Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure

Authors

Maciej Kmieciak, Virginia Commonwealth University
Kyle K. Payne, Virginia Commonwealth UniversityFollow
Michael O. Idowu, Virginia Commonwealth UniversityFollow
Margaret M. Grimes, Virginia Commonwealth UniversityFollow
Laura Graham, Virginia Commonwealth UniversityFollow
Maria-Libera Ascierto, National Institutes of Health
Ena Wang, National Institutes of Health
Xiang-Yang Wang, Virginia Commonwealth UniversityFollow
Harry D. Bear, Virginia Commonwealth UniversityFollow
Masoud H. Manjili, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2011

Journal/Book/Conference Title

Journal of Translational Medicine

Volume

2011

DOI

10.1186/1479-5876-9-35

Comments

Originally published by http://dx.doi.org/10.1186/1479-5876-9-35

Date of Submission

September 2014

Abstract

Background Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.

Methods We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ Rα in the tumors was determined by immunohistochemistry analysis of paraffin-embedded tissues.

Results We determined that majority of (10 of 12) patients with HER-2/neu negative breast cancer had HER-2/neu-specific IFN-γ producing T cell responses which was stronger than those in patients with HER-2/neu positive tumors. Such immune responses were associated with nuclear translocation of IFN-γ Rα in their tumor cells. Patient with DCIS also showed HER-2/neu-specific T cell responses.

Conclusion These data suggest that conducting retrospective studies in patients with HER-2/neu negative breast cancers and prospective studies in patients with HER-2/neu positive DCIS can determine whether HER-2/neu negative invasive carcinomas arise from HER-2/neu positive DCIS under the immune pressure.

Rights

© 2011 Kmieciak et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Is Part Of

VCU Microbiology and Immunology Publications