Høgdall Estrid V S, Christensen Lise, Høgdall Claus K, Blaakaer Jan, Gayther Simon, Jacobs Ian J, Christensen Ib Jarle, Kjaer Susanne K
Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Oncol Rep. 2007 Nov;18(5):1051-9.
Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR, alone and in combination, point to a favorable outcome for patients with OC.
雌激素和孕激素是卵巢分泌的重要激素，通过特定受体发挥作用。这些激素在肿瘤组织中的表达谱已在乳腺癌、子宫癌和前列腺癌等恶性肿瘤中显示出预后价值。在本研究中，我们纳入了773例丹麦卵巢肿瘤患者的组织样本，评估雌激素受体（ER）和孕激素受体（PR）表达是否与临床病理参数相关，并研究其对卵巢癌（OC）患者可能的预后影响。我们使用组织芯片和免疫组织化学方法，分析了582例OC患者和191例低恶性潜能（LMP）卵巢肿瘤患者组织中的ER和PR表达水平。我们的结果表明，191例LMP肿瘤中有30例（16%）表达ER，582例OC中有207例（36%）表达ER。38例LMP肿瘤（20%）和115例OC（20%）表达PR。与黏液性亚型相比，两种肿瘤类型的浆液性亚型中阳性肿瘤均更多（p≤0.00001）。ER表达阳性的OC频率随国际妇产科联盟（FIGO）分期增加而升高（p = 0.0003），PR阳性肿瘤频率随组织学分级增加而升高（p = 0.0006）。在Cox生存分析中，发现组织ER和PR表达≥10%意味着患者疾病特异性生存有独立的显著有利进程（ER：风险比（HR），0.80；95%置信区间（CI），0.63 - 0.99；PR：HR，0.69；95% CI，0.51 - 0.94），同时与FIGO分期、初次手术后残留肿瘤、诊断时年龄以及其他组织学类型与浆液性腺癌相比有关。发现肿瘤的组织学分级无独立预后价值。与两种受体表达均<10%的患者相比，ER和PR高表达患者的HR为0.48（95% CI，0.31 - 0.74），发现ER和PR的预后价值具有相加性。总之，我们的结果预测，ER和PR单独或联合表达升高表明OC患者预后良好。
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