The nuclear transcription factor κB/bcl-2 pathway correlates with pathologic complete response to doxorubicin-based neoadjuvant chemotherapy in human breast cancer
The nuclear transcription factor κB/bcl-2 pathway correlates with pathologic complete response to doxorubicin-based neoadjuvant chemotherapy in human breast cancer
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DOI：
10.1158/1078-0432.ccr-05-0885
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发表时间：
2005-12-01
影响因子：
11.5
通讯作者：
Sahin, AA
中科院分区：
文献类型：
--
作者：
Buchholz, TA;Garg, AK;Sahin, AA
目的：参与细胞凋亡的分子因子可能影响乳腺癌对化疗的反应。在此，我们研究了核因子κ B (nf - κ B)/bcl-2途径，以确定该抗凋亡途径的激活是否与人类乳腺癌对蒽环类新辅助化疗的不良反应有关。实验设计：我们研究了82例接受新辅助多柔比星化疗的人乳腺癌样本，研究转录因子NF-kappa B的核位置是否与bcl-2和bax的表达相关，以及这些蛋白的表达是否与化疗反应相关。免疫组化染色检测蛋白表达。一位不知道临床结果数据的专门的乳腺癌病理学家根据是否存在bcl-2和bax的细胞质染色或NF-kappa b的核染色，将载玻片分为阳性或阴性。bcl-2阳性的肿瘤61%，bax阳性的肿瘤85%，NF-kappa b阳性的肿瘤16%，bcl-2阳性的肿瘤同时bax阳性（P < 0.0001）， NF-kappa b阳性的肿瘤同时bcl-2阳性（P = 0.001）和bax阳性（P = 0.113）。82例患者中有11例（13%）对化疗有病理完全缓解（pCR）。与肿瘤染色阴性的患者相比，肿瘤染色阳性的患者对化疗的pCR反应较少。NF-kappa B阳性率为0%（13例中0例），KF-kappa B阴性率为13%(69例中11例，P = 0.130)；bcl-2阳性4%（49人中2人）vs bcl-2阴性27%(33人中9人；P = 0.004)；bax阳性6%（69人中4人），bax阴性58%（12人中7人；P < 0.001）。结论：我们认为NF-kappa B的核定位与bcl-2和bax的表达有关，NF-kappa B/bcl-2通路可能与新辅助阿霉素化疗的不良反应有关。
Purpose: Molecular factors involved in apoptosis may affect breast cancer response to chemotherapy. Herein, we studied the nuclear factor kappa B (NF-kappa B)/bcl-2 pathway to determine whether or not activation of this antiapoptotic pathway was associated with a poor response of human breast cancer to anthracycline-based neoadjuvant chemotherapy.Experimental Design: We studied 82 human breast cancer samples from patients treated with neoadjuvant doxorubicin-based chemotherapy and studied whether or not nuclear location of the transcription factor NF-kappa B was associated with expression of bcl-2 and bax and whether or not expression of these proteins correlated with chemotherapy response. Protein expression was measured with immunohistochemical staining. A dedicated breast cancer pathologist who was unaware of the clinical outcome data dichotomized the slides as positive or negative based on the presence or absence of cytoplasmic staining for bcl-2 and bax or nuclear staining for NF-kappa B.Results: Sixty-one percent of the tumors were positive for bcl-2, 85% were positive for bax, and 16% were positive for NF-kappa B. All bcl-2-positive tumors were also bax positive (P < 0.0001) and all NF-kappa B-positive tumors were both bcl-2 positive (P = 0.001) and bax positive (P = 0.113). Eleven of the 82 patients (13%) had a pathologic complete response (pCR) to chemotherapy. Patients with positive staining tumors for any of the markers less commonly achieved a pCR to chemotherapy than those with negative tumor staining. The pCR rates were NF-kappa B positive 0% (0 of 13) versus KF-kappa B negative 13% (11 of 69; P = 0.130); bcl-2 positive 4% (2 of 49) versus bcl-2 negative 27% (9 of 33; P = 0.004); and bax positive 6% (4 of 69) versus bax negative 58% (7 of 12; P < 0.001).Conclusion: We conclude that nuclear localization of NF-kappa B correlates with bcl-2 and bax expression and that the NF-kappa B/bcl-2 pathway may be associated with a poor response to neoadjuvant doxorubicin-based chemotherapy.