Bone marrow micrometastases and markers of angiogenesis in esophageal cancer

Background. Tumor angiogenesis is critical for metastasis development. The detection of bone marrow micrometastases may indicate a metastatic phenotype. We aim to establish if the detection of bone marrow micrometaslases associates with elevated markers of angiogenesis and adverse histopathologic features of esophageal cancer. Methods. Bone marrow aspirates from 49 patients with esophageal cancer were assessed and assigned to be positive or negative for micrometastases. Routine histologic assessment of the primary tumor was also undertaken. Circulating and tumor levels of the angiogenic cytokine vascular endothelial growth factor were determined in plasma and tumor homogenate. Intratumor microvessel density was evaluated by counting anti-CD34 positive neovessels. Results. Twenty-two patients were positive for bone marrow micrometastases (44.9%). The detection of micrometastases was associated with advanced T stage (T3/4 vs T1/2; p = 0.023), circumferential margin involvement (p = 0.002) and lymphovascular invasion (p = 0.024). Plasma vascular endothelial growth factor was significantly more elevated in micrometastatic-positive patients than in those without micrometastases (p = 0.018). No difference was noted in tumor vascular endothelial growth factor expression. For adenocarcinomas alone, intratumor microvessel density was significantly higher in micrometastatic positive cases (p = 0.03). This was not the case for squamous cell carcinomas. Conclusions. The detection of bone marrow micrometastases is associated with esophageal tumors of advanced T stage and specifically for adenocarcinomas with tumor vascularity. Plasma vascular endothelial growth factor is elevated in micrometastatic positive cases and might be derived from sources other than the primary tumor. (C) 2004 by The Society of Thoracic Surgeons.