Prognostic Factor In Malignant Mesothelioma Research Articles

Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis.

Background:Lactate dehydrogenase (LDH) as a hypoxia-regulator plays a vital role in alternative metabolic pathways of cancer cells. Numerous studies have assessed the prognostic value of elevated pretreatment LDH in malignant mesothelioma (MM). However, the results have been largely inconsistent. Hence, the aim of current study was to investigate the prognostic value of pretreatment LDH levels in patients with MM by performing a meta-analysis of relevant studies.Methods:A literature search for English language studies, which investigated the association of LDH levels with overall survival (OS) in malignant mesothelioma, was performed in the electronic databases, PubMed, Medline, Embase, and Web of Science. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated. Heterogeneity was assessed using Cochran Q and I2 statistics. Sensitivity analysis, meta-regression model, and subgroup analysis were performed to trace the source of heterogeneity, if applicable.Results:A total of 9 studies with a combined study population of 1977 patients came within the purview of this meta analysis. Pooled HR for OS in patients with high LDH level was 1.68 (95% CI = 1.36–2.00). Significant heterogeneity was observed in the included studies (I2 = 54.1%, P = 0.026). Sensitivity analysis after sequential exclusion of 1 study at a time, and meta-regression with inclusion of 6 confounding factors failed to identify the source of heterogeneity. However, in the subgroup analysis, it was found that the publication of Nojiri et al was the origin of heterogeneity. When omitted the publication of Nojiri et al, the pooled HR of the rest 8 studies was 1.83 (95% CI = 1.45–2.20, I2 = 0.0%, P = 0.723). Egger test and funnel plots excluded the possibility of publication bias affecting the results of the current meta-analysis.Conclusion:A negative association was observed between high LDH levels and poor overall survival in the current study. Our findings suggest that pretreatment LDH level could serve as a useful predictor of prognosis in patients with malignant mesothelioma.

Pretreatment thrombocytosis as a significant prognostic factor in malignant mesothelioma: a meta-analysis

The current meta-analysis analyzed the prognostic impact of elevated platelet count before the treatment of malignant mesothelioma (MM). We performed a search for articles published up to April 15, 2016 in PubMed, MEDLINE, EMBASE, and Web of Science, which evaluated elevated platelet count and survival outcome of MM. STATA version 12 was used for statistical analysis. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were combined to calculate overall effects. The assessment of heterogeneity was tested by the Cochran Q and I2 statistics. The sensitivity and meta-regression analyses were performed to explore the origin of heterogeneity. We analyzed 18 eligible studies (3602 patients) that evaluated the correlation between pretreatment platelet count and overall survival (OS). Elevated platelet count was a prognostic factor of poor OS, with a pooled HR of 1.56 (95% CI = 1.36–1.77). However, significant heterogeneity was observed in the included studies (I2 = 86.0%, p < 0.001). Sensitivity and meta-regression analyses were performed to trace the origin of heterogeneity. Only the variable type (multivariable or univariate model) was traced as the origin of heterogeneity. Hence, we conducted a subgroup analysis of variable type. The HR was 1.66 (95% CI = 1.41–1.91) in the multivariable group and no significant heterogeneity was observed (I2 = 0.0%, p = 0.476). In conclusion, high pretreatment platelet count resulted in poor OS in MM. Therefore, platelet count could be an adequate and useful factor of prognosis for MM.

Comparative genetics of diffuse malignant mesothelioma tumors of the peritoneumand pleura, with focus on BAP1 expression.

Malignant mesothelioma (MM) is a malignancy arising from the mesothelial cells lining the thoracic and abdominal serosal cavities. The pleural space is the most commonly affected site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. The different types of mesotheliomas are generally considered as distinct diseases with specific risk factors, therapeutic strategies and prognoses. Epidemiological and clinical differences between pleural and peritoneal MM raise questions about the involvement of different molecular mechanisms. Since the BAP1 gene is involved in the BAP1 cancer syndrome and seems to be a prognostic factor in MM, this review presents an overview of BAP1 alterations in mesothelioma comparing pleural and peritoneal localizations.

Yes is a central mediator of cell growth in malignant mesothelioma cells

The constitutive activation of the Src family kinases (SFKs) has been established as a poor prognostic factor in malignant mesothelioma (MM), however, the family member(s) which contribute to the malignancy have not been defined. This study aimed to identify the SFK member(s) contributing to cell growth using RNA interference in various MM cell lines. Silencing of Yes but not of c-Src or Fyn in MM cells leads to cell growth suppression. This suppressive effect caused by Yes silencing mainly depends on G1 cell cycle arrest and partly the induction of apoptosis. Also, the knockout of Yes induces the inactivation of β-catenin signaling and subsequently decreases the levels of cyclin D necessary for G1-S transition in the cell cycle. In addition, Yes knockout has less effect on cell growth suppression in β-catenin-deficient H28 MM cells compared to other MM cells which express the catenin. Overall, we conclude that Yes is a central mediator for MM cell growth that is not shared with other SFKs such as c-Src.

New pyrazolo[3,4-d]pyrimidine SRC inhibitors induce apoptosis in mesothelioma cell lines through p27 nuclear stabilization

Malignant mesothelioma (MM) is a highly aggressive tumor of the serous membranes for which there is currently no effective curative modality. Recent data suggest that hyperactivation of the tyrosine kinase SRC has a key role in MM development and therefore this kinase represents an important molecular target for MM therapy. We tested new pyrazolo[3,4-d]pyrimidine SRC inhibitors on a panel of MM cell lines expressing the active form of SRC. These SRC inhibitors exerted a significant proapoptotic effect on MM cells without affecting the normal mesothelial cell line MET-5A, supporting a possible use of these SRC inhibitors for a safe treatment of MM. We also showed that SRC inhibitor-induced apoptosis occurred concomitantly with an increase in the nuclear stability of the cyclin-dependent kinase inhibitor p27. This finding is remarkable considering that loss of nuclear p27 expression is a well-established adverse prognostic factor in MM, and p27 nuclear localization is crucial for its tumor-suppressive function. Consistently, SRC inhibition seems to promote the increase in p27 nuclear level also by inactivating the AKT kinase and downregulating cyclin D1, which would otherwise delay p27 nuclear import and provoke its cytoplasmic accumulation. To determine whether p27 stabilization has a direct role in apoptosis induced by SRC inhibition, we stably silenced the CDKN1B gene, encoding p27, in MSTO-211H and REN mesothelioma cells by transduction with lentiviral vectors expressing short hairpin RNAs against the CDKN1B transcript. Strikingly, p27 silencing was able to suppress the apoptosis induced by these SRC inhibitors in both MM cell lines, suggesting that p27 has a crucial proapoptotic role in MM cells treated with SRC inhibitors. Our findings reveal a new mechanism, dependent on p27 nuclear stabilization, by which SRC inhibition can induce apoptosis in MM cells and provide a new rationale for the use of SRC inhibitors in MM therapy.

Mesothelin-related predictive and prognostic factors in malignant mesothelioma: A nested case–control study

Soluble mesothelin-related protein (SMRP) in serum is potentially a sensitive marker of malignant mesothelioma (MM) diagnosis and progression, and may be useful as screening marker. Mesothelin expression in tumors is regarded as a sensitive marker for diagnosis and disease progression, and is a candidate prognostic marker. Levels of SMRP, CA125 and CYFRA 21-1 in pre-diagnostic (1-30 years) serum samples from 47 mesothelioma cases and 141 matched controls were analysed. Mesothelin expression in tumors was assessed. The association between biomarker level and mesothelioma risk and survival was analysed, adjusting for asbestos exposure. Survival related to tumor mesothelin expression, age, sex, histological type, location, asbestos exposure and pre-clinical SMRP was analysed. There was no significant association between biomarker levels and mesothelioma risk when analysed as continuous variables or as tertiles. Biomarker levels <10, 10-19 and >or=20 years before diagnosis were not significantly associated to mesothelioma risk. Mesothelin expressed in >50% of tumor cells was seen in 36 of 47 (77%) tumors. Mesothelin expression in <50% of tumor cells was a significant negative prognostic marker in all cases of malignant mesothelioma (median survival=6 months vs. 12 months, hazard ratio (HR)=2.49, 95%CI 1.17-5.27), and also when only epithelial mesothelioma was analysed (median=6 months vs. 14 months, HR=2.36, 95%CI 1.07-5.22). When adjusted for age and gender, the prognosis was still dismal, but non-significant (HR=1.85, 95%CI 0.85-4.05). High age (>65 years) was an independent negative prognostic factor that was related to both mesothelin expression and asbestos exposure. Mesothelioma of the epithelial type of the peritoneum had a significantly longer survival than epithelial type in pleura and was also related to mesothelin expression.

Cytogenetic and molecular genetic changes in malignant mesothelioma

Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events, especially deletions, which lead to the inactivation of multiple onco-suppressor genes in a multistep cascade mechanism. Past asbestos exposure represents the major risk factor for MM, and the link between asbestos fibers and MM has been largely proved by several epidemiologic and experimental studies. Asbestos fibers induce DNA and chromosomal damage. Most MM cases have shown multiple chromosomal abnormalities. Chromosomal losses are more common than gains. The most common cytogenetic abnormality in MM is a deletion in 9p21, the locus of CDKN2A, a tumor suppressor gene (TSG). The deletion of CDKN2A is a negative prognostic factor in MM. Loss of TSG CDKN2A/ p14 ARF is also common in MM and mutations in NF2 occur in approximately half of the cases. Despite the ban on asbestos use in Western countries, the incidence of MM is increasing, and asbestos is still used in developing countries. This epidemiologic situation calls for further research. Ongoing studies are already applying high-throughput genomic profiling methods in MM. Genetic alterations observed in MM may be useful in differential diagnosis between lung cancer and MM, as diagnostic markers or therapeutic targets, and as indicators of premalignancy for primary prevention and health surveillance.

&lt;![CDATA[&lt;B&gt;Morphological aspects as prognostic factors in malignant mesothelioma&lt;/B&gt;: &lt;B&gt;a study of 58 cases&lt;/B&gt;]]&gt;

&lt;![CDATA[&lt;B&gt;Morphological aspects as prognostic factors in malignant mesothelioma&lt;/B&gt;: &lt;B&gt;a study of 58 cases&lt;/B&gt;]]&gt;

Prognostic Significance of Vascular Endothelial Growth Factor, Tumor Necrosis, and Mitotic Activity Index in Malignant Pleural Mesothelioma

Tumor growth and metastasis are angiogenesis-dependent events, and several prognostic factors have been determined in malignant mesothelioma. In this study, we investigated the prognostic significance of vascular endothelial growth factor (VEGF), tumor necrosis (TN), and mitotic activity index (MAI) in malignant mesothelioma. For the first time (to our knowledge), we also demonstrated the association between VEGF staining, TN, and MAI in malignant mesothelioma. Decortication and VATS materials of 40 patients were investigated. The routinely processed formalin-fixed, paraffin-embedded, hematoxylin-eosin-stained tumor sections that had been used for the original diagnostic purposes were retrieved. Hematoxylin-eosin sections were selected for VEGF immunostaining, TN, and mitotic count. Clinicopathologic data, stage of disease, and survival of patients were all determined. The correlations between variables were evaluated by Spearman rank correlation test. Both univariate analysis using the log-rank test and multivariate analysis using Cox regression model were performed for survival analysis. There was a significant correlation between VEGF staining and TN (r = 0.42, p = 0.006). In univariate analysis, both VEGF staining (p = 0.0002) and TN (p = 0.0055) showed significant correlation with short survival. Also, there was a positive correlation between VEGF and tumor stage (p = 0.046). In multivariate analysis, only VEGF was determined as an independent prognostic factor in malignant mesothelioma (p = 0.001). There was no association between MAI and survival (p = 0.504). VEGF, known as an important angiogenic peptide, is an independent prognostic factor in malignant pleural mesothelioma. TN stimulates angiogenesis, and we observed a significant correlation between VEGF and TN. However, further studies are needed to evaluate the prognostic significance of angiogenic properties in malignant mesothelioma.

Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma

In the UK mortality from malignant mesothelioma (MM) is likely to more than double over the next 20 years and despite advances in surgery, chemotherapy and radiation treatment the overall prognosis for patients remains poor. A number of scoring systems based on assessment of clinicopathological features of patients with the disease have been developed but the search continues for further prognostic indicators. Angiogenesis, tumour necrosis (TN), epidermal growth factor receptor (EGFR) expression, cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) have been linked with poor prognosis in some types of solid tumour and their relevance as prognostic factors in malignant mesothelioma is examined in this paper.

Tumor Necrosis Correlates With Angiogenesis and Is a Predictor of Poor Prognosis in Malignant Mesothelioma

Malignant mesothelioma (MM) is a fatal tumor of increasing incidence related to asbestos exposure. Microscopic tumor necrosis (TN) is a poor prognostic factor in solid tumors, but it has not been characterized in MM. We wished to evaluate the incidence of TN in MM and its correlations with clinicopathologic factors, angiogenesis, and survival. TN was graded in 171 routine formalin-fixed, paraffin-embedded hematoxylin-eosin-stained tumor sections by two independent observers. Angiogenesis was assessed by the microvessel count (MVC) of CD34 immunostained sections. TN was correlated with survival by Kaplan-Meier and log-rank analysis, and stepwise, multivariate Cox models were used to compare TN with angiogenesis and established prognostic factors and prognostic scoring systems. TN was identified in 39 cases (22.8%) and correlated with low hemoglobin (p = 0.01), thrombocytosis (p = 0.04), and high MVC (p = 0.02). TN was a poor prognostic factor in univariate analysis (p = 0.008). Patients with TN had a median survival of 5.3 months vs 8.3 months in negative cases. Independent indicators of poor prognosis in multivariate analysis were nonepithelioid cell type (p = 0.0001), performance status > 0 (p = 0.007), and increasing MVC (p = 0.004) but not TN. TN contributed independently to the European Organisation for Research and Treatment of Cancer (EORTC) [p = 0.03] and to the Cancer and Leukemia Group B (CALGB) [p = 0.03] prognostic groups in respective multivariate Cox analyses. TN correlates with angiogenesis and is a poor prognostic factor in MM. TN contributes to the EORTC and CALGB prognostic scoring systems.

Prognostic factors in mesothelioma

Prognostic factors in oncology may help physicians give their patients a prognosis for their disease and thus allow them to make plans for the future. These factors also assist in the selection of patients more likely to benefit from intensive treatments, especially in the context of clinical trials. Recently it has become clear that prognostic factors may have an additional benefit: they may provide insight into the biology of the cancer being studied and lead to improved understanding of the molecular pathogenesis. For malignant mesthelioma, the prognostic scoring systems of the Cancer and Leukemia Group B (CALGB) and European Organization for Research and Treatment of Cancer (EORTC) are the most useful of those currently available. These systems rate performance status, age, histological subtype, weight loss, and hematological parameters as the best prognostic factors for malignant mesothelioma. In the future, biological markers may provide additional information on mesothelioma and will help in prognostication. Semin Oncol 29:36-40. Copyright © 2002 by W.B. Saunders Company.

Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems

BACKGROUNDThe incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in...

High microvessel density is an independent poor prognostic factor in malignant mesothelioma

High microvessel density is an independent poor prognostic factor in malignant mesothelioma

Prognostic factors in malignant mesothelioma: where do we go from here?

Prognostic factors in malignant mesothelioma: where do we go from here?

Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma.

Cytogenetic findings of our 30 previously reported and eight new patients with malignant pleural mesothelioma were summarised and correlated with asbestos fibre burden in lung tissue and survival. Successful cytogenetic analyses were performed on cells obtained from the tumours and/or pleural effusions of 34 of the 38 patients. Clonal chromosomal abnormalities were detected in 25 patients, 19 of them studied before treatment. Nine patients, seven of them studied before treatment, had normal karyotypes and/or non-clonal chromosomal abnormalities. Most of the karyotypic findings in the patients with clonal abnormalities were complex and heterogeneous, and no chromosome aberration specific to mesothelioma could be demonstrated. The following numerical abnormalities in decreasing order of frequency were preferentially present in karyotypic changes: -22, +7, -1, -3, -9, +11 and -14 (-/+ denoting partial or total loss or gain). Translocations and deletions involving a breakpoint at 1p11-p22 were the most frequent structural aberrations. Statistically significant correlations were found between high content of asbestos fibres in lung tissue and partial or total losses of chromosomes 1 and 4, and a breakpoint at 1p11-p22 (P = 0.0001, P = 0.003, P = 0.009, respectively). The number of copies of chromosome 7 short arms was inversely correlated with survival (P = 0.02). In this study no diagnostic cytogenetic markers of mesothelioma were found, instead the copy number of chromosome 7 short arms turned out to be a possible prognostic factor in malignant mesothelioma.