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原发性和转移性三阴性乳腺癌中PELP1蛋白表达显著增加:与GATA3表达的比较及PELP1在三阴性乳腺癌中的潜在作用

Significantly increased PELP1 protein expression in primary and metastatic triple-negative breast carcinoma: comparison with GATA3 expression and PELP1's potential role in triple-negative breast carcinoma.

作者信息

Dang Daniel N, Raj Ganesh, Sarode Venetia, Molberg Kyle H, Vadlamudi Ratna K, Peng Yan

机构信息

Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390-9073.

Department of Urology, UT Southwestern Medical Center, Dallas, TX 75390-9073.

出版信息

Hum Pathol. 2015 Dec;46(12):1829-35. doi: 10.1016/j.humpath.2015.07.023. Epub 2015 Aug 12.

Abstract

PELP1 is a novel coregulator of nuclear hormone receptors and is implicated in playing a role in driving breast cancer and enhancing metastatic potential. The PELP1 protein expression and potential role of PELP1 in triple-negative breast carcinoma (TNBC) have not been well characterized. We investigated PELP1 expression by immunohistochemistry in primary and metastatic triple-negative tumors in human tissues and compared its expression with GATA-binding protein 3 (GATA3), a novel diagnostic marker for TNBC. We examined the expression of PELP1 and GATA3 in 70 primary TNBC cases and found that PELP1 had a significantly higher frequency of expression compared to GATA3 (96% versus 46%; P < .0001). The mean extent score of expression of PELP1 was also significantly higher than GATA3's expression (3.87 ± 0.07 versus 0.91 ± 0.15; P < .0001). PELP1 had stronger staining intensity than GATA3. Furthermore, PELP1 immunoreactivity was consistently maintained in paired primary and metastatic TNBC cases (100%). The frequency of PELP1 expression (100%) in metastatic triple-negative tumors was higher than that of GATA3 (40%) in the same tumors (P < .0001). These findings indicate that PELP1 is a much more sensitive marker than GATA3 for TNBCs. PELP1 may have diagnostic utility for metastatic TNBC in appropriate settings, such as history of primary TNBC in cases where the primary is negative for GATA3, mammaglobin, and GCDFP-15. The diffuse and strong nuclear immunoreactivity of PELP1 in most cases suggests that PELP1 may be a molecular target for the treatment of TNBC. We hope that this study will provide insights into the role of PELP1 in TNBC.

摘要

PELP1是核激素受体的一种新型共调节因子,在驱动乳腺癌和增强转移潜能方面发挥作用。PELP1蛋白表达及其在三阴性乳腺癌(TNBC)中的潜在作用尚未得到充分表征。我们通过免疫组织化学研究了PELP1在人体组织原发性和转移性三阴性肿瘤中的表达,并将其表达与TNBC的新型诊断标志物GATA结合蛋白3(GATA3)进行比较。我们检测了70例原发性TNBC病例中PELP1和GATA3的表达,发现与GATA3相比,PELP1的表达频率显著更高(96%对46%;P <.0001)。PELP1的平均表达范围评分也显著高于GATA3的表达(3.87±0.07对0.91±0.15;P <.0001)。PELP1的染色强度比GATA3更强。此外,在配对的原发性和转移性TNBC病例中,PELP1免疫反应性始终保持(100%)。转移性三阴性肿瘤中PELP1的表达频率(100%)高于同一肿瘤中GATA3的表达频率(40%)(P <.0001)。这些发现表明,对于TNBC,PELP1是比GATA3更敏感的标志物。在适当的情况下,如原发性TNBC病史中,若原发性肿瘤GATA3、乳珠蛋白和GCDFP - 15均为阴性,PELP1可能对转移性TNBC具有诊断价值。在大多数情况下,PELP1弥漫性且强烈的核免疫反应性表明PELP1可能是TNBC治疗的分子靶点。我们希望这项研究能为PELP1在TNBC中的作用提供见解。

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