The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients

Kim, Young‐Chul; Park, Kyung‐Ok; Kern, Jeffrey A.; Park, Chang‐Soo; Lim, Sung‐Chul; Jang, An‐Soo; Yang, Jae-Beom

doi:10.1016/s0169-5002(98)00086-5

Cited by 79 publications

(48 citation statements)

References 19 publications

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“…A total of 29 trials, published between 1993 and 1999, were selected (Pezzella et al, 1993;Fontanini et al, 1995Fontanini et al, , 1996Walker et al, 1995;Brambilla et al, 1996;Kaiser et al, 1996;Ohsaki et al, 1996;O'Neill et al, 1996;Rao et al, 1996;Takayama et al, 1996;Anton et al, 1997;Apolinario et al, 1997;Higashiyama et al, 1997;Ishida et al, 1997;Koukourakis et al, 1997;Pastorino et al, 1997;Greatens et al, 1998;Kim et al, 1998;Kwiatkowski et al, 1998;Chen et al, 1999;D'Amico et al, 1999;Dingemans et al, 1999;Dosaka-Akita et al, 1999;Eerola et al, 1999;Ghosh et al, 1999;Huang et al, 1999;Laudanski et al, 1999;Maitra et al, 1999;Santinelli et al, 1999). They all report on the prognostic value for survival of Bcl-2 status in lung cancer patients, assessing Bcl-2 protein expression in the primary tumour.…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

“…Recent publications have attempted to correlate survival with factors related to angiogenesis (basic fibroblast growth factor, thrombospondin, vascular endothelial growth factor), to apoptosis (Bcl-2, p53), to control cell cycle (cyclins, MDM2, retinoblastoma gene), to growth (epithelial growth factor, erb-B2) and some other factors (serum lactate dehydrogenase (LDH), serum CYFRA21 level, white blood cell count and DNA aneuploidy content). The literature assessing their effects on survival (Strauss et al, 1995;Brambilla et al, 1996;Pujol, 1997;Kim et al, 1998;Kwiatkowski et al, 1998;The Bcl-2 gene was originally discovered in a follicular B-cell lymphoma, where a chromosomal translocation t(14:18) moves the Bcl-2 gene into juxtaposition with transcriptional enhancer elements of the immunoglobulin heavy chain locus. (Tsujimoto and Croce, 1986;Aisemberg et al, 1988).…”

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confidence: 99%

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Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

et al. 2003

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The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-2 in lung cancer and reported analysis of survival data according to Bcl-2 status. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a quality scale designed by the European Lung Cancer Working Party (including study design, laboratory methods and analysis). Of 28 studies, 11 identified Bcl-2 expression as a favourable prognostic factor and three linked it with poor prognosis; 14 trials were not significant. No differences in scoring measurement were detected between the studies, except that significantly higher scores were found in the trials with the largest sample sizes. Assessments of methodology and of laboratory technique were made independently of the conclusion of the trials. A total of 25 trials, comprising 3370 patients, provided sufficient information for the meta-analysis. The studies were categorised according to histology, disease stage and laboratory technique. The combined hazard ratio (HR) suggested that a positive Bcl-2 status has a favourable impact on survival: 0.70 (95% confidence interval 0.57 -0.86) in seven studies on stages I -II NSCLC; 0.50 (0.39 -0.65) in eight studies on surgically resected NSCLC; 0.91 (0.76 -1.10) in six studies on any stage NSCLC; 0.57 (0.41 -0.78) in five studies on squamous cell cancer; 0.75 (0.61 -0.93) and 0.71 (0.61 -0.83) respectively for five studies detecting Bcl-2 by immunohistochemistry with Ab clone 100 and for 13 studies assessing Bcl-2 with Ab clone 124; 0.92 (0.73 -1.16) for four studies on small cell lung cancer; 1.26 (0.58 -2.72) for three studies on neuroendocrine tumours. In NSCLC, Bcl-2 expression was associated with a better prognosis. The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value.

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Section: Studies Selection and Characteristicsmentioning

confidence: 99%

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confidence: 99%

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

et al. 2003

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“…A total of 39 studies, published between 1990 and 2002, were found eligible (Kern et al, 1990(Kern et al, , 1994Tateishi et al, 1991Tateishi et al, , 1994Volm et al, 1992Volm et al, , 1993aHarpole et al, 1995aHarpole et al, , b, 1996Giatromanolaki et al, 1996a, b;Pfeiffer et al, 1996;Koukouraki et al, 1997Koukouraki et al, , 2000MacKinnon et al, 1997;Pastorino et al, 1997;Visscher et al, 1997;Yu et al, 1997;Graziano et al, 1998;Greatens et al, 1998;Hsieh et al, 1998;Kim et al, 1998;Kwiatkowski et al, 1998;Nemunaitis et al, 1998;Cantero et al, 1999Cantero et al, , 2000D'Amico et al, 1999;Fu et al, 1999;Moldvay et al, 2000;Schneider et al, 2000;Ardizzoni et al, 2001;Brabender et al, 2001;Liao et al, 2001;Shou et al, 2001;Carbognani et al, 2002;Han et al, 2002;Hirsch et al, 2002;Potti et al, 2002;Selvaggi et al, 2002). Nine of the articles were excluded because identical cohorts of patients were used (studies that were excluded and included were, respectively, references (Cantero et al, 1999) and (Cantero et al, 2000), (Giatromanolaki et al, 1996b;…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

“…The cerbB-2 protein product, p185, is expressed in 20 -30% of nonsmall-cell lung cancers (NSCLC) and particularly in adenocarcinoma (Tateishi et al, 1991;Kern et al, 1994). Numerous studies have suggested that HER-2 expression is associated with advanced or metastatic disease and a poor prognosis (Kern et al, 1990;Tateishi et al, 1991;Harpole et al, 1995a), especially when combined with K-ras mutations (Kern et al, 1994) or Bcl-2 (Kim et al, 1998), whereas others did not (Pfeiffer et al, 1996). Such conflicting results can be explained by the low numbers of patients included in the majority of the studies and by the use of different methods to determine HER-2/neu status.…”

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The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

et al. 2003

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C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with cerbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29 -1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.

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“…RTKs such as erbB (EGF receptor), neu (HER2), kit (stem-cell factor receptor), met (HGF receptor) and others are oncogenes when activated by gene alterations or inappropriately expressed (Shawver, 1999). These RTKs serve as potential therapeutic targets in solid tumors including lung cancer (Levitzki and Gazit, 1995;Ichimura et al, 1996;Giatromanolaki et al, 1996;Olivero et al, 1996;Kim et al, 1998;Nemunaitis et al, 1998;Guddo et al, 1999).…”

Section: Inhibitors Of the Erbb Receptor Familymentioning

confidence: 99%

Clinical impact of novel treatment strategies

Giaccone

2002

Oncogene

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Following two decades of research on the biology of cancer and in particular of lung cancer, we have now a large number of molecular targets that can be utilized to create specific medicines against these cancers. Non-small cell lung cancer represents numerically the most important solid tumor in Western world, and is poorly affected by current therapies, where surgery represents almost the only curative therapy for about 25% of patients who are resectable at diagnosis. An abundant number of targeted therapies are being investigated in NSCLC. Among them are the metalloproteinase inhibitors, several tyrosine kinase inhibitors and several attempts of gene replacement have also been made. Promising results have so far been obtained with some of these approaches, and the outcome of large randomized studies is awaited. Small cell lung cancer (SCLC) represents about 20% of lung carcinomas, and several of the novel approaches that are being attempted for NSCLC, are also being investigated for SCLC. All these novel therapies open a new era of anticancer treatment that will likely complement the currently available therapies in the near future.

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The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients

Cited by 79 publications

References 19 publications

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

Clinical impact of novel treatment strategies

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