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DJ-1 protein expression as a predictor of pathological complete remission after neoadjuvant chemotherapy in breast cancer patients

  • Preclinical study
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Abstract

Parkinson’s disease is associated with DJ-1/Parkinson protein 7 dysfunction. In contrast, hyperactivity of DJ-1 increases the resistance of cancer cells to apoptosis. Recent genetic studies showed that, in addition to apoptosis pathways, DJ-1 is also involved in cellular defense against reactive oxygen species. The activity of apoptotic and cellular defense pathways is key in determining drug sensitivity. DJ-1 overexpression is associated with various cancers. However, we previously found that there were approximately 50 % patients with breast cancers that expressed low levels of DJ-1 protein, despite mRNA upregulation. Furthermore, low DJ-1 expression was a significant predictor of poor clinical outcome in these patients. This study aimed to determine the association between low DJ-1 protein expression and pathological complete remission (pCR) after neoadjuvant chemotherapy in breast cancer patients. Expression of DJ-1 in pre-therapeutic needle biopsies and surgical specimens obtained from 205 breast cancer cases that received neoadjuvant chemotherapy was determined using immunohistochemistry and in situ hybridization. Chemotherapy comprised epirubicin/cyclophosphamide taxane-based regimens with or without the inclusion of trastuzumab. Univariate and multivariate analyses were used to evaluate the predictive value of DJ-1 on pCR. Low DJ-1 protein expression was detected in 45.3 % (93/205) of all breast cancer cases and in 79.6 % (39/49) of pCR cases, irrespective of maintained mRNA levels. DJ-1 expression [hazard ratio (HR): 1.36; 95 % confidence interval (CI): 1.01–1.84] and HER2 status (HR: 0.84; 95 % CI: 0.62–1.14), in contrast to histological grade, hormone receptors status, Ki-67 labeling index, and intrinsic subtype, were significant predictors of pCR. Low DJ-1 expression predicted pCR in luminal A (P = 0.0004), luminal B (P = 0.0194), and triple negative (P = 0.0143) subtypes breast cancer patients and in patients receiving additional trastuzumab treatment (P = 0.008). In conclusion, low DJ-1 protein expression is a significant predictor of pCR after neoadjuvant chemotherapy in breast cancer patients.

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Acknowledgments

We thank Ms. Kozue Suzuki for technical assistance and Ms. Miho Morita for secretarial assistance. This study was supported by the Foundation for Promotion of Cancer Research (Keiichi Iwaya, and Osamu Matsubara), Ministry of Defense Grants (Keiichi Iwaya and Osamu Matsubara), Grant-in-aid for Scientific Research (KAKENHI24590457) (Keiichi Iwaya), and the National Cancer Research and Development Fund (23-A-11) (Keiichi Iwaya).

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Takahiko Kawate, Keiichi Iwaya, Ryoko Kikuchi & Osamu Matsubara

  2. Department of Breast Oncology, Tokyo Medical University, Tokyo, 160-0023, Japan

    Takahiko Kawate, Keiichi Iwaya, Hiroshi Kaise, Miki Oda & Norio Kohno

  3. Department of Pathology, Tokyo Medical University, Tokyo, 160-0023, Japan

    Eiichi Sato

  4. Departments of Pathology and Laboratory Medicine, National Defense Medical College, Saitama, 359-8513, Japan

    Sadayuki Hiroi

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  1. Takahiko Kawate
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  2. Keiichi Iwaya
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Correspondence to Keiichi Iwaya.

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Kawate, T., Iwaya, K., Kikuchi, R. et al. DJ-1 protein expression as a predictor of pathological complete remission after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Res Treat 139, 51–59 (2013). https://doi.org/10.1007/s10549-013-2523-0

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  • DOI: https://doi.org/10.1007/s10549-013-2523-0

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