ArticleCancer2008
Immunohistochemical markers associated with brain metastases in patients with nonsmall cell lung carcinoma.
Article in Cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Risk factors for brain metastasis in lung cancer: an umbrella review of systematic reviews and meta-analyses.BMJ open · 2025Pooled it
- Augmented expression of Ki-67 is correlated with clinicopathological characteristics and prognosis for lung cancer patients: an up-dated systematic review and meta-analysis with 108 studies and 14,732 patients.Respiratory research · 2018Pooled it
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- Efficacy analysis of brain radiotherapy in EGFR mutation non-small cell lung cancer with brain metastasis: a retrospective study.Discover oncology · 2025Article
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- Article
- EGFR-Driven Mutation in Non-Small-Cell Lung Cancer (NSCLC) Influences the Features and Outcome of Brain Metastases.Journal of clinical medicine · 2023Article
- Article
- Risk factors and a new nomogram for predicting brain metastasis from lung cancer: a retrospective study.Frontiers in oncology · 2023Article
- Clinicopathologic characteristics and diagnostic methods ofTranslational lung cancer research · 2022Article
- [Research Progress on Risk Factors of Brain Metastasis in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- Multiple Primary Lung Cancers With ALK Rearrangement: A Case Report and Literature Review.Frontiers in oncology · 2022Article
- Clinical Biomarkers for Early Identification of Patients with Intracranial Metastatic Disease.Cancers · 2021Review
- High expression of cell adhesion molecule 2 unfavorably impacts survival in non-small cell lung cancer patients with brain metastases.Journal of thoracic disease · 2021Article
- Poor efficacy of anti-programmed cell death-1/ligand 1 monotherapy for non-small cell lung cancer patients with active brain metastases.Thoracic cancer · 2020Article
- Risk factors of metachronous brain metastasis in patients with EGFR-mutated advanced non-small cell lung cancer.BMC cancer · 2020Article
- Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations.Cancer medicine · 2020Article
- Association of neurologic manifestations and CEA levels with the diagnosis of brain metastases in lung cancer patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Article
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- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTo the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC.
methodsThis was a hospital-based, case-control study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases. These patients were compared with a control group of patients who had NSCLC and no evidence of brain metastases. NSCLC was examined for expression levels of Ki-67, caspase-3, vascular endothelial growth factor A (VEGF-A), VEGF-C, E-cadherin, and epidermal growth factor receptor (EGFR) in 54 surgical pathology specimens using immunohistochemistry, and associations were evaluated between those markers and the development of brain metastases.
resultsBrain metastases developed after a median of 12.5 months (range, 1.7-89.4 months) after the diagnosis of NSCLC. A significantly increased risk of developing brain metastases was associated with patients with NSCLC who had primary tumors with high Ki-67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95% CI], 2.4-70.4 [P < .001]), low caspase-3 expression (adjusted OR of 43; 95% CI, 5.3 to >100 [P < .001]), high VEGF-C expression (adjusted OR of 14.6; 95% CI, 2.0 to >100 [P < .001]), and low E-cadherin (adjusted OR of 3.6; 95% CI, 0.9-16.4 [P = .05]). No significant risk was associated with VEGF-A or EGFR expression. High Ki-67 expression also was associated with a shorter overall survival (P = .04).
conclusionsThe results of the current study indicated that patients with NSCLC who had high Ki-67 expression, low caspase-3 expression, high VEGF-C expression, and low E-cadherin expression in their tumors may benefit from close surveillance because they may have an increased risk of developing brain metastases.
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