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基因组守护者蛋白质表达对三阴性 乳腺癌化疗效果和生存结局的影响 TP53基因编码分子质量为53kDa的蛋白质而得名，属于抑癌基因（肿瘤抑制基因）之一，其表达产物P53蛋白为基因调节蛋白，当DNA受到损伤时表达产物急剧增加，可抑制细胞周期进一步运转。一旦TP53基因发生突变，P53蛋白失活，细胞分裂失去节制，发生癌变，人类癌症中约有一半是由于该基因发生突变失活。因此，P53被称为基因组守护者。TP53突变是乳腺癌最常见的突变，尤其三阴性乳腺癌。由于TP53突变后表达的突变型P53蛋白比野生型P53蛋白稳定，故可被免疫化学染色检出。 2018年8月21日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表高丽大学安岩医院、成均馆大学三星首尔医院、亚洲大学医学院、蔚山大学首尔峨山医院、延世大学医学院、梨花女子大学木洞医院、国立全北大学医院的大数据研究报告，探讨了通过免疫化学染色检出的P53蛋白表达水平能否预测三阴性乳腺癌化疗效果。 该研究对韩国乳腺癌学会登记数据库2000年1月1日～2015年12月31日共计1万1393例I～III期三阴性乳腺癌患者进行分析，其中P53阳性6331例、P53阴性5062例。 结果发现，根据单因素分析，P53阳性与阴性相比，未接受化疗患者的总生存结局较差（P=0.003），接受化疗患者的总生存结局相似。 根据针对年龄和分期校正的多因素分析，P53阳性与阴性相比，未化疗组患者的死亡风险高84%（风险比：1.84，95%置信区间：1.070～3.162），化疗组患者的死亡风险相似（风险比：1.005，95%置信区间：0.847～1.192）。 化疗与未化疗相比，P53阳性患者的死亡风险低39.9%（风险比：0.611，95%置信区间：0.418～0.891），P53阴性患者的死亡风险相似（风险比：0.879，95%置信区间：0.504～1.533）。 因此，根据该研究结果，P53阳性与阴性相比，三阴性乳腺癌的生存结局较差，但是化疗可以显著减少死亡风险，表明P53阳性三阴性乳腺癌对化疗的敏感性较高。 Breast Cancer Res Treat. 2018 Aug 21. Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer. Soo Youn Bae, Seok Jin Nam, Yongsik Jung, Sae Byul Lee, Byung-Woo Park, Woosung Lim, Sung Hoo Jung, Hsien Wen Yang, Seung Pil Jung. Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Ajou University School of Medicine, Gyeonggi-do, Korea; Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Yonsei University College of Medicine, Seoul, Korea; Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea; Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea. PURPOSE: TP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple-negative breast cancer (TNBC). We investigated whether expression of p53 detected by immunochemical staining predicts the chemotherapy response of TNBC. METHODS: A total of 11,393 TNBC patients who had between stage I and stage III enrolled in the Korean Breast Cancer Society Registry database from January 1, 2000 to December 31, 2015. There were 6,331 'p53-positive (+) TNBC' patients and 5062 'p53-negative (-) TNBC' patients. RESULTS: In univariate analysis, p53(+) TNBC had a worse prognosis than p53(-) TNBC in patients not receiving chemotherapy (P=0.003). However, there was no difference in prognosis between p53(+) TNBC and p53(-) TNBC for patients receiving chemotherapy. In multivariate analysis adjusted for age and stage, the risk of p53(+) TNBC was 1.84 times higher than that of p53(-) TNBC in the non-chemotherapy group. However, there was no difference between p53(+) TNBC and p53(-) TNBC in patients receiving chemotherapy. In p53(+) TNBC, the risk was 0.6-fold lower when chemotherapy was administered than when chemotherapy was not administered. However, in p53(-) TNBC, there was no risk reduction effect by chemotherapy. CONCLUSION: The prognosis of p53(+) TNBC has worse than p53(-) TNBC, but the risk for survival was significantly reduced with chemotherapy. It suggests that p53(+) TNBC would be more sensitive to chemotherapy than p53(-) TNBC. KEYWORDS: Triple-negative breast cancer Chemotherapy Prognosis P53 Immunohistochemistry DOI: 10.1007/s10549-018-4928-2
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