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Chromosomal Alterations Associated with the Transition from In Situ to Invasive Breast Cancer

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Ductal carcinoma in situ (DCIS) is a preinvasive lesion of the breast with an inherent but nonobligatory tendency for progression to invasive breast cancer. Although the transition from in situ to invasive disease is critical to the development of breast cancer, molecular and biological changes responsible for this transition are not well characterized.

Methods

Chromosomal alterations at 26 regions were assayed in 66 DCIS lesions and 111 invasive ductal carcinomas. Levels and patterns of allelic imbalance (AI) were compared between grade 1 DCIS and well-differentiated breast carcinomas, and between grade 3 DCIS and poorly differentiated invasive breast carcinomas, using Fisher’s exact and Student’s t-tests.

Results

Levels of AI were significantly lower (P < 0.01) in grade 1 DCIS (11.9%) compared to well-differentiated carcinomas (19.2%), but were not significantly different between grade 3 DCIS and poorly differentiated tumors. No significant differences were detected at any of the 26 chromosomal regions between low-grade DCIS and invasive tumors; however, AI events at chromosomes 1p36, 11q23, and 16q11–q22 could discriminate high-grade in situ from invasive disease.

Conclusion

Lower levels of AI in low-grade in situ compared with invasive disease may reflect the protracted time to progression associated with low-grade DCIS. Increased levels of AI at chromosomes 1p36 and 11q23 in poorly differentiated carcinomas may harbor genes associated with invasiveness, while loss of chromosome 16q11–q22 may prevent the transition from in situ to invasive disease. Further characterization of these changes may provide molecular assays to identify DCIS lesions with invasive potential as well as targets for molecular therapeutics.

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Acknowledgements

This research was supported by a grant from Susan G. Komen for the Cure (BCTR0600366) to R.E.E. and the United States Department of Defense (Military Molecular Medicine Initiative MDA W81XWH-05-2-0075). The opinion and assertions contained herein are the private views of the authors and are not to be construed as official or as representing the views of the Department of the Army or the Department of Defense.

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Authors and Affiliations

  1. Clinical Breast Care Project, Henry M. Jakcon Foundation for the Advancement of Military Medicine, 620 Seventh Street, Windber, PA, 15963, USA

    Rachel E. Ellsworth PhD

  2. Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA, 15963, USA

    Rachel E. Ellsworth PhD & Darrell L. Ellsworth PhD

  3. Clinical Breast Care Project, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW, Washington, DC, 20307, USA

    Amy Vertrees MD, Jeffrey A. Hooke MD & Craig D. Shriver MD

  4. Invitrogen, 1600 Faraday Avenue, Carlsbad, CA, 92008, USA

    Brad Love PhD

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  1. Rachel E. Ellsworth PhD
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  2. Amy Vertrees MD
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  3. Brad Love PhD
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  4. Jeffrey A. Hooke MD
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  5. Darrell L. Ellsworth PhD
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  6. Craig D. Shriver MD
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Correspondence to Rachel E. Ellsworth PhD.

Additional information

Address reprints requests to: Ms. Kerri Cronin, Clinical Breast Care Project, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW, Washington, DC 20307, USA; E-mail: kerri.cronin@amedd.army.mil.

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Ellsworth, R.E., Vertrees, A., Love, B. et al. Chromosomal Alterations Associated with the Transition from In Situ to Invasive Breast Cancer. Ann Surg Oncol 15, 2519–2525 (2008). https://doi.org/10.1245/s10434-008-0051-7

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  • DOI: https://doi.org/10.1245/s10434-008-0051-7

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