Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: Correlation with vascular endothelial growth factor expression

Abstract

Objectives Lymph node (LN) staging provides critical information in non-small cell lung cancer (NSCLC) patients. Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with VEGF-A/C/D and VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes. Methods Forty NSCLC patients had pre-operative PET-CT and mediastinoscopy. RT-PCR assays for mRNA expression of epithelial markers (CK-7, CEACAM-5 and PLUNC) were performed in selected fluorodeoxyglucose (FDG)-avid lymph nodes. VEGF-A/C/D and VEGF-receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the LNs. Results RT-PCR for CK-7, CEACAM5 or PLUNC indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A/C/D or VEGF-receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months. Conclusions RT-PCR analysis of FDG-avid lymph nodes results in up-staging of patients. Micrometastases correlate with the expression of VEGF in lymph nodes in NSCLC patients. This may reflect the role of lymphangiogenesis in promoting metastases.

Clinical value of nodal micrometastases in patients with non-small cell lung cancer: time for reconsideration?

“…Several reports have shown that the use of immunohistochemistry (IHC) analysis significantly increases the detection rate of occult micrometastases (7). Molecular techniques as polymerase chain reaction (PCR) for p53 and K-ras and reverse transcriptase polymerase chain reaction for CEA, MUC1, CK7, CK19, VEGF and other targets have also been used (3,7,(13)(14)(15). Verhagen et al re-assessed the lymph nodes of patients who had had tumor recurrence after surgery and observed a higher prevalence of micrometastases when using serial node sectioning and immunohistochemistry (16).…”

Morphological Characteristics and Clinical Value of Different Types of Vessels Into a Tissue of Regional Lymph Nodes in Patients With Gastric Cancer

“…Особенности ангиогенеза в регио-нарных лимфатических узлах (РЛУ) у больных РЖ изуче-ны недостаточно. Данные об особенностях ангиогенеза в основном касаются изучения экспрессии VEGF в ткани РЛУ [13,15,17]. При злокачественных новообразованиях ряд авторов наблюдали реактивные изменения со сто-роны РЛУ.…”

“…У пациентов с немелкоклеточным раком легко-го прослеживалась корреляция с наличием метастазов в РЛУ, экспрессией VEGF и рецепторов к нему (VEGF-ре-цептор-3) [15].…”

Diagnosis of lymph node micrometastasis at the pN0 stage of lung adenocarcinoma using a combination of markers

“…Accurate staging is therefore extremely important and can lead to either a more extensive primary therapy to reduce the risk of local recurrence or to systemic adjuvant therapy that eliminates these occult deposits. Conventional HE staining can accurately detect gross nodal metastases in patients with NSCLC, but cannot detect LN micrometastasis (Nwogu et al, 2013). Sensitive immu-nocytochemical tests have been widely used to identify micrometastasis.…”