目的:检测视黄酸受体β2(RAR—β2)基因在不同乳腺肿瘤组织中的表达,探讨RAR-β2基因与乳腺肿瘤的关系,分析其在乳腺癌发生、发展中的作用。方法:免疫组织化学法检测乳腺浸润性癌、导管上皮重度不典型增生、腺纤维瘤各40例及20例正常乳腺组织中RAR-β2的表达情况。RT—PCR法检测乳腺浸润性癌、导管上皮重度不典型增生、腺纤维瘤及正常乳腺组织各20例RAR-β2的表达水平。结果:免疫组化结果显示。RAR-β2阳性表达主要位于细胞核,RAR-β2蛋白在乳腺浸润癌组织中阳性表达率(30.0%)明显低于正常乳腺组织(95.0%),Χ^2=26.30,P〈0.05。RAR-β2蛋白在乳腺重度不典型增生组织中阳性表达率(17.5%)低于乳腺癌组织,但差异无统计学意义(P〉0.05)。在乳腺浸润性癌组织中,RAR-β2表达与患者年龄、肿瘤大小、临床分期、腋下淋巴结转移状况、组织学分级、病理学类型以及ER、PR表达状况无相关性(P均〉0.05)。随访结果显示,28例RAR-β2阴性乳腺癌患者中3例发生内脏转移,而12例RAR-β2阳性患者仅1例发生骨转移。RT—PCR结果显示,RAR-β2在乳腺癌、导管上皮重度不典型增生、腺纤维瘤及正常乳腺组织中阳性表达率分别为25.0%(5/20)、35.0%(7/20)、85.0%(17,20)和100%(20/20),乳腺癌组织RAR-β2mRNA明显低于正常乳腺组织(Χ^2=30.43,P〈0.001)。结论:RAR-β2可能在乳腺癌的发生过程中发挥抑制作用,并且可能在乳腺癌发生的早期发挥作用。
Objective: To assess the expression of retinoic acid receptor beta 2 (RAR-β2) in breast tumor and to evaluate the relationship between RAR-β2 expression and tumorigenesis of breast cancer. Methods: Immunohistochemistry was used to detect the expression of RAR-β2 protein in specimens from 40 cases of breast cancer, 40 cases of atypical ductal hyperplasia, 40 cases of fibroadenoma and 20 cases of normal breast tissues. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of RAR-β2 gene in 20 cases of breast cancer, 20 cases of atypical ductal hyperplasia, 20 cases of fibroadenoma, and 20 cases of normal breast tissues. Results: Immunohistochemical staining results revealed that the positive expression of RAR-β2 protein showed nuclear staining. The positive expression rate of RAR-β2 was 30% (12/40) in breast cancer, 17.5% (7/40) in atypical ductal hyperplasia, 87.5% (35/40) in fibroadenoma, and 95% (19/20) in normal breast tissues. The expression of RAR-β2 protein in breast cancer was significantly lower than that in normal breast tissues (Χ^2=26.30, P〈0.001). The expression of RAR-β2 was not significantly different between atypical ductal hyperplasia and breast cancer (P〉0.05). No correlation was found between the expression of RAR-β 2 protein and the tumor size, menopausal age, lymph node metastasis, clinical stage, histological grade, or protein expression of ER and PR in breast cancer tissues (P)〉0.05). Follow-up results showed that 3 out of 28 patients with negative RAR-β2 expression had visceral organ metastasis, but only one of the 12 RAR-β2 positive patients had osseous metastasis. RT-PCR analysis showed that the positive expression rate of RAR-β2 mRNA in breast cancer, atypical ductal hyperplasia, fibroadenoma and normal breast tissues was 25% (5/20), 35% (7/20), 85% (17/20) and 100% (20/20), respectively. The RAR-β2 mRNA expression rate in breast cancer was significantly lower t