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

Doonyapat Sa-Nguanraksa; Kwanlada Mitpakdi; Norasate Samarnthai; Thanawat Thumrongtaradol; Pornchai O-Charoenrat

doi:10.21037/gs-20-569

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

Gland Surg. 2021 Jan;10(1):130-142. doi: 10.21037/gs-20-569.

Authors

Doonyapat Sa-Nguanraksa¹, Kwanlada Mitpakdi², Norasate Samarnthai³, Thanawat Thumrongtaradol¹, Pornchai O-Charoenrat⁴

Affiliations

¹ Division of Head Neck and Breast Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
² Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁴ Breast Center, Medpark Hospital, Bangkok, Thailand.

Abstract

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.

Keywords: Breast cancer; immunohistochemistry; long-isoform prolactin receptor (long-isoform PRLR); prolactin receptor (PRLR).