Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.
Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.
复制标题
激素受体表达和卵巢癌存活：卵巢肿瘤组织分析联盟研究。
DOI：
10.1016/s1470-2045(13)70253-5
复制
发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Ramus SJ
中科院分区：
文献类型：
--
作者：
Sieh W;Köbel M;Longacre TA;Bowtell DD;deFazio A;Goodman MT;Høgdall E;Deen S;Wentzensen N;Moysich KB;Brenton JD;Clarke BA;Menon U;Gilks CB;Kim A;Madore J;Fereday S;George J;Galletta L;Lurie G;Wilkens LR;Carney ME;Thompson PJ;Matsuno RK;Kjær SK;Jensen A;Høgdall C;Kalli KR;Fridley BL;Keeney GL;Vierkant RA;Cunningham JM;Brinton LA;Yang HP;Sherman ME;García-Closas M;Lissowska J;Odunsi K;Morrison C;Lele S;Bshara W;Sucheston L;Jimenez-Linan M;Driver K;Alsop J;Mack M;McGuire V;Rothstein JH;Rosen BP;Bernardini MQ;Mackay H;Oza A;Wozniak EL;Benjamin E;Gentry-Maharaj A;Gayther SA;Tinker AV;Prentice LM;Chow C;Anglesio MS;Johnatty SE;Chenevix-Trench G;Whittemore AS;Pharoah PD;Goode EL;Huntsman DG;Ramus SJ
卵巢癌是一种由不同的组织病理学类型组成的致命疾病。卵巢癌预后的生物标志物很少，部分原因是在结合所有亚型的研究中，亚型特异性关联可能被掩盖了。在国际卵巢肿瘤组织分析(OTTA)联盟中，我们研究了孕激素受体(PR)和雌激素受体(ER)蛋白的表达是否与亚型特异性生存有关。对12个研究点的2933例浸润性上皮性卵巢癌患者进行了组织芯片中心免疫组织化学分析，以检测PR和ER。阴性、弱和强表达分别定义为1%、1-50%和≥50%的肿瘤细胞核呈阳性表达。卵巢癌死亡的风险比(HR)是用COX回归估计的，按部位分层，并根据年龄、分期和级别进行调整。PR的表达与子宫内膜样癌(EC；p<；0·0001)和高级别浆液性癌(HGSC；p=0·0006)生存率的改善有关，ER的表达与EC生存率的改善(p<；0·0001)相关；与粘液性、透明细胞或低级别浆液性癌无关。激素受体(PR和/或ER)阳性(弱或强)的EC患者死于疾病的风险显著降低，与临床因素无关(HR，0.33；95%CI，0.21~0.51；P<；0.0001)。肿瘤PR表达强与弱或阴性相比，HGSC患者死于疾病的风险显著降低，与临床因素无关(HR，0.71；95%CI，0.55-0.91；p=0.0061)。PR和ER是子宫内膜样癌和高级别浆液性卵巢癌的预后生物标志物。需要按亚型和生物标志物状态分层的临床试验，以确定激素受体状态是否可以预测内分泌治疗的反应，并可以指导卵巢癌的个性化治疗。Carraressi基金会、美国国立卫生研究院、澳大利亚国家卫生和医学研究委员会、英国国家卫生研究所等。
Ovarian cancer is a lethal disease comprised of distinct histopathological types. There are few established biomarkers of ovarian cancer prognosis, in part because subtype-specific associations may have been obscured in studies combining all subtypes. We examined whether progesterone receptor (PR) and estrogen receptor (ER) protein expression were associated with subtype-specific survival in the international Ovarian Tumor Tissue Analysis (OTTA) consortium. PR and ER were assessed by central immunohistochemical analysis of tissue microarrays for 2933 women with invasive epithelial ovarian cancer from 12 study sites. Negative, weak, and strong expression were defined as positive staining in <1%, 1–50%, and ≥50% of tumor cell nuclei, respectively. Hazard ratios (HRs) for ovarian cancer death were estimated using Cox regression stratified by site and adjusted for age, stage, and grade. PR expression was associated with improved survival for endometrioid (EC; p<0·0001) and high-grade serous carcinoma (HGSC; p=0·0006), and ER expression was associated with improved EC survival (p<0·0001); no significant associations were found for mucinous, clear cell, or low-grade serous carcinoma. EC patients with hormone receptor (PR and/or ER) positive (weak or strong) versus negative tumors had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·33; 95% CI, 0·21–0·51; p<0·0001). HGSC patients with strong versus weak or negative tumor PR expression had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·71; 95% CI, 0·55–0·91; p=0·0061). PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to determine whether hormone receptor status predicts response to endocrine therapy, and can guide personalized treatment for ovarian cancer. Carraressi Foundation, US National Institutes of Health, National Health and Medical Research Council of Australia, UK National Institute for Health Research, and others.