Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

Breast Cancer Research

Nathalie Blin³  Jean-Paul Thiery³  Brigitte Sigal-Zafrani²  Anne Vincent-Salomon⁴  Claude Nos¹  Jean-Yves Pierga⁵  Valérie Choesmel³ 

[1] Surgery Department, Medical Division, Institut Curie, Paris, France;On behalf of the Institut Curie Breast Cancer Group;UMR144 CNRS, Research Division, Institut Curie, Paris, France;Tumor Biology Department, Medical Division, Institut Curie, Paris, France;Medical Oncology Department, Medical Division, Institut Curie, Paris, France

关键词: micrometastases;    immunodetection;    clinical staging;    breast cancer;    bone marrow;   

Others  :  1118725
DOI  :  10.1186/bcr898

 received in 2004-02-26, accepted in 2004-05-25,  发布年份 2004

【 摘 要 】

Introduction

Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells.

Methods

BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed.

Results

We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods.

Conclusion

These improved methods for the detection of micrometastatic cells in patient BM should help clinicians to predict the clinical status of breast cancer patients at the time of surgery or treatment.

【 授权许可】

   
2004 Choesmel et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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