Expression of long-form prolactin receptor is associated with lower disease-free and overall survival in node-negative breast cancer patients.

BACKGROUND

Breast cancer is the most frequent female malignancy in Thailand. Prolactin (PRL) and prolactin receptor (PRLR) play an important role in normal breast development and carcinogenesis of breast cancer. There are two major isoforms of PRLR, consisting of long-form (LF-PRLR) and short-form (SF-PRLR) that stimulate different signaling pathways. This study aims to explore the associations between all PRLR isoforms (all-PRLR) and LF-PRLR with clinicopathological parameters in breast cancer patients.

METHODS

A total of 340 patients were recruited from January 2009 to December 2015. Expressions of PRLR in breast cancer tissue were determined by immunohistochemistry using specific antibodies that recognize different domains of PRLR (B6.2 for all-PRLR and H-300 for LF-PRLR). The associations between all-PRLR and LF-PRLR expressions with clinicopathological parameters were evaluated.

RESULTS

Expression of all-PRLR was observed in 86.2% of all patients while LF-PRLR expression was observed in 54.4%. All-PRLR was co-expressed with estrogen receptor (ER) and progesterone receptor (PR). LF-PRLR expression was associated with high grade tumor and human epidermal growth factor receptor-2 (HER2) overexpression (P=0.010 and <0.001, respectively). Subgroup analysis revealed that LF-PRLR expression was the independent predictor for lower disease-free survival (DFS) in node-negative breast cancer patients with high expression of all-PRLR [hazard ratio (HR): 5.224, 95% confidence interval (CI): 1.089-25.064, P=0.039].

CONCLUSIONS

The presence of LF-PRLR in the patients with high expression of all-PRLR was associated with adverse outcome. Evaluation of all-PRLR and LF-PRLR might be used as novel prognosticators in node-negative breast cancers.