乳腺癌新辅助化疗疗效与PI3K／mTOR通路的相关性分析

Relationship between the response of breast cancer to neoadjuvant chemotherapy and PI3K/mTOR pathway

目的观察P13K／mTOR通路状态与乳腺癌新辅助化疗疗效之间的关系。方法对2009年1月至2010年11月在北京大学第一医院乳腺疾病中心接受4～6个周期包含紫杉方案新辅助化疗的105例乳腺癌患者资料进行回顾性分析。用免疫组织化学方法检测新辅助化疗前肿瘤病灶PTEN、p-AKT（Ser473）和p-mTOR（Ser2448）的表达情况，用术后病理评价新辅助化疗疗效，病理学反应级别为G4、病理完全缓解（PCR）则认为化疗有效。通过x2检验、Fisher精确概率法和双边Logistic回归探讨上述指标与新辅助化疗疗效之间的相关性。结果105例患者中新辅助化疗有效率为58．1％（61／105），其中PCR占27．6％（29／105）。PTEN、p-AKT和p-Ⅱ汀0R的阳性表达率分别为52．4％（55／105）、68．6％（72／105）、43．8％（46／105）。x2检验、Fisher精确概率法分析表明p-mTOR与新辅助化疗疗效相关（P=0．003），与获得PCR相关（P=0．001）；双边Logistic回归表明p-mTOR是新辅助化疗疗效和获得PCR（均P〈0．01）的独立预测指标。p-AKT与p-roTOR表达水平差异有统计学意义（P=0．000）。p-AKT与PR表达差异同样有统计学意义（P=0．035）。结论p-mTOR状态对于包含紫杉方案的新辅助化疗有预测意义，高表达患者疗效差，低表达患者更多地从化疗中获益。

Objective To explore the relationship between the status of PI3K/mTOR pathway and the therapeutic efficacies of neoadjuvant chemotherapy for breast cancer. Methods A total of 105 patients receiving 4 -6 cycles of taxane-based neoadjuvant chemotherapy at our centre between January 2009 and November 2010 were recruited into this retrospective study. The expressions of PTEN, p-AKT （Sev473） and p-mTOR （Ser2448） were detected by immunohistochemistry before neoadjuvant chemotherapy. We employed pathology to evaluate the therapeutic efficacies and considered complete response （G4） ＆ pathologic complete response （PCR） as efficacious. Fourfold table Chi-square test and binary Logistic regression were used to analyze the relationship between the above features and therapeutic efficacies. Results The overall efficacy rate of neoadjuvant chemotherapy was 58. 1% （ 61/105 ） and the PCR rate 27.6% （29/105）. The positive expression rates of PTEN, p-AKT and p-roTOR were 52.4% （57/105）, 68. 6% （72/105） and 43.8% （46/105） respectively. Fourfold table Chi-square test showed the difference between p-mTOR and therapeutic efficacy was significant statistically （ P = 0. 003 ） and also the difference between p- roTOR and PCR （ P = 0. 001 ） . Binary Logistic regression showed the difference between p-mTOR and therapeutic efficiency was significant statistically, and also the difference between p-mTOR and PCR （both P 〈0. 01 ）. The differential expressions of p-mTOR and p-AKT were statistically significant （P = 0. 000） and so were those of p-AKT and PR （ P = 0. 035 ）. Conclusions The status of p-mTOR has predictive values for taxane-based neoadjuvant chemotherapy. The patients with a low level of p-mTOR are more responsive to thermotherapy while those with a high level of p-mTOR have a worse efficacy.