Micrometastasis in the bone marrow of patients with lung cancer associated with a reduced expression of E-cadherin and β-catenin: Risk assessment by immunohistochemistry

Abstract Background. The presence of disseminated tumor cells in bone marrow is considered to be a premetastatic state, which is called micrometastasis. To evaluate the relationship between micrometastasis and cellular adhesion molecules in the primary lesion, E-cadherin and β-catenin were immunohistochemically investigated. Methods. Fifty-eight patients with non-small cell lung cancer who underwent a complete resection were entered into this study. Tumor cells in bone marrow aspirates were detected by immunohistochemistry using cytokeratin (CK) 18. Immunohistochemical studies of E-cadherin and β-catenin were performed in the corresponding primary tumor. Results. CK-positive cells were detected in the bone marrow aspirates from 27 of 58 patients. A reduced expression of the E-cadherin and β-catenin was found in 16 (27.6%) and in 22 (37.9%) of 58 patients, respectively. In 26 cases with a reduced expression of E-cadherin and/or β-catenin, 16 cases had CK-positive cells, whereas 11 of 32 cases with normal expression of both factors had CK-positive cells ( P = .0392). The patients with micrometastasis demonstrated an earlier recurrence ( P = .0642) and a significantly poorer survival ( P = .0437) than those without such cells. Conclusions. Micrometastasis in the bone marrow might be a significant predictor of poor prognosis, and a reduced expression of E-cadherin and β-catenin are important determinants for the metastatic capability of individual cancer cells. (Surgery 2002;131:S226-31.)