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Abstract
BackgroundIn non-small cell lung cancer (NSCLC), nodal metastasis is an adverse prognostic factor. Several mediating factors have been implied in the development of nodal metastases and investigated for predictive and prognostic properties in NSCLC. However, study results differ. In this structured review and meta-analysis we explore the published literature on commonly recognized pathways for molecular regulation of lymphatic metastasis in NSCLC.MethodsA structured PubMed search was conducted for papers reporting on the expression of known markers of lymhangiogenesis in NSCLC patients. Papers of sufficient quality, presenting survival and/or correlation data were included.ResultsHigh levels of vascular endothelial growth factor C (VEGF-C, HR 1.57 95% CI 1.34–1.84) and high lymphatic vascular density (LVD, HR 1.84 95% CI 1.18–2.87) were significant prognostic markers of poor survival and high expression of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR3) and LVD was associated with lymph node metastasis in NSCLC.ConclusionLymphangiogenic markers are prognosticators of survival and correlate with lymph node metastasis in NSCLC. Their exact role and clinical implications should be further elucidated.
Highlights
Lung cancer is estimated to have the second highest incidence of all cancers in US women and men [1]
High levels of vascular endothelial growth factor C (VEGF-C, hazard ratios (HR) 1.57 95% confidence intervals (CI) 1.34–1.84) and high lymphatic vascular density (LVD, HR 1.84 95% CI 1.18–2.87) were significant prognostic markers of poor survival and high expression of Vascular endothelial growth factors (VEGF)-C, vascular endothelial growth factor receptor 3 (VEGFR3) and Lymphatic vessel density (LVD) was associated with lymph node metastasis in Non-small cell lung cancer (NSCLC)
Subgroup analyses reporting on VEGF-C and survival in 4 studies of adenocarinomas (n = 317) and 5 studies of stage I NSCLC (n = 542) revealed HRs of 1.45 and 1.56, respectively (Fig 2A)
Summary
Lung cancer is estimated to have the second highest incidence of all cancers in US women and men [1]. Stage I comprises small localized tumors, while stages II-IIIA represent larger tumors with or without nodal metastasis [3]. The five-year-survival for stage IA, IB, IIA, IIB and IIIA lung cancer is 65–81%, 54–72%, 46–59%, 46–47% and 33–38% respectively [4,5,6]. Stage IIIB and IV lung cancers are not considered for surgery and have an abysmal prognosis [4,5,6]. Non-small cell lung cancer (NSCLC) represent >80% of all lung cancer cases [7]. In non-small cell lung cancer (NSCLC), nodal metastasis is an adverse prognostic factor.
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