Yamashita Hiroko, Nishio Mariko, Toyama Tatsuya, Sugiura Hiroshi, Kondo Naoto, Kobayashi Shunzo, Fujii Yoshitaka, Iwase Hirotaka
Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Endocr Relat Cancer. 2008 Sep;15(3):755-63. doi: 10.1677/ERC-08-0078. Epub 2008 Jun 12.
Endocrine therapy has become the most important treatment option for women with estrogen receptor (ER)-positive breast cancer. Urgently needed are prognostic assays that can identify those who need additional adjuvant therapy, such as signal transduction inhibitors or chemotherapy, for ER-positive early breast cancer. We examined phosphorylation of ERalpha serine (Ser) 118, ERalpha Ser167, p44/42 mitogen-activated protein kinase (MAPK), and Akt and expression of progesterone receptor, amplified in breast cancer 1 (AIB1), human epidermal growth factor receptor 2 (HER2), p53, and Ki67 in ER-positive breast cancers by immunohistochemistry, and analyzed their significance for prognosis. Phosphorylation levels of ERalpha Ser118, ERalpha Ser167, MAPK, and Akt were positively correlated. AIB1 expression was significantly associated with phosphorylation of ERalpha Ser118, MAPK, and Akt, and HER2 expression. Low phosphorylation of ERalpha Ser118 and high phosphorylation of ERalpha Ser167 were associated with significantly improved disease-free (P=0.0003 and P=0.0002 respectively) and overall survival (P=0.0007 and P=0.0016 respectively) in multivariate analyses. Our data suggest that phosphorylation of ERalpha Ser118 and ERalpha Ser167 affects survival in ER-positive breast cancer and could be helpful in distinguishing patients who are likely to benefit from endocrine therapy alone from those who are not.
内分泌治疗已成为雌激素受体（ER）阳性乳腺癌女性最重要的治疗选择。对于ER阳性早期乳腺癌，迫切需要能够识别那些需要额外辅助治疗（如信号转导抑制剂或化疗）的患者的预后检测方法。我们通过免疫组织化学检测了ERα丝氨酸（Ser）118、ERα Ser167、p44/42丝裂原活化蛋白激酶（MAPK）和Akt的磷酸化，以及ER阳性乳腺癌中孕激素受体、乳腺癌1（AIB1）扩增、人表皮生长因子受体2（HER2）、p53和Ki67的表达，并分析了它们对预后的意义。ERα Ser118、ERα Ser167、MAPK和Akt的磷酸化水平呈正相关。AIB1表达与ERα Ser118、MAPK和Akt的磷酸化以及HER2表达显著相关。在多因素分析中，ERα Ser118低磷酸化和ERα Ser167高磷酸化分别与无病生存期（分别为P = 0.0003和P = 0.0002）和总生存期（分别为P = 0.0007和P = 0.0016）的显著改善相关。我们的数据表明，ERα Ser118和ERα Ser167的磷酸化影响ER阳性乳腺癌的生存，并且有助于区分可能仅从内分泌治疗中获益的患者和不能获益的患者。
