Research Unit on Women's Health-Institute of Health Research, INCLIVA, 46010 Valencia, Spain.
Department of Pathology, University of Valencia, 46010 Valencia, Spain.
Int J Mol Sci. 2022 Feb 3;23(3):1742. doi: 10.3390/ijms23031742.
The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunohistochemical expression of RANK was examined in a cohort of 135 (benign = 29, borderline = 23 and malignant = 83) EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign = 26, borderline = 13 and malignant = 129) EOCs. RANK protein and mRNA values were increased in malignant vs. benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. Additionally, a trend of increased RANK values with staging was observed for the mucinous and serous histotype. Thus, increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. Moreover, in some EOC histotypes, RANK expression is additionally associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity.
核因子 κB 受体激活剂（RANK）正逐渐被认为是肿瘤发生的主要调节因子，但它在妇科癌症中的作用仍大多未被探索。我们研究了根据恶性程度和肿瘤分期，上皮性卵巢癌（EOC）中 RANK 蛋白和 mRNA 表达是否存在分级。我们在 135 例上皮性卵巢癌（良性=29 例，交界性=23 例，恶性=83 例）的队列中检查了 RANK 的免疫组织化学表达。在另一组 168 例上皮性卵巢癌（良性=26 例，交界性=13 例，恶性=129 例）的队列中，我们检测了野生型和截断型 RANK mRNA 异构体的定量。与良性或交界性相比，在浆液性、黏液性和子宫内膜样癌亚型中，恶性肿瘤的 RANK 蛋白和 mRNA 值增加。此外，黏液性和浆液性组织型的 RANK 值随分期的增加而增加。因此，RANK 的表达增加似乎与 EOC 疾病向恶性肿瘤的发生发展有关。此外，在一些上皮性卵巢癌组织类型中，RANK 表达还与肿瘤侵袭性的临床病理标志物相关，表明其在肿瘤活性的进一步进展中起作用。
