ABSTRACT
Detection of micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of esophageal cancer patients. Bone marrow and peripheral blood samples were obtained from 52 squamous esophageal cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor (VEGF) and cyclin D1 was examined in the primary tumors. Cytokeratin-positive cancer cells were observed in the bone marrow of 13 (25%) out of 52 patients. Among them, three patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with lymph node metastasis (pN) but not associated with depth of tumors (pT). Detection of bone marrow micrometastasis was significantly correlated with VEGF expression of the primary tumors. Cumulative survival of patients with bone marrow micrometastasis was significantly lower than that of patients without it (p=0.0008). Hematogenous recurrence was more frequent in patients with bone marrow micrometastasis than in those without it (p=0.0004). Three patients who had local or dissemination recurrence did not have bone marrow micrometastasis. Detection of cancer cells in the bone marrow might be an indicator of early hematogenous metastasis in esophageal cancer patients. Intensive postoperative chemotherapy seems to be indicated for these patients.
Subject(s)
Bone Marrow Neoplasms/secondary , Esophageal Neoplasms/pathology , Immunomagnetic Separation/methods , Aged , Antigens, Neoplasm/metabolism , Bone Marrow Neoplasms/metabolism , Esophageal Neoplasms/metabolism , Female , Humans , Keratin-19 , Keratins/metabolism , Male , Middle Aged , Serpins/metabolism , Survival AnalysisABSTRACT
BACKGROUND: Micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients after surgery. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of gastric cancer patients. METHODS: Bone marrow and peripheral blood samples were obtained from 53 gastric cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor and erbB-2/HER2 was examined in the primary tumors. RESULTS: Cytokeratin-positive cancer cells were observed in the bone marrow of 16 (30%) of 53 patients. Among them, two patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with the depth of invasion and lymph node metastasis but was not associated with peritoneal dissemination. Detection of bone marrow micrometastasis was not correlated with vascular endothelial growth factor or HER2 expression in the primary tumors. Four patients with micrometastasis had recurrence in the liver or lungs, but this did not occur in patients without micrometastasis. CONCLUSIONS: Detection of cancer cells in the bone marrow might be an indicator of postoperative hematogenous metastasis in gastric cancer patients.
