HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abdul-Rasool, S Articles by Hanekom, G S Search for Related Content PubMed PubMed Citation Articles by Abdul-Rasool, S Articles by Hanekom, G S Pubmed/NCBI databases Medline Plus Health Information Breast Cancer

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes

¹ Department of Clinical Laboratory Sciences, Division of Haematology, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital and National Health Laboratory Services of South Africa, Cape Town, South Africa
² Department of Surgery, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital and National Health Laboratory Services of South Africa, Cape Town, South Africa
³ Department of Anatomical Pathology, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital and National Health Laboratory Services of South Africa, Cape Town, South Africa
⁴ Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital and National Health Laboratory Services of South Africa, Cape Town, South Africa

Correspondence to:
Dr S Abdul-Rasool
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; srasool{at}cormack.uct.ac.za Background and objectives: In patients with breast cancer (BC), the sentinel node (SN) is the first node in the axillary basin that receives the primary lymphatic flow and can be used to accurately assess the axillary nodal status without removal of the axillary contents. Currently, histology and/or immunohistochemistry are the routine methods of SN analysis. The primary objective of this study was to develop a reproducible reverse transcription (RT) PCR assay, with emphasis on achieving high specificity for accurate detection of BC micrometastases in the SN. To correct for the heterogeneity of BC cells, a multimarker approach was followed, with the further aim of improving the detection rate of the assay.

Methods: In total, 73 markers were evaluated, of which 7 were breast epithelial markers and 66 were either cancer testis or tumour associated antigens. Twelve BC cell lines and 30 SNs (from 30 patients) were analysed using RT-PCR to determine the in vitro and in vivo detection rates for each of the markers. In addition, 20 axillary nodes obtained from a patient with brain death were used as controls to optimise the PCR cycle numbers for all the markers.

Results: Of the 30 SNs, 37% (11/30) were positive on haematoxylin and eosin analysis. Extensive immunohistochemical (IHC) analyses of the haematoxylin and eosin negative nodes confirmed the presence of very small numbers of BC cells in an additional 40% (12/30) of SNs. Molecular analysis with the hMAM-A alone identified metastases in 70% (21/30) of SNs. Using MAGE-A3 in combination with hMAM-A identified metastases in 90% (27/30) of patients. Seven SNs (23%) were negative for micrometastases (with haematoxylin and eosin and IHC) but RT-PCR positive for either hMAM-A or MAGE-A3.

Conclusions: As IHC analysis resulted in a 77% detection rate compared with 37% for haematoxylin and eosin analysis, we consider that IHC is essential in order not to miss SN micrometastases. Molecular analysis with hMAM-A and MAGE-A3 allows detection of BC micrometastases with a 90% detection rate. However, the clinical value of histologically negative but RT-PCR positive SNs can only be determined with long term follow up.

Abbreviations: BC, breast cancer; CTA, cancer testis antigen; hMAM; IHC, immunohistochemical; RT, reverse transcription; SN, sentinel lymph node

Keywords: breast cancer; RT-PCR; sentinel lymph node; specificity; micrometastases

This article has been cited by other articles:

				W. Yang, D. Luo, S. Wang, R. Wang, R. Chen, Y. Liu, T. Zhu, X. Ma, R. Liu, G. Xu, et al. TMTP1, a Novel Tumor-Homing Peptide Specifically Targeting Metastasis Clin. Cancer Res., September 1, 2008; 14(17): 5494 - 5502. [Abstract] [Full Text] [PDF]

				M. Lacroix Significance, detection and markers of disseminated breast cancer cells Endocr. Relat. Cancer, December 1, 2006; 13(4): 1033 - 1067. [Abstract] [Full Text] [PDF]