Expression of nm23-H1 is associated with poor prognosis in peripheral T-cell lymphoma

We have reported previously that the serum nm23-H1 level is a prognostic factor for non-Hodgkin's lymphoma. In this study, we examined nm23-H1 expression in T- and natural killer (NK)-cell lymphoma in order to evaluate whether lymphoma cells produce the protein. The clinical significance of the cytotoxic molecules, T-cell intracellular antigen-1 (TIA-1) and granzyme B and nm23-H1 expression were also examined. Expression of nm23-H1, TIA-1, or granzyme B was examined by immunohistochemistry in 137 previously untreated lymphoma patients. The relationship between the results and clinical outcome was examined in 81 patients with angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, or peripheral T-cell lymphoma, unspecified. The neoplastic cells of some lymphomas produced nm23-H1 and the expression rates of nm-23-H1, TIA-1 and granzyme B were 36.5%, 78.8% and 32.8% respectively. The nm23-H1-positive or TIA-1-positive groups had significantly shorter overall and disease-free survivals. Multivariate analysis confirmed nm23-H1 expression to be an independent prognostic factor. The nm23-H1 protein can be an important prognostic factor in the lymphomas studied here. New treatments that target nm23 overexpression could be developed as a result of nm23-HI production by lymphoma cells.     

Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia

Leukemic cells from 31 (7.6%) of 409 children with newly diagnosed acute lymphoblastic leukemia (ALL) had a hypodiploid karyotype. The patients' ages ranged from 0.8 to 17 years (median, 5 years) and their initial leukocyte counts from 1.0 to 132 X 10(9)/L (median, 12.7 X 10(9)/L). Modal chromosome numbers for the leukemic stem lines were 45 in 26 cases, 28 in two cases, and 26, 36 and 43 in one case each. Seven cases had one to three additional abnormal lines due to clonal evolution. Chromosome 20 was lost most frequently (nine cases). Structural abnormalities--including chromosomal translocations (21 cases), deletions (ten cases), duplications (two cases), or inversions (one case)--were common findings; the nonrandom translocations consisted of the t(1;19)(q23;p13.3) in two pre-B cases and tdic(9;12)(p1?1;p1?2) in three cases of common ALL. When compared with hyperdiploid cases (greater than 50 chromosomes), ALL with hypodiploidy was found to have a poorer outcome and was more likely to be associated with chromosomal translocations, higher serum lactic dehydrogenase levels, and age less than 2 or greater than or equal to 10 years. Moreover, patients with hypodiploid ALL fared as poorly as those with pseudodiploid karyotypes, even though their leukocyte counts and serum lactic dehydrogenase levels were lower and they had a comparable frequency of leukemic cell translocations. Hypodiploidy is therefore an unfavorable karyotypic feature in childhood ALL.     

High expression of GSKIP is associated with poor prognosis in meningioma

Meningiomas are the most common extra-axial primary central nervous system tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. glycogen synthesis kinase 3β interaction protein (GSKIP) is an A-kinase anchor protein that has cytosolic scaffolding function and binds to a protein kinase A and glycogen synthesis kinase 3β to modulate different biological processes and malignant tumorigenesis through the Wnt pathway. The purpose of this study was to investigate the relationship between GSKIP expression and the clinico-pathological parameters in meningioma using immunohistochemical staining. We collected samples from 74 patients, from 2008 to 2012, in the Kaohsiung Medical University Hospital that had data on the staging and prognosis of the meningioma pathological section. Chi-square, Kaplan-Meier method, and cox regression were used to analyze the correlation between clinical parameters and immunohistochemistry staining for GSKIP. Following our immunohistochemical score, we found that higher expression of GSKIP was associated with high World Health Organization grading, recurrence, malignant transformation, and reduced overall survival time and recurrence-free survival time in meningioma. GSKIP may be a biomarker of poor prognosis and a target protein for therapy in meningioma.     

p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.     

Peripheral blood involvement in patients with follicular lymphoma: a rare disease manifestation associated with poor prognosis

Follicular Lymphoma (FL) is the second most common non‐Hodgkin lymphoma (NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase (FL‐LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon‐Sud hospital, 37 (7·4%) had characteristic FL‐LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL‐LP at study entry. In order to evaluate the outcome of this Lyon‐Sud cohort, FL‐LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index (FLIPI) score, age and treatment. Presence of FL‐LP was associated with shorter progression‐free survival (PFS) and overall survival (OS) (P = 0·004 and P = 0·031, respectively). Presence of FL‐LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression (TTP). A number of circulating lymphoma cells (CLC) >4 × 10⁹/l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL‐LP on TTP was validated in the PRIMA cohort (P = 0·0004). In conclusion, FL‐LP is a rare event associated with shorter PFS and patients with CLC >4 × 10⁹/l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options.     

MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis

Chromosomal translocations that involve MYC , characteristic of Burkitt lymphoma, are rare in chronic lymphocytic leukaemia (CLL). We report the clinical, morphological, immunophenotypic, cytogenetic and molecular genetic features of eight CLL cases with MYC rearrangement. The patients, five men and three women (median age, 71 years) had bone marrow involvement and an absolute peripheral blood lymphocytosis; five had lymphadenopathy; seven had splenomegaly. Prolymphocytes were increased (≥10%) in all cases. Six cases were classified as CLL with increased prolymphocytes (CLL/PL; prolymphocytes 10–55%), and two were classified as CLL in prolymphocytic transformation (CLL/PT; prolymphocytes >55%). All cases co-expressed CD5, CD19, and CD23; five of eight expressed ZAP-70. Of seven cases tested, four had mutated and three had unmutated IGHV genes. Conventional cytogenetic studies demonstrated t(8;14)(q24·1;q32) in five cases, t(8;22)(q24·1;q11) in two cases, and t(2;8)(p12;q24·1) in one case. Seven cases contained additional chromosomal abnormalities. All patients received combination chemotherapy. Two developed Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphomas (DLBCL) that were clonally unrelated to the CLL. At follow-up, two patients are alive, four died of underlying disease, one died of EBV-associated DLBCL, and one died of an unrelated cancer. In summary, MYC rearrangement, which occurs rarely in CLL patients, is associated with increased prolymphocytes, complex cytogenetic abnormalities, and a poor prognosis.     

Acidic urine is associated with poor prognosis in patients with chronic heart failure

Renal dysfunction is reported to be associated with poor outcomes in patients with chronic heart failure (CHF). A recent study showed that acidic urine is related to chronic kidney disease, which is a risk factor for the development of CHF. However, it remains to be determined whether acidic urine is associated with poor outcomes in patients with CHF. We measured urine pH using dipsticks in 537 patients with CHF. Acidic urine was defined as urine pH ≤5.5. Patients were prospectively followed during a median follow-up period of 556 days. There were 145 cardiac events. Prevalence of acidic urine was increased with advancing stage of chronic kidney disease. Patients with acidic urine had a more severe New York Heart Association functional class compared with those with normal urine. In the multivariate Cox proportional hazard analysis, acidic urine was independently associated with poor outcomes in patients with CHF after adjustment of confounding factors. A Kaplan–Meier analysis demonstrated that the rate of cardiac events was higher in patients with acidic urine than in those with normal urine. The presence of acidic urine can reliably identify patients at high risk of future cardiac events in patients with CHF.     

Persistent antiphospholipid antibodies are associated with thrombotic events in ANCA-associated vasculitis: A retrospective monocentric study

AimWe investigated whether persistent antiphospholipid syndrome (APLAs) at diagnosis are associated with the risk of thrombotic events during follow-up in patients with ANCA-associated vasculitis (AAV).MethodsWe retrospectively reviewed the medical records of 138 AAV patients. Thrombotic events were defined as arterial and venous thrombosis confirmed by magnetic resonance imaging, computed tomography, angiography and Doppler ultrasonography. Clinical and laboratory variables at diagnosis and during follow-up between patients with and without thrombotic events were compared. The univariable and multivariable Cox hazard model analyse to appropriately obtain hazard ratio (HR) considering the follow-up duration were conducted.ResultsThe mean age of 138 AAV patients was 55.1 years and 44 were male. Persistent APLAs were detected in 18 patients with AAV (13.0%). Thrombotic events were observed in 26 patients with AAV (18.8%) during follow-up. At the time of a retrospective study point, persistent APLAs at diagnosis were observed more frequently in patients with thrombotic events than those without. In the multivariable Cox hazard model analysis, age at diagnosis (HR 1.075) and persistent APLAs (HR 2.902), but not ANCAs. Thrombotic events were identified more frequently in patients with persistent APLAs at diagnosis than those without (38.9% vs. 15.8%, relative risk 3.383).ConclusionPersistent APLAs at diagnosis are significantly associated with the risk of thrombotic events during follow-up of AAV. We suggest that physicians should closely monitor the development of thrombotic events during follow-up.     

Over-expression of CXCL2 is associated with poor prognosis in patients with ovarian cancer

Background:In the present study, we aimed to detect the expression of CXCL2 in epithelial ovarian cancer (OC) and explore its clinical significance.Methods:TCGA (The Cancer Genome Atlas) database was adopted to assess the significance of CXCL2. Tissue microarray and immunohistochemical staining were used to detect the expression of CXCL2 in epithelial OC, and its correlation with clinicopathological features and prognosis was statistically analyzed.Results:CXCL2 was highly expressed in epithelial OC tissues compared with the adjacent tissues. Such up-regulation of CXCL2 was significantly correlated with tumor differentiation (P = .001), tumor stage (P = .01), tumor location (unilateral or bilateral) (P = .003), and metastasis (P = .003). Kaplan-Meier and Cox proportional hazards regression analyses showed that high expression of CXCL2 was not an independent predictor of poor prognosis in epithelial OC.Conclusions:Collectively, the high expression of CXCL2 might be related to the invasion and metastasis of epithelial OC.     

Nonmuscle myosin IIA is associated with poor prognosis of esophageal squamous cancer

Nonmuscle myosin IIA (myosin IIA) is a force-producing protein involved in the process of cell migration. Its expression has been considered as a bad prognostic indicator in stage I lung adenocarcinoma. However, the expression and clinical significance of myosin IIA in esophageal cancer has not been explored. In this study, we investigate the expression level of myosin IIA in 50 esophageal squamous cancer and 30 adjacent normal esophageal tissues by immunohistochemical staining and correlated its expression with clinicopathological features. Myosin IIA was expressed in all esophageal squamous cancer tissues (100%) and 8 of 30 adjacent normal tissues (26.7%, P = 0.000). In cancer tissues, elevated myosin IIA expression level was significantly correlated with increasing metastatic lymph nodes, poorer cancer differentiation, and advanced tumor stage. Further univariate analysis suggested that strong myosin IIA expression was associated with a significantly shorter overall survival (P = 0.021). In addition, MYH9 SiRNA was transfected into esophageal squamous cancer cell line (KYSE-510) to study the role of myosin IIA in cell migration. SiRNA-mediated depletion of myosin IIA in KYSE-510 cells significantly increased cell-matrix adhesion and attenuated cell migration ability (P = 0.000). In conclusion, these findings indicate that overexpression of myosin IIA may contribute to the progression and poor prognosis of esophageal squamous cancer, and this effect may be associated with increased cancer cell migration.