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 micrometastases 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.
Spence
Gary M
GM
Department of Thoracic Surgery, Royal Victoria Hospital, Belfast, Northern Ireland. gary.spence@virgin.net
Graham
Alastair N J
AN
Mulholland
Kathleen
K
Maxwell
Perry
P
McCluggage
W Glenn
WG
Sloan
James M
JM
McGuigan
James A
JA
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D001853:Bone Marrow / Q000473:pathology; D001856:Bone Marrow Examination; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D008833:Microcirculation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000097:blood
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A