Katsetos C D, Stadnicka I, Boyd J C, Ehya H, Zheng S, Soprano C M, Cooper H S, Patchefsky A S, Soprano D R, Soprano K J
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Am J Pathol. 1998 Aug;153(2):469-80. doi: 10.1016/s0002-9440(10)65590-3.
Retinoids are effective growth modulators of human ovarian carcinoma cell lines. Their effects are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are transcriptional factors and members of the steroid/thyroid receptor superfamily. To our knowledge, until now, the cellular distribution of RAR proteins in human ovarian tumor specimens is unknown. This study provides new data on the differential cellular localization of RAR alpha protein in 16 serous adenocarcinomas originating from the ovaries, fallopian tubes, and the peritoneum. Using an affinity-purified antiserum specific for RAR alpha and a monoclonal antibody recognizing the full-length estrogen receptor molecule (clone 6F11), we performed immunohistochemistry on frozen tissue sections and examined the relationship between RAR alpha and estrogen receptor protein expression by comparing the percentage of immunostained tumor cells for either receptor. Our findings indicate a strong linear relationship between the percentages of RAR alpha- and estrogen receptor-labeled tumor cells as determined by linear regression analysis (P < 0.005, r = 0.825). A modest inverse relationship was found between the percentage of RAR alpha-positive tumor cells and histological grade, attesting to a differentiation-dependent trend (P < 0.04). No significant relationship was found between RAR alpha-labeled cells and clinical stage (P = 0.139), site of tumor origin (ovaries versus fallopian tubes versus peritoneum) (P = 0.170), and primary versus metastatic lesion (P = 0.561). Thus, serous adenocarcinomas are capable of expressing RAR alpha and estrogen receptor despite high histological grade and advanced stage of neoplastic disease. Compared with the heterogeneous localization of RAR alpha in cancer cells, there was widespread RAR alpha immunoreactivity in tumor-infiltrating lymphocytes, vascular endothelial cells, and stromal fibroblasts, underscoring the value of immunohistochemistry in the accurate determination of RAR/(RXR) content in tumor specimens.
维甲酸是人类卵巢癌细胞系有效的生长调节剂。它们的作用由核视黄酸受体（RARs）和视黄酸X受体（RXRs）介导，这些受体是转录因子，属于类固醇/甲状腺受体超家族成员。据我们所知，到目前为止，人类卵巢肿瘤标本中RAR蛋白的细胞分布尚不清楚。本研究提供了有关16例源自卵巢、输卵管和腹膜的浆液性腺癌中RARα蛋白差异细胞定位的新数据。使用针对RARα的亲和纯化抗血清和识别全长雌激素受体分子的单克隆抗体（克隆6F11），我们对冰冻组织切片进行了免疫组织化学，并通过比较两种受体免疫染色肿瘤细胞的百分比来研究RARα与雌激素受体蛋白表达之间的关系。我们的研究结果表明，通过线性回归分析确定，RARα和雌激素受体标记的肿瘤细胞百分比之间存在强线性关系（P < 0.005，r = 0.825）。在RARα阳性肿瘤细胞百分比与组织学分级之间发现适度的负相关关系，证明存在分化依赖性趋势（P < 0.04）。在RARα标记的细胞与临床分期（P = 0.139）、肿瘤起源部位（卵巢与输卵管与腹膜）（P = 0.170）以及原发性与转移性病变（P = 0.561）之间未发现显著关系。因此，尽管肿瘤性疾病的组织学分级高且分期晚，浆液性腺癌仍能够表达RARα和雌激素受体。与癌细胞中RARα的异质性定位相比，在肿瘤浸润淋巴细胞、血管内皮细胞和基质成纤维细胞中存在广泛的RARα免疫反应性，强调了免疫组织化学在准确测定肿瘤标本中RAR/(RXR)含量方面的价值。
