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 Zhu, W. Articles by Sauter, E. Search for Related Content PubMed PubMed Citation Articles by Zhu, W. Articles by Sauter, E.

Microsatellite Changes in Nipple Aspirate Fluid and Breast Tissue from Women with Breast Carcinoma or Its Precursors

Department of Surgery, Ellis Fischel Cancer Center/University of Missouri, Columbia, Missouri 65212 [W. Z., W. Q., E. S.]; Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania [H. E.]; and Department of Pathology, Montgomery Hospital, Norristown, Pennsylvania [J. L.]

Purpose: Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been identified in a variety of human cancers. The purpose of this prospective study was to determine whether (a) DNA can be isolated from nipple aspirate fluid (NAF) and PCR amplified to large fragments, (b) LOH and MSI are detectable in NAF, and (c) LOH and MSI in tissue and NAF increase with disease progression from precursor lesions to cancer.

Experimental Design: Forty-six matched samples from breast lesions, normal breast, and NAF were microdissected, and DNA was extracted. Eleven microsatellite markers from seven chromosomes that have a high frequency of LOH/MSI in breast cancer were designed and respectively amplified.

Results: LOH and/or MSI were identified in 22 of 46 (48%) breast lesions, including LOH in 8 of 36 (22%) proliferative/papilloma (P/Pap) and 7 of 10 (70%) cancer specimens, whereas MSI was found in 14 of 36 (39%) P/Pap and 6 of 10 (60%) cancer specimens. LOH/MSI loci in which alterations were detected in the 22 tissue specimens were PCR amplified using matched NAF DNA. LOH/MSI was detected in NAF from both P/Pap (5 of 15; 33%) and breast cancer (3 of 7; 43%) samples.

Conclusions: Our findings suggest that (a) DNA from NAF, a physiological fluid collected noninvasively, can be PCR amplified and used to screen for LOH and MSI alterations that are known to be linked to breast cancer, suggesting that this methodology might prove useful for breast cancer screening, and (b) similar to findings in breast tissue, LOH and MSI alterations increase in frequency with disease progression in NAF, which suggests that NAF is a surrogate for breast tissue which has important prognostic implications.

This article has been cited by other articles:

				R. S. Dua, C. M. Isacke, and G. P.H. Gui The Intraductal Approach to Breast Cancer Biomarker Discovery J. Clin. Oncol., March 1, 2006; 24(7): 1209 - 1216. [Abstract] [Full Text] [PDF]

				W. Zhu, W. Qin, P. Bradley, A. Wessel, C. L. Puckett, and E. R. Sauter Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid Carcinogenesis, January 1, 2005; 26(1): 145 - 152. [Abstract] [Full Text] [PDF]