Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small-cell lung cancer.

Apolinario, Rosa María Cáceres; Valk, Paul van der; Jong, Johannes S. de; Devillé, W.; Ark-Otte, J. van; Dingemans, Anne Marie C.; Mourik, Johan C. van; Postmus, P.E.; Pinedo, H. M.; Giaccone, Giuseppe

doi:10.1200/jco.1997.15.6.2456

Cited by 138 publications

(80 citation statements)

References 30 publications

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“…In our study, contrary to what was observed in other tumour types (Silvestrini et al, 1994;Krajewski et al, 1995;Apolinario et al, 1997), no relationship was found between p53 and bax or bcl-2 protein expression, i.e., cases not expressing p53 did not present any clear upregulation of bax or downregulation of bcl-2. This finding could imply that bax or bcl-2 might be regulated by mechanisms other than p53, as already reported with regard to colorectal tumours (De Angelis et al, 1998) and other tumour types including breast cancer , non-small-cell lung cancer (Apolinario et al, 1997), squamous cell carcinoma of the larynx (Fracchiolla et al, 1999) and of the oral cavity (Costa et al, 1998).…”

Section: Discussioncontrasting

confidence: 99%

“…This finding could imply that bax or bcl-2 might be regulated by mechanisms other than p53, as already reported with regard to colorectal tumours (De Angelis et al, 1998) and other tumour types including breast cancer , non-small-cell lung cancer (Apolinario et al, 1997), squamous cell carcinoma of the larynx (Fracchiolla et al, 1999) and of the oral cavity (Costa et al, 1998). Generally, no relationship was observed between clinical outcome and p53/bax or p53/bcl-2 staining patterns, except for a high response rate (42%) in patients with p53 -/bax -tumours.…”

Section: Discussionsupporting

confidence: 68%

“…Among the different approaches to evaluate cell susceptibility to the activation of apoptosis, we focused on the expression of two negative and positive regulatory proteins, bcl-2 and bax, whose immunocytochemical determination proved to be feasible on archival specimens and associated with tumour progression and treatment response in different clinical situations involving various tumour types (Krajewski et al, 1995;Barretton et al, 1996;Apolinario et al, 1997;Bonetti et al, 1998;Silvestrini et al, 1998;Tai et al, 1998;Daidone et al, 1999;Ogura et al, 1999;Sturm et al, 1999). Bax represents a pro-apoptotic member of the bcl-2 family which controls important checkpoints during the apoptotic process and whose transcriptional activation is induced by wild-type p53.…”

Section: Discussionmentioning

confidence: 99%

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Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

Paradiso¹,

Simone²,

Lena³

et al. 2001

Br J Cancer

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SummaryThe clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short-and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

Paradiso¹,

Simone²,

Lena³

et al. 2001

Br J Cancer

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“…Ten were excluded (Giatromanolaki et al, 1996a(Giatromanolaki et al, ,b, 1997Koukourakis et al, 1997Koukourakis et al, , 1999Koukourakis et al, , 2000aKakolyris et al, 1999) because identical cohorts of patients were used in other selected publications. In the eight remaining eligible studies (Apolinario et al, 1997;Kawaguchi et al, 1997;Pastorino et al, 1997;Duarte et al, 1998;Ohta et al, 1999;O'Byrne et al, 2000;Han et al, 2001;Hasegawa et al, 2001), published between 1996 and 2001, the total …”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

et al. 2002

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In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a metaanalysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16 -2.84), CD34 (HR: 1.99; 95% CI: 1.53 -2.58) or CD31 (HR: 1.80; 95% CI: 1.10 -2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

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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%

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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Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small-cell lung cancer.

Cited by 138 publications

References 30 publications

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

The role of microvessel density on the survival of patients with 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

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