This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, J. Articles by Chan, D. W. Search for Related Content PubMed PubMed Citation Articles by Li, J. Articles by Chan, D. W.

Identification of Biomarkers for Breast Cancer in Nipple Aspiration and Ductal Lavage Fluid

Authors' Affiliations: Departments of ¹ Pathology, ² Surgery and ³ Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland; ⁴ Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and ⁵ Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Requests for reprints: Jinong Li, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287. Phone: 410-502-7874; Fax: 410-502-7882; E-mail: jli{at}jhmi.edu.

Purpose: To establish a comprehensive proteomic approach for biomarker discovery and validation in breast fluid.

Experimental Design: A total of 95 specimens from three institutions were used including 10 nipple aspiration fluid (5 stage I/II cancerous breasts and 5 age-matched healthy controls), 42 ductal lavage fluid from 14 patients with unilateral stage I/II cancer (25 from 9 cancerous breasts and 17 from 7 contralateral breasts), and 42 ductal lavage fluid from 14 high-risk women (multiple ducts repeated lavage). Differentially expressed protein/peptides were discovered by proteomic analysis of training sample, using ProteinChip arrays and surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry, and validated on independently collected testing samples. After protein identification, ELISA was done to confirm the SELDI findings.

Results: We were able to obtain reproducible protein profiles using minimal amount of protein (1 µg) by applying an optimized chip protocol and SELDI. We were able to select cancer-associated biomarkers despite large individual variability by applying both unsupervised and supervised cluster analysis. Furthermore, we were able to train and test candidate biomarkers on independently collected samples and identified one component of a multimarker panel as human neutrophil peptides 1 to 3.

Conclusions: Breast fluid is a rich source of breast cancer biomarkers. In combination with high-throughput novel proteomic profiling technology and multicenter study design, markers that are highly specific to breast cancer can be discovered and validated. Our observations also suggest that persistent elevation of human neutrophil peptide in high-risk women may imply early onset of cancer not yet detectable by current detection method. Proof of this hypothesis requires follow-up on a larger study population.

This article has been cited by other articles:

				H. Zhang and D. W. Chan Cancer Biomarker Discovery in Plasma Using a Tissue-targeted Proteomic Approach Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1915 - 1917. [Full Text] [PDF]

				T. Nakagawa, S. K. Huang, S. R. Martinez, A. N. Tran, D. Elashoff, X. Ye, R. R. Turner, A. E. Giuliano, and D. S.B. Hoon Proteomic Profiling of Primary Breast Cancer Predicts Axillary Lymph Node Metastasis Cancer Res., December 15, 2006; 66(24): 11825 - 11830. [Abstract] [Full Text] [PDF]