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- Title
Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure.
- Authors
Kmieciak, Maciej; Payne, Kyle K.; Idowu, Michael O.; Grimes, Margaret M.; Graham, Laura; Ascierto, Maria-Libera; Ena Wang; Xiang-Yang Wang; Bear, Harry D.; Manjili, Masoud H.; Wang, Ena; Wang, Xiang-Yang
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
T cells; CYSTS (Pathology); ENZYME-linked immunosorbent assay; IMMUNOHISTOCHEMISTRY; PRECANCEROUS conditions; BIOLOGICAL transport; BREAST tumors; CELL lines; CELL nuclei; CELL receptors; IMMUNITY; INTERFERONS; DISEASE progression
- Publication
Journal of Translational Medicine, 2011, Vol 9, Issue 1, p35
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/1479-5876-9-35