Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy

BMC Cancer

Research Article

Hiroji Iwata¹  Hiroko Yamashita²  Shigeru Imoto³  Masakazu Toi⁴  Takayuki Ueno⁵  Yutaka Yamamoto⁶  Shigehira Saji⁷  Hiroyuki Takei⁸  Kazufumi Hisamatsu⁹  Masahiro Sugimoto^1,10  Shinji Ohno^1,11  Norikazu Masuda^1,12  Kenjiro Aogi^1,13  Nobuaki Sato^1,14  Hironobu Sasano^1,15  Katsumasa Kuroi^1,16 

[1]Aichi Cancer Center Hospital, Nagoya, Japan

[2]Breast and Endocrine Surgery, Hokkaido University Hospital, Sapporo, Japan

[3]Department of Breast Surgery, Kyorin University Hospital, 6-20-2 Shinkawa Mitaka, 181-8611, Tokyo, Japan

[4]Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan

[5]Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan

[6]Department of Breast Surgery, Kyorin University Hospital, 6-20-2 Shinkawa Mitaka, 181-8611, Tokyo, Japan

[7]Department of Breast and Endocrine Surgery, Kumamoto University, Kumamoto, Japan

[8]Department of Target Therapy Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan

[9]Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan

[10]Hiroshima City Asa Hospital, Hiroshima, Japan

[11]Institute for Advanced Biosciences Keio University, Yamagata, Japan

[12]National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

[13]National Hospital Organization Osaka National Hospital, Osaka, Japan

[14]National Hospital Organization Shikoku Cancer Center, Ehime, Japan

[15]Niigata Cancer Center Hospital, Niigata, Japan

[16]Tohoku University School of Medicine, Sendai, Japan

[17]Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

关键词: Beclin 1;    Autophagy;    Ki-67;    Breast cancer;    Aromatase inhibitor;    Neoadjuvant endocrine therapy;   

DOI  :  10.1186/s12885-016-2270-9

 received in 2015-02-22, accepted in 2016-03-10,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundNeoadjuvant 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.MethodsIn 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).ResultsImmunoreactivity 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.ConclusionsResults 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.Trial registrationUMIN C000000345 (2006/03/06)

【 授权许可】

CC BY   
© Ueno et al. 2016