Elsevier

Surgery

Volume 131, Issue 1, Supplement 1, January 2002, Pages S226-S231
Surgery

Lung Cancer
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,☆☆

https://doi.org/10.1067/msy.2002.119793Get rights and content

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.)

Section snippets

Patients

From May 1996 to November 1997, 58 patients with NSCLC underwent complete resection by a lobectomy combined with formal mediastinal and hilar lymph node dissection. Of these patients, 44 had adenocarcinomas, 13 had squamous cell carcinomas, and 1 had adenosquamous cell carcinoma. They consisted of 33 men and 25 women ranging in age from 26 to 85 (mean, 68.3).

Evaluations regarding the presence of distant metastasis were based on CT scans (brain, chest, and abdomen) and bone scintiscan. None of

Detection of CK-positive cells in bone marrow

CK-positive cells were detected ranging from 1 to 18 cells of 1 × 106 cells examined in the bone marrow aspirates from 27 of 58 patients (47%) with NSCLC. Table I summarizes the relationship between the presence of CK-positive cells in bone marrow and various clinical factors.

. Relationship between the detection of CK-positive cells in the bone marrow and various clinical factors

VariableNo. of patientsNo. of patients with CK-positive cellsP value
Gender
 Male3316.7345
 Female2511
Tumor status
 T1, T24719

Discussion

To identify circulating cancer cells, an immunohistochemical assay4, 5, 6, 10, 11, 12, 13, 14, 15 and molecular approaches such as the sensitive reverse-transcriptase polymerase reaction technique16, 17, 18 have been developed. An immunohistochemical assay based on monoclonal antibodies to CKs is a well-established method for detecting epithelial cells disseminated to the bone marrow. Pantel et al5 reported that the specificity of CK-expression was supported by an overall negative finding on

Acknowledgements

We thank Mr Brian Quinn for his comments on the linguistics of the manuscript.

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    Supported by a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture, Japan.

    ☆☆

    Reprint requests: Kenji Sugio, MD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

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