Osanai Makoto, Lee Gang-Hong
Department of Pathology, Kochi University School of Medicine, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Med Mol Morphol. 2016 Mar;49(1):22-7. doi: 10.1007/s00795-015-0110-7. Epub 2015 May 26.
Retinoic acid (RA)-metabolizing enzyme CYP26A1 has been shown to have increased expression levels in breast cancers and to effectively promote the survival of breast carcinoma cells, implying a potential oncogenic function. However, the expression of CYP26C1, another CYP26 family member, in primary breast carcinoma remains to be clarified. In the present study, we examined the expression of CYP26C1 by immunohistochemistry, using three different types of microarray, and observed strong cytoplasmic staining of CYP26C1 in 73 of the 219 (33.3 %) breast carcinomas. In contrast, CYP26C1 was not expressed in normal ductal and lobular cells in non-neoplastic tissue. Interestingly, increased expression of CYP26C1 was significantly associated with a high Ki-67 labeling index and a grade of tumor. However, CYP26C1 immunoreactivity was not associated with clinicopathological variables, including primary tumor status, lymph node involvement, distant metastasis, and tumor stage. In addition, CYP26C1 positivity was independent of the expression status of the hormone receptors and immunohistochemical surrogates for the intrinsic subtypes of breast cancer. This report is the first to demonstrate elevated expression of CYP26C1 in primary breast carcinomas. Based on the RA-catabolizing activity of CYP26C1, our data suggest that CYP26C1 expression may contribute to neoplasia in the breast.
维甲酸(RA)代谢酶CYP26A1已被证明在乳腺癌中表达水平升高,并能有效促进乳腺癌细胞的存活,这意味着它具有潜在的致癌功能。然而,另一个CYP26家族成员CYP26C1在原发性乳腺癌中的表达仍有待阐明。在本研究中,我们通过免疫组织化学,使用三种不同类型的微阵列检测了CYP26C1的表达,并在219例乳腺癌中的73例(33.3%)中观察到CYP26C1的强细胞质染色。相比之下,CYP26C1在非肿瘤组织的正常导管和小叶细胞中不表达。有趣的是,CYP26C1表达增加与高Ki-67标记指数和肿瘤分级显著相关。然而,CYP26C1免疫反应性与临床病理变量无关,包括原发性肿瘤状态、淋巴结受累、远处转移和肿瘤分期。此外,CYP26C1阳性与激素受体的表达状态以及乳腺癌内在亚型的免疫组化替代指标无关。本报告首次证明CYP26C1在原发性乳腺癌中表达升高。基于CYP26C1的RA分解代谢活性,我们的数据表明CYP26C1表达可能促成乳腺肿瘤形成。