Prolactin Receptor Expression is an Independent Favorable Prognostic Marker in Human Breast Cancer

Abstract

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.

Zinc Finger Homeodomain Factor Zfhx3 Is Essential for Mammary Lactogenic Differentiation by Maintaining Prolactin Signaling Activity

“…The decrease of phosphorylated STAT5 is correlated with poorer patient survival and predicts both poor clinical outcome and increased risk of antiestrogen therapy failure (61)(62)(63)(64)(65). PRLR has been shown to suppress epithelial-mesenchymal transition and invasiveness of breast cancer cells (66), and PRLR expression is significantly down-regulated in invasive breast cancer, the down-regulation being associated with lymph node metastasis, lower tumor grade, and metastasis-free survival in breast cancer patients (67). Consistent with the findings of p-STAT5 and PRLR expression, the ZFHX3 mRNA level has also been shown to be frequently down-regulated in human breast cancer (68), which is likely mediated by hemizygous deletion (69), and again downregulation was correlated with a worse patient survival (68).…”

Prolactin receptor in breast cancer: marker for metastatic risk

“…There was no evidence of association of PRLR expression with hormone receptors, although an association of PRLR expression and the luminal A subtype was observed, and there was no evidence of association with the basal subtype. Analysis of 21 subtypes (in a subset of 1379 patients) resulted in a significant association of PRLR expression with better distant metastasis-free survival in luminal B (PAM50 and Hu classifications) patients (Hachim et al 2016a). In future, it would be very interesting to discover which receptor variants are predominantly expressed in each of these molecular subtypes and which pathway may be preferentially activated within each subtype.…”

“…Using a small TMA (102 patients) with immunohistochemistry, analysis of PRLR levels and its gene expression was undertaken (Hachim et al 2016a). Cores of the small TMA were reclassified on the basis of immunohistochemical markers, as surrogates of the molecular subtype, and found the PRLR (polyclonal antibody H-300 to the receptor intracellular domain) was present in luminal, A, luminal B and Her2-enriched, but not in triple-negative patient tumors.…”

“…Cores of the small TMA were reclassified on the basis of immunohistochemical markers, as surrogates of the molecular subtype, and found the PRLR (polyclonal antibody H-300 to the receptor intracellular domain) was present in luminal, A, luminal B and Her2-enriched, but not in triple-negative patient tumors. A larger analysis was carried out at the mRNA levels in a cohort of the GOBO (1881 patients) database (Hachim et al 2016a). There was no evidence of association of PRLR expression with hormone receptors, although an association of PRLR expression and the luminal A subtype was observed, and there was no evidence of association with the basal subtype.…”

The Role of Prolactin in the Development of Mammary Gland Pathology

“…Загалом, експресія ПРЛ-Р була ви-ща при високодиференційованих пухлинах. Також тривала виживаність без віддалених метастазів з РМЗ була пов'язана з експресією,з достовірністю (р<0,01) [20].…”