Theocharis Stamatios, Giaginis Constantinos, Gourzi Stefania, Alexandrou Paraskevi, Tsourouflis Gerasimos, Sarantis Panagiotis, Danas Eugene, Michail Artemis, Tsoukalas Nikolaos, Pergaris Alexandros, Politis Panagiotis K, Nakopoulou Lydia
First Department of Pathology, Medical School, University of Athens, 11527 Athens, Greece.
Department of Food Science and Nutrition, University of the Aegean, 81400 Lemnos, Greece.
Diagnostics (Basel). 2021 Oct 20;11(11):1946. doi: 10.3390/diagnostics11111946.
Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed paraffin-embedded breast invasive carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes, tumor cells' proliferative capacity, and overall disease-free patients' survival. Additionally, the expression of PXR was examined on human breast carcinoma cell lines of different histological grade, hormonal status, and metastatic potential. PXR positivity was noted in 79 (53.4%) and high PXR expression in 48 (32.4%), out of 148 breast carcinoma cases. High PXR expression was positively associated with nuclear grade ( = 0.0112) and histological grade of differentiation ( = 0.0305), as well as with tumor cells' proliferative capacity ( = 0.0051), and negatively with luminal A subtype ( = 0.0295). Associations between high PXR expression, estrogen, and progesterone receptor negative status were also recorded ( = 0.0314 and = 0.0208, respectively). High PXR expression was associated with shorter overall patients' survival times (log-rank test, = 0.0009). In multivariate analysis, high PXR expression was identified as an independent prognostic factor of overall patients' survival (Cox-regression analysis, = 0.0082). PXR expression alterations were also noted in breast cancer cell lines of different hormonal status. The present data supported evidence that PXR was related to a more aggressive invasive breast carcinoma phenotype, being a strong and independent poor prognosticator.
孕烷X受体（PXR）通过直接影响致癌作用或诱导药物相互作用及化疗耐药性参与人类癌症。本研究评估了PXR在浸润性乳腺癌中的表达的临床意义。采用免疫组织化学方法对148例患者福尔马林固定石蜡包埋的乳腺浸润癌组织切片进行PXR蛋白表达评估，并与临床病理参数、分子表型、肿瘤细胞增殖能力及患者无病生存期进行相关性分析。此外，还检测了不同组织学分级、激素状态和转移潜能的人乳腺癌细胞系中PXR的表达。在148例乳腺癌病例中，79例（53.4%）PXR呈阳性，48例（32.4%）PXR高表达。PXR高表达与核分级（P = 0.0112）、组织学分化程度（P = 0.0305）以及肿瘤细胞增殖能力（P = 0.0051）呈正相关，与腔面A型亚型（P = 0.0295）呈负相关。还记录到PXR高表达与雌激素和孕激素受体阴性状态之间的关联（分别为P = 0.0314和P = 0.0208）。PXR高表达与患者总生存期缩短相关（对数秩检验，P = 0.0009）。多因素分析显示，PXR高表达是患者总生存期的独立预后因素（Cox回归分析，P = 0.0082）。在不同激素状态的乳腺癌细胞系中也观察到PXR表达改变。目前的数据支持PXR与侵袭性更强的浸润性乳腺癌表型相关，是一个强有力的独立不良预后指标这一证据。
