Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2 in stage I non–small-cell lung cancer

Han, Helen; Landreneau, Rodney J.; Santucci, Tibetha; Tung, Ming Y.; Macherey, Robin S.; Shackney, Stanley E.; Sturgis, Charles D.; Raab, Stephen S.; Silverman, Jan F.

doi:10.1053/hupa.2002.30183

Cited by 87 publications

(67 citation statements)

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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;…”

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confidence: 99%

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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Section: Studies Selection and Characteristicsmentioning

confidence: 99%

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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“…5 Although tumor stage has a significant role in predicting survival, patients with the same stage may have different outcomes, 6 urging the need for new reliable predictors of the disease relapse and survival. 6,7 These markers would be of value in optimizing the medical management of patients at high risk for disease recurrence and/or short survival.…”

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confidence: 99%

“…8,9 Although HER2/neu has been studied most extensively in the breast, 10,11 there is only a limited amount of information regarding its prognostic value in lung cancer. 7 p53 is a tumor suppressor gene, located on chromosome 17p13. 12 The product of this gene is a nuclear protein involved in the control of cell cycle activation, apoptosis, and maintenance of genomic stability.…”

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confidence: 99%

“…12 The altered protein from the mutant gene has an extended half-life and can be detected with immunohistochemical techniques. 7,13 Loss of tumor suppressor function of p53 has been identified in different types of human cancer including cancer of the lung. 7,14,15 Vascular endothelial growth factor (VEGF) is an angiogenic factor, produced by the tumor cells to stimulate intratumoral microvessel proliferation (neoangiogenesis).…”

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confidence: 99%

“…7,13 Loss of tumor suppressor function of p53 has been identified in different types of human cancer including cancer of the lung. 7,14,15 Vascular endothelial growth factor (VEGF) is an angiogenic factor, produced by the tumor cells to stimulate intratumoral microvessel proliferation (neoangiogenesis). Tumor angiogenesis contributes to the metastatic process by providing large numbers of leaking blood vessels for vascular invasion.…”

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Prognostic significance of HER2/neu, p53, and vascular endothelial growth factor expression in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung

et al. 2004

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In this study, we investigated the prognostic value of HER2/neu, p53, and vascular endothelial growth factor in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. We studied 100 patients and consisted of 50 cases with conventional adenocarcinoma and 50 cases with bronchioloalveolar carcinoma (32 nonmucinous and 18 mucinous subtypes). Representative sections were immunostained for HER2/neu, p53, and vascular endothelial growth factor. Positivity was scored quantitatively by three observers and correlated with multiple prognostic parameters including survival. In the conventional adenocarcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 19/50 (38%), 32/50 (64%), 33/50 (66%), respectively. In this group, p53 showed a significant correlation with recurrence while vascular endothelial growth factor correlated with angiolymphatic invasion (Po0.05). HER2/neu, p53, and vascular endothelial growth factor expression was associated with significantly shorter survival (log rank, Po0.05). Patient whose tumors coexpressed both p53 and HER2/neu had the worst outcome. In the bronchioloalveolar carcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 9/50 (18%), 3/50 (6%) and 12/50 (24%), respectively which was significantly less than in conventional adenocarcinoma (Po0.05). HER2/neu positivity showed a significant correlation with shorter survival (log rank, Po0.05) in nonmucinous type. In conclusion, vascular endothelial growth factor was associated with angiolymphatic invasion and poor prognosis in conventional adenocarcinoma. Also, in conventional adenocarcinoma, p53, and HER2/neu expression appeared to be poor prognostic markers, while in bronchioloalveolar carcinoma, only HER2/neu was associated with a poorer prognosis. This immunostaining pattern suggests that conventional adenocarcinoma has different molecular abnormalities than bronchioloalveolar carcinoma.

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Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2 in stage I non–small-cell lung cancer

Cited by 87 publications

References 19 publications

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

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

Prognostic significance of HER2/neu, p53, and vascular endothelial growth factor expression in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung

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