ERβ expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis

ERβ expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis
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DOI:
10.3109/00365521.2010.487915
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发表时间:
2010-11-01
影响因子:
1.9
通讯作者:
Di Leo, Alfredo
Di Leo, Alfredo
中科院分区:
医学4区
文献类型:
--
作者:
Barone, Michele;Scavo, Maria Principia;Di Leo, Alfredo

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目标. APC基因突变引发家族性腺瘤性息肉病(FAP)和大约80%的散发性结直肠癌。FAP总结了结直肠癌的自然史,因为低级别和高级别异型增生病变和腺癌同时存在于同一患者中,不受个体和环境变异因素的影响。雌激素受体β(ER β)最近被认为是Apc(Min-/+)小鼠和人类中雌激素相关抗癌作用的最可能介质。在这项研究中,我们评估了FAP患者肠粘膜中ER β的表达,以验证其可能参与结直肠癌的肿瘤进展。材料和方法。ER β和ER α表达,细胞增殖(Ki-67)和凋亡(TUNEL),从6例接受结肠切除术的FAP患者的存档活检材料进行了评价。结果与正常粘膜相比,在疾病的不同阶段观察到ER β表达进行性显著降低(p < 0.001)。有趣的是,ER β表达降低与细胞凋亡直接相关(r = 0.76,p < 0.001),与细胞增殖负相关(r = 0.54,p < 0.05)。结论. ER β表达与疾病的严重程度相关,支持ER β作为肿瘤进展的相关生物标志物和结肠肿瘤风险患者中可能的化学预防靶点的作用。
Objectives. The APC gene mutation triggers familial adenomatous polyposis (FAP) and approximately 80% of sporadic colorectal cancers. FAP summarizes the natural history of colorectal cancer because low-and high-grade dysplastic lesions and adenocarcinoma are simultaneously present in the same patients free from individual and environmental variability factors. Estrogen receptor beta (ER beta) has recently been suggested as the most likely mediator of estrogen-related anti-carcinogenic effects in Apc(Min-/+) mice and humans. In this study we assessed the ER beta expression in the intestinal mucosa of FAP patients to verify its possible involvement in tumor progression in colorectal cancer. Material and methods. ER beta and ER alpha expression, cell proliferation (Ki-67) and apoptosis (TUNEL), were evaluated on archival biopsy material from six patients with FAP who underwent colectomy. Results. A progressive significant decrease of ER beta expression was observed in the different stages of the disease as compared to normal mucosa (p < 0.001). Interestingly, a decreased ER beta expression was directly correlated with apoptosis (r = 0.76, p < 0.001), and inversely correlated with cell proliferation (r = 0.54, p < 0.05). Conclusions. ER beta expression is related to the severity of the disease, supporting the role of ER beta as a relevant biomarker of tumor progression and possible chemopreventive target in patients at risk of colonic neoplasia.