Colorectal Tumor Nucleus of the Pelvic Surgery Department, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
Colorectal Tumor Nucleus of the A.C. Camargo Cancer Center, R. Professor Antônio Prudente, 211 Liberdade, São Paulo, São Paulo, SP, CEP 01509-010, Brazil.
BMC Cancer. 2017 Nov 13;17(1):754. doi: 10.1186/s12885-017-3688-4.
Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described.
This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas.
Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERβ1 and ERβ5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002).
These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.
在性激素中，雌激素可能在结直肠癌中发挥作用，尤其是与雌激素受体-β（ERβ）结合时。ERβ 同工型变体的表达及其与家族性腺瘤性息肉病（FAP）综合征和散发性结直肠癌的相关性描述甚少。
本研究旨在使用定量 RT-PCR（921 次分析）检测 ERβ1、ERβ2、ERβ4 和 ERβ5 同工型变体在 FAP、正常黏膜、腺瘤性息肉和散发性结直肠癌中的表达水平。
与正常组织相比，散发性息肉和散发性结直肠癌以及 FAP 综合征患者的息肉中 ERβ 同工型表达降低（p<0.001）。在 FAP 患者中，与匹配的正常组织相比，ERβ1 和 ERβ5 同工型在息肉中表现出明显的下调（p<0.001）。然而，当将散发性结直肠癌与正常黏膜组织进行比较时，并未观察到差异。这些发现提示 ERβ 同工型变体与 APC 基因突变的个体有关。在低级别异型增生早期阶段的息肉中发现 ERβ 的表达逐渐降低，随后是 T1-T2 和 T3-T4 肿瘤（p<0.05）。在散发性结直肠癌中，表达缺失是复发的独立预测因素，ERβ1 和 ERβ5 的表达水平与更好的无病生存率相关（p=0.002）。
这些发现可能有助于更好地了解雌激素及其对散发性结直肠癌和与 FAP 综合征相关癌症的潜在预防和治疗作用。
