Hachim Ibrahim Y, Hachim Mahmood Y, Lopez Vanessa M, Lebrun Jean-Jacques, Ali Suhad
Departments of *Medicine, Division of Hematology ‡Medicine, Division of Medical Oncology, McGill University Health Centre, McGill University, Montreal, QC, Canada †Medical Microbiology Department, RAK Medical and Health Sciences University, Ras al-Khaimah, UAE.
Appl Immunohistochem Mol Morphol. 2016 Apr;24(4):238-45. doi: 10.1097/PAI.0000000000000178.
Prolactin (PRL) hormone plays an important role in the development of the mammary gland and terminal differentiation of the mammary epithelial cells. While initial studies suggested that PRL may contribute to the development of breast cancer through PRL/prolactin receptor (PRLR) autocrine function, mounting evidence indicate a different role for PRL, highlighting this hormone as a regulator of epithelial plasticity and as a potential tumor suppressor. To gain further insights into the role of PRL in human breast carcinogenesis, immunohistochemistry analyses of PRLR protein expression levels using tissue microarray of 102 cases were done in comparison with various clinical/pathologic parameters and molecular subtypes. In addition, gene expression level of PRLR was also evaluated in relation to intrinsic molecular subtypes, tumor grade, and patient outcome using GOBO database for 1881 breast cancer patients. Interestingly, PRLR expression was found to be significantly downregulated in invasive breast cancer (21.4%) in comparison with normal/benign (80%) and in situ carcinoma (60%) (P=0.003498). Moreover, PRLR expression was associated with lymph node negativity and low-grade well-differentiated tumors. PRLR expression was strongest in luminal A subtype, and was virtually undetectable in the worse prognosis triple-negative breast cancer subtype (P=0.00001). Furthermore, PRLR expression was independent of ER, PR, HER-2, and P53 status. Finally, PRLR expression was significantly (P<0.01) associated with prolonged distant metastasis-free survival in breast cancer patients. In conclusion, our results highlight PRLR as an independent predictor of favorable prognosis in human breast cancer.
催乳素（PRL）激素在乳腺发育和乳腺上皮细胞的终末分化中起着重要作用。虽然最初的研究表明，PRL可能通过PRL/催乳素受体（PRLR）自分泌功能促进乳腺癌的发展，但越来越多的证据表明PRL具有不同的作用，突出了这种激素作为上皮可塑性调节剂和潜在肿瘤抑制因子的作用。为了进一步深入了解PRL在人类乳腺癌发生中的作用，我们使用102例组织芯片对PRLR蛋白表达水平进行了免疫组织化学分析，并与各种临床/病理参数和分子亚型进行了比较。此外，还使用GOBO数据库对1881例乳腺癌患者的PRLR基因表达水平与内在分子亚型、肿瘤分级和患者预后进行了评估。有趣的是，与正常/良性（80%）和原位癌（60%）相比，浸润性乳腺癌中PRLR表达显著下调（21.4%）（P=0.003498）。此外，PRLR表达与淋巴结阴性和低级别高分化肿瘤相关。PRLR表达在腔面A型亚型中最强，在预后较差的三阴性乳腺癌亚型中几乎检测不到（P=0.00001）。此外，PRLR表达与ER、PR、HER-2和P53状态无关。最后，PRLR表达与乳腺癌患者远处无转移生存期延长显著相关（P<0.01）。总之，我们的结果突出了PRLR作为人类乳腺癌预后良好的独立预测因子。
