Kaija Vasala

Matrix metalloproteinase-2 immunoreactive protein as a prognostic marker inbladder cancer

Abstract Objectives To analyze the expression of matrix metalloproteinase-2 (MMP-2) in bladder cancer specimens and evaluate its value as a prognostic biomarker. MMPs, particularly MMP-2, play an important role in tumor cell invasion and metastasis in several human cancers. Methods The MMP-2 protein was assayed semiquantitatively in 54 primary bladder carcinomas of varying grade and stage. A specific monoclonal antibody for MMP-2 was used to detect the antigen by a semiquantitative immunohistochemical staining of paraffin-embedded tissue sections. Results Of the 54 specimens, 35 (65%) overexpressed MMP-2 protein when stained sections were scored independently by three observers. A consensus score was established before clinical data analysis. The 5-year disease-specific survival was significantly ( P = 0.0335) lower in the MMP-2 positive cases (n = 35) than in the MMP-2 negative cases (n = 19), 53% versus 77%. The 5 and 10-year relapse-free survival rate was 32% and 24% in the MMP-2 positive patients, respectively, compared with 68% for the MMP-2 negative patients ( P = 0.0718). MMP-2 overexpression correlated with bladder cancer stage but not with grade, partly contrary to previous observations. Conclusions The results of this study demonstrated that MMP-2 protein overexpression may be an independent prognostic biomarker for bladder cancer progression.

Engraftment and outcome after autologous stem cell transplantation in plerixafor-mobilized non-Hodgkin's lymphoma patients

Plerixafor is used in combination with granulocyte–colony‐stimulating factor to enhance the mobilization of hematopoietic stem cells. Limited data are available in regard to effects of plerixafor on posttransplant outcomes in chemomobilized patients who appear to mobilize poorly.

Blood graft cellular composition and posttransplant recovery in non-Hodgkin's lymphoma patients mobilized with or without plerixafor: a prospective comparison

Autologous stem cell transplantation is commonly used to treat non‐Hodgkins lymphomas (NHLs). Cellular composition of the blood grafts apparently has a role in the posttransplant hematologic and immune recovery. Plerixafor increases the mobilization of CD34+ cells and higher amounts of various lymphocyte subsets have been reported in the grafts. Limited prospective data are available in regard to graft cellular composition, hematologic and immune recovery, and patient outcomes in NHL patients who receive plerixafor added to chemomobilization.

Low circulating levels of ProMMP-2 are associated with adverse prognosis in bladder cancer.

Objectives: In this study the serum levels of proMMP-2, active MMP-2, TIMP-2 and MMP-2:TIMP2 complex were evaluated. We also studied the correlation of these parameters with clinicopathological parameters in patients suffering from bladder carcinoma and outcome in this patient group. Methods: The levels of circulating proMMP-2, active MMP-2, proMMP-9, TIMP-1, TIMP-2 and MMP-2:TIMP-2 complex of 84 patients with bladder cancer were measured by ELISA. The proMMP-2 and TIMP-2 immunoreactive proteins were studied. These results were compared to clinicopathological parameters and patient outcome. Results: Low circulating proMMP-2 levels significantly correlated with poor prognosis. The 5-year disease-specific survival rate was 46% in patients with high levels of proMMP-2 versus 23% in patients with low proMMP-2 levels (p = 0.011). Low TIMP-2 levels could also present as a marker of poor prognosis. In this study, the 5-year disease-specific survival in patients with low circulating TIMP-2 levels was 19% compared to 66% in patients with high TIMP-2 levels (p = 0.004). Conclusion: These results indicate that high levels of circulating proMMP-2 and TIMP-2 levels are both associated with a better clinical course; moreover, total proMMP-2 is an independent prognostic marker of bladder cancer progression.

Early immune recovery after autologous transplantation in non-Hodgkin lymphoma patients: predictive factors and clinical significance

Abstract Limited data is available about the factors affecting early immune recovery or its clinical significance after autologous stem cell transplantation (auto-SCT). We prospectively analyzed factors affecting early immune recovery and outcome among 72 non-Hodgkin lymphoma (NHL) patients. Absolute lymphocyte count 15 d after auto-SCT (ALC-15) ≥ 0.5 × 109/L was associated with the use of plerixafor (p = 0.004), the number of CD34+ cells (p = 0.015), and CD34+ CD38− cells (p = 0.005) in the grafts. ALC-15 ≥ 0.5 × 109/L was associated with improved overall survival (p = 0.021). In patients with aggressive histology, ALC-15 ≥ 0.5 × 109/L was beneficial in regard to both progression-free survival (p = 0.015) and overall survival (p = 0.002). Early immune recovery seems to be important in transplanted patients with NHL and, therefore, an easy and affordable method for disease-related risk analysis. Patients with aggressive histology and slow immune recovery may need additional post-transplant treatment.

Constant pattern of relapse in primary central nervous lymphoma patients treated with high-dose methotrexate combinations. A Finnish retrospective study

Abstract Background. Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome is poor. Material and methods. We performed a hospital-based retrospective analysis to evaluate the long-term results of the Nordic type of Bonn chemotherapy regimen in PCNSL patients. The study included 54 patients with newly diagnosed PCNSL who received chemotherapy with curative intent as their first-line treatment. Results. We found promising response rates, 76% of the patients achieving CR and 22% patients achieving PR, with corresponding two-year EFS 53% and OS 76%. However, with longer follow-up a constant pattern of relapses was observed with only one patient remaining in primary remission after 60 months. Discussion. The finding suggests that basic biological differences exist between PCNSL and systemic diffuse large B-cell lymphoma and there is a need for consolidation or maintenance therapy after achieving a remission in patients with PCNSL.

Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma

Summary In this work, we have studied the biology behind DLBCL central nervous system (CNS) tropism and potential biomarkers for CNS relapse prediction. We show that ITGA10, PTEN, CD44, cadherin-11 and lactoferrin levels are altered in CNS lymphomas.

Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent immunohistochemical (IHC) high expression of MYC and BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155 patients uniformly treated with R-CHOP-like therapies. We performed direct sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6. In multivariate analysis, TP53 mutations in L3 and loop-sheet helix (LSH) associated with a risk ratio (RR) of disease-specific survival (DSS) of 8.779 (p = 0.022) and a RR of disease-free survival (DFS) of 10.498 (p = 0.011). In IHC analysis BCL-2 overexpression was associated with inferior DFS (p = 0.002) and DSS (p = 0.002). DLBCL with BCL-2 and MYC overexpression conferred inferior survival in all patients (DSS, p = 0.038 and DFS, p = 0.011) and in patients with non-GC phenotype (DSS (p = 0.013) and DFS (p = 0.010). Our results imply that in DLBCL, the location of TP53 mutations and IHC analysis of BCL-2 and MYC might have a role in the assessment of prognosis.