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タイトル: | Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy |
著者: | Ueno, Takayuki Saji, Shigehira Sugimoto, Masahiro Masuda, Norikazu Kuroi, Katsumasa Sato, Nobuaki Takei, Hiroyuki Yamamoto, Yutaka Ohno, Shinji Yamashita, Hiroko Hisamatsu, Kazufumi Aogi, Kenjiro Iwata, Hiroji Imoto, Shigeru Sasano, Hironobu Toi, Masakazu |
著者名の別形: | 戸井, 雅和 |
キーワード: | Aromatase inhibitor Autophagy Beclin 1 Breast cancer Ki-67 Neoadjuvant endocrine therapy |
発行日: | 16-Mar-2016 |
出版者: | BioMed Central Ltd. |
誌名: | BMC Cancer |
巻: | 16 |
論文番号: | 230 |
抄録: | Background: Neoadjuvant endocrine therapy (NAE) has been employed to improve surgical outcomes for hormone receptor-positive breast cancers in postmenopausal women. Endocrine responsiveness is estimated by expressions of hormone receptors, but its heterogeneity has been recognized. Autophagy is an evolutionally conserved process associated with cell survival and cell death and has been implicated in cancer treatment. Methods: In order to examine the possible association between autophagy and response to endocrine therapy, we evaluated the status of autophagy-associated markers, beclin 1 and LC3, and apoptosis-associated markers, TUNEL and M30, in pre- and post-treatment specimens from 71 patients in a multicenter prospective study of neoadjuvant exemestane (JFMC34-0601). Results: Immunoreactivity of the autophagy-associated markers, beclin 1 and LC3, in carcinoma cells increased in 14 % and 52 % of the patients, respectively, following the exemestane treatment. These increases were statistically significant (beclin 1, p = 0.016, N = 49; LC3, p < 0.0001, N = 33). The status of M30 immunoreactivity decreased (p = 0.008, N = 47) and TUNEL remained unchanged (N = 53). In addition, tumors with pre-treatment stromal beclin 1 immunoreactivity revealed poor clinical and pathological responses compared with those without stromal beclin 1 immunoreactivity (25 % vs 67 % for clinical response, p = 0.011, N = 51; 0 % vs 41 % for pathological response, p = 0.0081, N = 49). Tumors with positive pre-treatment stromal beclin 1 had a higher baseline Ki-67 labeling index (both hot spot and overall average) than those without (p = 0.042 and 0.0075, respectively, N = 53). Results of logistic regression analyses revealed that stromal beclin 1 was a predictor for clinical and pathological responses while ER, PR, Ki-67, and stromal LC3 expressions were not. Conclusions: Results of our present study demonstrated that beclin 1 and LC3 immunoreactivity increased in carcinoma cells following exemestane treatment and that the status of pre-treatment stromal beclin 1 is associated with higher carcinoma cell proliferation and poor clinical and pathological responses to NAE. |
著作権等: | © 2016 Ueno et al. 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
URI: | http://hdl.handle.net/2433/218382 |
DOI(出版社版): | 10.1186/s12885-016-2270-9 |
PubMed ID: | 26984766 |
出現コレクション: | 学術雑誌掲載論文等 |
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