ABSTRACT
BACKGROUND: The tumor microenvironment plays a critical role in tumor growth and spreading. Tumor-associated macrophages (TAM) make up a large proportion of the tumor mass and are one of the main producers of CC-chemokine ligand 18 (CCL18), which is believed to carry out important functions in the immunological interactions that promote tumor progression. MATERIALS AND METHODS: Cytokines/chemokines were measured in bronchoalveolar lavage (BAL) from the tumor site and serum before and after resection in patients with proven non-small cell lung cancer (NSCLC). RESULTS: CCL18 concentrations in BAL positively correlated with the radiologically determined tumor volume (r=0.72, p=0.0003) in NSCLC. In addition, tumors with lymph-node metastasis exhibited significantly higher CCL18 concentrations in BAL (p=0.049) than those without. Serum CCL18 concentrations did not differ significantly before and after tumor resection. CONCLUSION: The increased release of CCL18 with greater tumor size is most likely due to the accompanied growth of leukocyte infiltrate. With previous findings taken into account, this could be one factor contributing to tumor invasiveness and particularly lymphatic spread in patients with larger tumors.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Chemokines, CC/metabolism , Gene Expression Regulation, Neoplastic , Lung Neoplasms/metabolism , Lymph Nodes/metabolism , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid , Gene Expression Profiling , Humans , Lymphatic Metastasis , Macrophages/metabolism , Neoplasm Invasiveness , Neoplasms/metabolism , Prospective Studies , Tumor MicroenvironmentABSTRACT
INTRODUCTION: Microscopic examination of histologic slides or cytologic specimens of mediastinal lymph node samples obtained by diagnostic mediastinoscopy or endobronchial ultrasound-guided fine-needle aspiration (EBUS-TBNA) is routinely used for the staging of lung cancer patients. Therefore, we explored whether the detection of tumor-associated mRNA in lymph node samples from patients with suspected lung cancer adds diagnostic accuracy to conventional histopathological staging. METHODS: We examined 202 lymph nodes obtained by EBUS-TBNA or mediastinoscopy from 89 patients with lung cancer. Lymph node samples from patients with nonmalignant disease were available as controls (60 samples from 31 patients). Real-time quantitative mRNA analysis was performed for melanoma antigen-A genes (MAGE-A 1-6, MAGE-A 12) using a LightCycler 480 instrument. RESULTS: MAGE transcript levels in control and cancer patients differed widely, and the 95% confidence interval served to define the threshold between negative and positive samples. MAGE 1 to 6 transcripts were detected in 35 of 122 (28.7%) lymph nodes obtained by EBUS-TBNA and 16 of 80 (20.0%) lymph nodes obtained by mediastinoscopy. MAGE 12 transcripts were detected in 10 of 122 (8.2%) lymph nodes obtained by EBUS-TBNA and 9 of 80 (11.3%) lymph nodes obtained by mediastinoscopy. Although the accuracy of histopathological diagnosis after EBUS-TBNA and mediastinoscopy was 69.6% and 84.1%, respectively, it increased to 81.2% and 86.4%, respectively, when combined with MAGE-quantitative polymerase chain reaction. CONCLUSIONS: The combination of EBUS-TBNA and MAGE-quantitative polymerase chain reaction increases the accuracy of tumor cell detection to the level seen with mediastinoscopy.
