression of ZAP-70 and could be used as prognosis assessment of patients with CLL.     

MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

B-Cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL/SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV_H), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival tunes than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P=0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV_H status were independent unfavorable prognostic factors in patients with B-CLL/SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL/SLL. The biological role and mechanism of action of MUM1 in B-CLL/SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.