Ferrandina Gabriella, Ranelletti Franco Oreste, Gallotta Valerio, Martinelli Enrica, Zannoni Gian Franco, Gessi Marco, Scambia Giovanni
Gynecologic Oncology Unit, Catholic University of Rome, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy.
Gynecol Oncol. 2005 Sep;98(3):383-9. doi: 10.1016/j.ygyno.2005.04.024.
We aimed at investigating by immunohistochemistry the relationship between cyclooxygenase-2 (COX-2) and estrogen (ER), and progesterone (PR) receptors in a single institution series of 90 primary untreated endometrial cancer patients. The simultaneous assessment of p53 protein, ki67, and neu protein has been carried out.
Immunohistochemistry was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against human COX-2, anti-ER (clone 1D5), and anti-PR (clone 1A6) monoclonal antibodies, anti ki67 (clone MIB-1) and p53 (clone DO-7), and polyclonal antibody anti human c-erbB2/neu.
There was no difference in the distribution of COX-2, p53, and neu positive cases according to ER or PR positivity, while the percentage of ki67 positive endometrial tumors was significantly higher in ER negative versus ER positive tumors (54.5% versus 31.6%, P value = 0.044). ER and PR positive tumors showed a statistically significant association with clinicopathological parameters of better clinical outcome. There was no clear association between COX-2 positivity and any of the clinicopathological features. The percentage of ki67, p53, and neu positive tumors was found to be strictly related to more aggressive features. Only advanced stage of disease was found to be a predictor of poor prognosis (P value = 0.034). None of the biological parameters examined was shown to be associated with patient outcome.
We showed that COX-2 expression is not correlated with ER, PR, p53, and neu, thus suggesting that COX-2-mediated activities may follow independent pathways. Our findings provide the rationale to design trials based on the combination of antihormones with inhibitors of COX-2 and neu in recurrent/metastatic endometrial cancer.
我们旨在通过免疫组织化学方法，研究在一家机构的90例未经治疗的原发性子宫内膜癌患者系列中，环氧化酶-2（COX-2）与雌激素（ER）及孕激素（PR）受体之间的关系。同时对p53蛋白、ki67和neu蛋白进行了评估。
采用兔抗人COX-2多克隆抗血清、抗ER（克隆1D5）和抗PR（克隆1A6）单克隆抗体、抗ki67（克隆MIB-1）和p53（克隆DO-7）以及抗人c-erbB2/neu多克隆抗体，对石蜡包埋切片进行免疫组织化学检测。
根据ER或PR的阳性情况，COX-2、p53和neu阳性病例的分布没有差异，而ER阴性的子宫内膜肿瘤中ki67阳性的百分比显著高于ER阳性肿瘤（54.5%对31.6%，P值=0.044）。ER和PR阳性肿瘤与临床结局较好的临床病理参数存在统计学上的显著关联。COX-2阳性与任何临床病理特征之间没有明显关联。发现ki67、p53和neu阳性肿瘤的百分比与更具侵袭性的特征密切相关。仅疾病晚期被发现是预后不良的预测因素（P值=0.034）。所检测的生物学参数均未显示与患者结局相关。
我们表明COX-2表达与ER、PR、p53和neu无关，因此提示COX-2介导的活性可能遵循独立途径。我们的研究结果为设计基于抗激素与COX-2和neu抑制剂联合应用于复发性/转移性子宫内膜癌的试验提供了理论依据。
