GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.
GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.
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DOI：
10.1007/s10549-009-0631-7
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发表时间：
2010-08
影响因子：
3.8
通讯作者：
Cristofanilli, Massimo
中科院分区：
文献类型：
--
作者：
Arias-Pulido, Hugo;Royce, Melanie;Gong, Yun;Joste, Nancy;Lomo, Lesley;Lee, Sang-Joon;Chaher, Nabila;Verschraegen, Claire;Lara, Juanita;Prossnitz, Eric R.;Cristofanilli, Massimo
关键词：
GPR30是一种新型G蛋白偶联的雌激素受体（ER），与乳腺癌中的转移（BC）相关，子宫内膜和卵巢肿瘤的存活率差。尚未研究GPR30表达与炎症性乳腺癌（IBC）的关联，这是BC的侵略性且通常是激素独立的形式。
在88个原发性IBC中，通过免疫组织化学（HER-2）评估了GPR30，ER，孕酮受体（PR），表皮生长因子受体（EGFR）和HER-2表达。 GPR30表达与患者总生存期（OS），无疾病生存（DFS），病理变量和其他生物标志物相关。
在69％的IBC病例中发现了GPR30表达。 ER，PR，HER-2和EGFR分别在43％，35％，39％和34％的IBC病例中发现。 GPR30表达与ER表达相关（P = 0.02）。在24％的IBC样品中发现了ER和GPR30的共表达； 19％的人只表示ER，46％的人仅表示GPR30。单变量分析显示GPR30表达与OS或DF之间没有关联。然而，ER和GPR30的共表达与改善OS（P <0.03）有关，并且与DFS略微相关（P <0.06）； ER和GPR30的不存在与OS和DF较差有关（两者p = 0.03）。多变量分析将ER确定为OS的独立预后因素（P = 0.008）和DFS（P = 0.02）。
大多数IBC肿瘤是GPR30阳性的，这表明雌激素信号在ER阴性IBC患者中可能活跃。这些发现表明了IBC的潜在新治疗靶标，例如新型内分泌药物或GPR30的直接调节。
GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR) and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2 and EGFR were found in 43%, 35%, 39%, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P=0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P<0.03) and marginally with DFS (P<0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P=0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P=0.008) and DFS (P=0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.
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