Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor.

Lee, Jin Soo; Yoon, Anthony; Kalapurakal, Shyla K.; Ro, Jae Y.; Lee, J. Jack; Tu, Nora; Hittelman, Walter N.; Hong, Waun Ki

doi:10.1200/jco.1995.13.8.1893

Cited by 141 publications

(71 citation statements)

References 30 publications

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“…Moreover, the cutoff defining a tumour with a Ki-67 positive staining is often arbitrary and varies according to the investigators, from a few percent to more than 50%. The use of different cutoff points for IHC is of critical importance, as shown by Lee et al (1995). Some investigators selected the cutoff point based on the minimum Pvalue approach, which can lead to seriously biased conclusions (Altman et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

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Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30 -1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

et al. 2004

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“…Moreover, the cutoff in the number of positive cells defining a tumour with Bcl-2 overexpression is often arbitrary and varies according to the investigators, from a few percent to 50%. The use of different cutoff points for IHC is of critical importance, as was shown by Lee et al (1995). Some investigators selected the cutoff point based on the minimum P-value approach, which can lead to seriously biased conclusions (Altman et al, 1994).…”

Section: Discussionmentioning

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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“…These alterations primarily involve amino acid residues contained in the central hydrophobic region of the protein (mostly included in exons 5 ± 8) which mediate the DNAspeci®c transactivating function of p53. Many researchers have focused their investigations on the potential value of p53 immunohistochemistry (IHC) as a prognostic tool (Quinlan et al, 1992;Navone et al, 1993;Carbone et al, 1994;Harpole et al, 1995;Lee et al, 1995;Passlick et al, 1995;Nishio et al, 1996). The utility of IHC as a screening method is dubious, as null mutations (nonsense, frameshift and splice junction mutations) result in the production of shortened polypeptides and most are not recognized by speci®c antibodies because of antigenic site loss (Greenblatt et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…In NSCLC particularly, the clinical value of TP53 alterations as a prognostic tool is still a controversial issue. Some studies indicate that p53 immunohistochemistry is indicative of a poor prognosis (Quinlan et al, 1992;Carbone et al, 1994), while others demonstrate the contrary (Lee et al, 1995). Similarly, the potential role of TP53 mutations is also debatable.…”

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confidence: 99%

TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis

Anta

Jassem²,

Rosell

et al. 1997

Oncogene

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Inactivation of TP53 tumor suppressor gene is the most frequent molecular alteration in NSCLC, involving up to 60% of cases. Furthermore, TP53 mutational spectrum is related to the type of mutagen exposure, as well as racial and/or diet di erences. Nearly 95% of TP53 perturbations a ect codons included within exons 5 ± 8 which encode for almost the entire DNA-binding domain. In this study we addressed the possible prognostic value of the molecular alterations identi®ed in exons 5 ± 8 of the TP53 gene in DNAs from 151 para n-embedded NSCLC sections corresponding to 59 Spanish and 92 Polish stage I-IIIA resected patients. PCR/single-strand conformation polymorphism (SSCP) analysis revealed that the occurrence of TP53 exon 5 ± 8 mutations was 17/59 (29%) in the Spanish cohort and 17/92 (18%) in the Polish group. However, when DNA sequencing analysis was performed, these frequencies were reduced because of the presence of SSCP-false positive, intronic and silent mutations and polymorphisms. Fifteen of the 59 Spanish NSCLC tumors (25%) harbored TP53 mutations a ecting exons 5 ± 8 coding sequences, whereas only 12 of 92 Polish neoplasms (13%) contained alterations in the central hydrophobic region of p53. Our results indicate that the occurrence of TP53 mutations a ecting exon 5 ± 8 coding sequences in some European NSCLC populations may be lower than previously reported, and that the TP53 mutational patterns of these cohorts di er somewhat. The Spanish NSCLC patients contained missense mutations (9/59, 15%) and a relatively high percentage of null mutations (5/59, 8%) while the Polish patients mostly harbored missense mutations (9/92, 10%) and only one tumor contained a null type (1/92, 1%). Moreover, most TP53 missense mutations in the Spanish group were located outside the conserved regions, whereas the same mutations in the Polish group a ected conserved amino acids. Furthermore, the Polish patients harbored a high percentage of G?A transitions (most of them at non-CpG sites), while G?T transversions were predominant in the Spanish group. Our ®ndings suggest that there may be di erent racial or exogenous factors in these two populations which may help to explain both the distinct TP53 mutational pattern and the lower frequency obtained in the Polish group. The presence of missense mutations did not confer a worse clinical outcome in these subsets of NSCLC patients. However, patients whose tumors contained null TP53 gene mutations had a 5 month median disease-free survival time in contrast with 42 months in those patients without mutations (P=0.008). These ®ndings suggest that loss of p53 function may enhance tumor progression in NSCLC patients independently of whether dominant negative TP53 missense mutations are present.

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Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor.

Abstract: These results suggest that high expression of the p53 oncoprotein is a favorable prognostic factor in a subset of patients with NSCLC.

Cited by 141 publications

References 30 publications

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Ki-67 expression and patients survival in lung cancer: 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

TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis

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