***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The 5-year survival rate of non-small cell lung carcinoma ( NSCLC ) has only marginally improved during the past two decades , despite advances in surgery and chemoradiotherapy . Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information , thus improving new therapeutic protocol s. We analyzed the predictive relevance of the  microvessel count ( MC ) , bcl-2 and p53 proteins , proliferative activity , and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC . The expression of biological parameters ( p53 , bcl-2 , proliferative activity , and MC ) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse . In the univariate analysis , the histotype , tumor status , node status , p53 , bcl-2 , and MC have been shown to significantly affect progression and death . In the multiple logistic regression analysis , the MC ( P < 0.000001 ) , tumor status ( P < 0.005 ) , and node status ( P < 0.0002 ) influenced the overall survival while prediction of relapse was strongly revealed by tumor status ( P < 0.005 ) , nodal metastatic involvement ( P < 0.000001 ) , and the assessment of the vascular count ( P < 0.0004 ) . These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future r and omized clinical trials BACKGROUND Findings from the phase 3 First-Line ErbituX in lung cancer ( FLEX ) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone ( hazard ratio [ HR ] 0·871 , 95 % CI 0·762 - 0·996 ; p=0·044 ) in patients with advanced non-small-cell lung cancer ( NSCLC ) . To define patients benefiting most from cetuximab , we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients . METHODS We used prospect ively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0 - 300 . We used response data to select an outcome -based discriminatory threshold immunohistochemistry score for EGFR expression of 200 . Treatment outcome was analysed in patients with low ( immunohistochemistry score < 200 ) and high ( ≥200 ) tumour EGFR expression . The primary endpoint in the FLEX study was overall survival . We analysed patients from the FLEX intention-to-treat ( ITT ) population . The FLEX study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS Tumour EGFR immunohistochemistry data were available for 1121 of 1125 ( 99·6 % ) patients from the FLEX study ITT population . High EGFR expression was scored for 345 ( 31 % ) evaluable patients and low for 776 ( 69 % ) patients . For patients in the high EGFR expression group , overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group ( median 12·0 months [ 95 % CI 10·2 - 15·2 ] vs 9·6 months [ 7·6 - 10·6 ] ; HR 0·73 , 0·58 - 0·93 ; p=0·011 ) , with no meaningful increase in side-effects . We recorded no corresponding survival benefit for patients in the low EGFR expression group ( median 9·8 months [ 8·9 - 12·2 ] vs 10·3 months [ 9·2 - 11·5 ] ; HR 0·99 , 0·84 - 1·16 ; p=0·88 ) . A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression ( p=0·044 ) . INTERPRETATION High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC . Assessment of EGFR expression could offer a personalised treatment approach in this setting . FUNDING Merck PURPOSE Approximately 30 % of patients with stage IB non-small-cell lung cancer ( NSCLC ) die within 5 years after surgery . Current staging methods are inadequate for predicting the prognosis of this particular subgroup . This study identifies prognostic markers for NSCLC . PATIENTS AND METHODS We used computer-generated r and om numbers to study 148 paraffin-embedded specimens for immunohistochemical analysis . We studied gene expression in paraffin-embedded specimens of lung cancer tissue from 73 r and omly selected patients with stage IB NSCLC who had undergone radical surgical resection and evaluated the association between the level of expression and survival . We used support vector machines (SVM)-based methods to develop three immunomarker-SVM-based prognostic classifiers for stage IB NSCLC . For validation , we used r and omly assigned specimens from 75 other patients . RESULTS We devised three immunomarker-SVM-based prognostic classifiers , including SVM1 , SVM2 , and SVM3 , to refine prognosis of stage IB NSCLC successfully . The SVM1 model integrates age , cancer cell type , and five markers , including CD34MVD , EMA , p21ras , p21WAF1 , and tissue inhibitors of metalloproteinases ( TIMP ) -2 . The SVM2 model integrates age , cancer cell type , and 19 markers , including BCL2 , caspase-9 , CD34MVD , low-molecular-weight cytokeratin , high-molecular-weight cytokeratin , cyclo-oxygenase-2 , EMA , HER2 , matrix metalloproteinases ( MMP ) -2 , MMP-9 , p16 , p21ras , p21WAF1 , p27kip1 , p53 , TIMP-1 , TIMP-2 , vascular endothelial growth factor ( VEGF ) , and beta-catenin . The SVM3 model consists of SVM1 and SVM2 . The three models were independent predictors of overall survival . We vali date d the classifiers with data from an independent cohort of 75 patients with stage IB NSCLC . CONCLUSION The three immunomarker-SVM-based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC Introduction : Cancer and Leukemia Group B 9633 was a phase III trial that r and omized patients with stage IB non-small cell lung cancer to observation or four cycles of carboplatin and paclitaxel . A statistically significant effect in favor of adjuvant chemotherapy was seen for disease-free survival ( DFS ) and overall survival ( OS ) in the subgroup of patients with tumors ≥4 cm . A laboratory companion study was conducted to see whether molecular and clinical factors could provide additional prognostic information . Methods : Formalin-fixed , paraffin-embedded blocks were obtained for 250 of the 344 patients enrolled . Immunohistochemical staining for bcl-2 , p53 , blood group antigen A , and mucin was correlated with DFS and OS . Results : The prevalence of the markers was bcl-2 , 17 % ; p53 , 47 % ; blood group antigen A , 25 % ; and mucin , 45 % . Univariate analysis for DFS showed a statistically significant effect for the presence of mucin ( p = 0.0005 ) and p53 ( p = 0.05 ) and for OS showed a significant effect for mucin ( p = 0.0005 ) . In the multivariate Cox model , there was a statistically significant association between shorter DFS and presence of mucin ( p = 0.002 ; hazard ratio [ HR ] 2.05 ) and p53 ( p = 0.003 ; HR 1.95 ) and between shorter OS and presence of mucin ( p = 0.004 ; HR 2.03 ) and p53 ( p = 0.0005 ; HR 2.30 ) . Of the clinical factors , male gender and larger tumor volume were also significant adverse prognostic factors ( p < 0.05 ) . Conclusions : A statistically significant association between shorter DFS and OS was seen for the patients with p53 protein expression , mucin expression , male gender , and larger tumors in this cohort of patients with stage IB non-small cell lung cancer treated on Cancer and Leukemia Group B 9633 In patients with non-small cell lung cancer ( NSCLC ) , tumor expression of P21-Ras , HER2 , P53 , and Bcl-2 has been reported as independent predictors of prognosis . However , the prognostic information carried by these proteins has usually been determined separately , and their potential interaction has not been taken into account . We conducted immunostaining for P21-Ras , HER2 , P53 and Bcl-2  on 238 cases of NSCLC in a Korean population with 203 squamous cell carcinomas , and 35 adenocarcinomas .  P21-Ras , HER2 , P53 or Bcl-2 was expressed at high levels in 54.6 , 42.0 , 18.1 and 71.8 % of the NSCLC studied , respectively . A total of 59 tumors ( 24.8 % ) expressed only one protein , while 70 ( 29.4 % ) expressed two , 59 ( 24.8 ) expressed three , and 17 tumors ( 7.1 % ) expressed all four proteins . Univariate analysis testing the association of marker expression with survival found Bcl-2 expression to be significantly associated with a poor prognosis , as well as the co-expression of Bcl-2 + HER2 , Bcl-2 + HER2 + P53 , and Bcl-2 + HER2 + P53 + P21-ras with an increasing hazard ratio . By multivariate analysis controlling for age , tumor stage and tumor type , only the combination of Bcl-2 + HER2 expression was an independent marker of poor prognosis ( hazard ratio = 1.91 , P = 0.003 ) . Thus , a prospect i ve analysis of the co-expression of Bcl-2 + HER2 in NSCLC patients may identify patients with a poor prognosis who may benefit from more aggressive therapy BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline .  Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Objective : We used a large patient population to identify immunohistochemical biomarkers to enable improved prognostication in patients with non-small cell lung carcinoma ( NSCLC ) . Methods : A tissue microarray was constructed using duplicate 0.6 mm cores of formalin-fixed paraffin-embedded tissue blocks from 609 patients with NSCLC .  Immunohistochemical was used to detect 11 biomarkers including epidermal growth factor receptor , Her2 , Her3 , p53 , p63 , bcl-1 , bcl-2 , Thyroid transcription factor , carcinoembryonic antigen , chromogranin , and synaptophysin . A clinical data base was generated prospect ively at the time of tissue collection . Survival outcomes were obtained from a Provincial Cancer Registry data base . Univariate and multivariate analyses were performed to look for a relationship between biomarker expression , smoking history , and survival . Results : Survival 
    Output:
    
Our present meta- analysis demonstrated favorable prognostic values of Bcl-2 expression in patients with NSCLC .