Ariga N, Moriya T, Suzuki T, Kimura M, Ohuchi N, Sasano H
Department of Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai 980-8575, Japan.
Jpn J Cancer Res. 2000 Nov;91(11):1169-76. doi: 10.1111/j.1349-7006.2000.tb00901.x.
Retinoic acid (RAR) and retinoid X receptors (RXR) are essential in the transcriptional actions of retinoids. To date, RAR and RXR have not been examined in precancerous lesions and / or ductal carcinoma in situ (DCIS) in human breast. Therefore, we examined RAR and RXR subtypes in DCIS (58 cases), atypical ductal hyperplasia (ADH) (32 cases), and proliferative disease without atypia (PDWA) (32 cases) to study the status of these RARs and RXRs. Immunoreactivities for RAR alpha, RXR alpha, RXR beta, and RXR gamma were all detected in the nuclei of normal ductal epithelia. Immunoreactivity for RAR beta was detected exclusively in the nuclei of myoepithelial cells, but not in normal ductal epithelia. Immunoreactivity for RAR gamma was not detected in any of the breast tissues examined except for a few cases of PDWA and ADH, and 11 cases of DCIS. The RXR alpha labeling index (LI) was significantly higher in both DCIS (mean 77.9) and ADH (mean 77.7) than in PDWA (mean 62.8) (P < 0.001). RXR beta LI was significantly lower in DCIS (mean 81.5) than in both ADH (mean 91.1) and PDWA (mean 91.9) (P = 0.0001). Immunoreactivity for RAR alpha, RXR alpha, RXR beta and RXR gamma was widely distributed compared to that of RAR beta and RAR gamma in DCIS, ADH and PDWA. RAR alpha LI was significantly correlated with Ki67 LI in DCIS (P = 0.0040), especially in estrogen receptor (ER)-positive DCIS. Our results suggest that RXRs are much more widely distributed than RARs in intraductal proliferative lesions of tne human breast, but ER-positive DCIS cases with high cell proliferative activity are associated with RAR alpha, suggesting the possible involvement of retinoids through RAR alpha in tumor cell proliferation in DCIS.
维甲酸（RAR）和维甲酸X受体（RXR）在类视黄醇的转录作用中至关重要。迄今为止，尚未在人乳腺的癌前病变和/或导管原位癌（DCIS）中检测过RAR和RXR。因此，我们检测了DCIS（58例）、非典型导管增生（ADH）（32例）和无异型增生性疾病（PDWA）（32例）中的RAR和RXR亚型，以研究这些RAR和RXR的状态。在正常导管上皮细胞核中均检测到RARα、RXRα、RXRβ和RXRγ的免疫反应性。RARβ的免疫反应性仅在肌上皮细胞核中检测到，而在正常导管上皮细胞中未检测到。除少数PDWA和ADH病例以及11例DCIS外，在所检查的任何乳腺组织中均未检测到RARγ的免疫反应性。DCIS（平均77.9）和ADH（平均77.7）中的RXRα标记指数（LI）均显著高于PDWA（平均62.8）（P<0.001）。DCIS（平均81.5）中的RXRβ LI显著低于ADH（平均91.1）和PDWA（平均91.9）（P = 0.0001）。与DCIS、ADH和PDWA中的RARβ和RARγ相比，RARα、RXRα、RXRβ和RXRγ的免疫反应性分布更广泛。DCIS中RARα LI与Ki67 LI显著相关（P = 0.0040），尤其是在雌激素受体（ER）阳性的DCIS中。我们的结果表明，在人乳腺导管内增生性病变中，RXRs的分布比RARs广泛得多，但具有高细胞增殖活性的ER阳性DCIS病例与RARα相关，提示类视黄醇可能通过RARα参与DCIS中的肿瘤细胞增殖。
