Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy.
Clinical significance of the expression of autophagy-associated marker, beclin 1, in breast cancer patients who received neoadjuvant endocrine therapy.
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DOI：
10.1186/s12885-016-2270-9
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发表时间：
2016-03-16
期刊：
影响因子：
3.8
通讯作者：
Toi M
中科院分区：
文献类型：
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作者：
Ueno T;Saji S;Sugimoto M;Masuda N;Kuroi K;Sato N;Takei H;Yamamoto Y;Ohno S;Yamashita H;Hisamatsu K;Aogi K;Iwata H;Imoto S;Sasano H;Toi M
新辅助内分泌治疗（NAE）已被用于改善绝经后女性激素受体阳性乳腺癌的手术结局。内分泌反应性是通过激素受体的表达来估计的，但其异质性已被认识到。自噬是与细胞存活和细胞死亡相关的进化保守的过程，并且已经涉及癌症治疗。为了研究自噬与内分泌治疗反应之间的可能关联，我们在一项新辅助治疗阿司美坦的多中心前瞻性研究（JFMC 34 -0601）中，评价了71例患者治疗前和治疗后标本中自噬相关标志物beclin 1和LC 3以及凋亡相关标志物TUNEL和M30的状态。自噬相关标志物beclin 1和LC 3在癌细胞中的免疫反应性在阿司美坦治疗后分别在14%和52%的患者中增加。这些增加具有统计学显著性（beclin 1，p = 0.016，N = 49; LC 3，p < 0.0001，N = 33）。M30免疫反应性状态降低（p = 0.008，N = 47），TUNEL保持不变（N = 53）。此外，与无基质beclin 1免疫反应性的肿瘤相比，具有治疗前基质beclin 1免疫反应性的肿瘤显示出较差的临床和病理学反应（临床反应为25% vs 67%，p = 0.011，N = 51;病理学反应为0% vs 41%，p = 0.0081，N = 49）。治疗前间质beclin 1阳性的肿瘤的基线Ki-67标记指数（热点和总体平均值）高于未阳性的肿瘤（分别为p = 0.042和0.0075，N = 53）。Logistic回归分析结果显示，间质Beclin 1是临床和病理反应的预测因子，而ER、PR、Ki-67和间质LC 3表达不是。我们目前的研究结果表明，贝伐美坦治疗后，癌细胞中的beclin 1和LC 3免疫反应性增加，并且治疗前基质beclin 1的状态与癌细胞增殖较高以及对NAE的临床和病理反应较差相关。UMIN C 000000345（2006/03/06）本文的在线版本（doi：10.1186/s12885-016-2270-9）包含补充材料，可供授权用户使用。
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. 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). 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. 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. UMIN C000000345 (2006/03/06) The online version of this article (doi:10.1186/s12885-016-2270-9) contains supplementary material, which is available to authorized users.