title: The prognostic role of progesterone receptor expression in non-small cell lung cancer patients: Gender-related impacts and correlation with disease-specific survival.
abstract: OBJECTIVE
  Progesterone has been shown to impact the development of hormone-sensitive cancers, such as breast and ovarian cancers. Emerging evidence has revealed a possible role of progesterone in the tumorigenesis of other cancers, including lung cancer. Herein, we aimed to elucidate the prevalence and prognostic significance of progesterone receptor (PR) expression in non-small cell lung cancer (NSCLC) tissue.
  
  
  METHODS
  Tumor tissue samples were collected from our patient cohort consisting of 335 NSCLC patients with stage I-IIIA disease. Tissue microarrays (TMAs) were constructed, and immunohistochemical (IHC) analyses were performed to evaluate the PR expression in the tumor epithelial and stromal compartments.
  
  
  RESULTS
  In a univariate analysis, positive PR expression in the stromal tumor compartment (P=0.005) was significantly and independently associated with a favorable outcome for both genders. Furthermore, positive PR expression in tumor epithelial cells (P=0.003) correlated with a poor prognosis for female patients. In a multivariate analysis, positive PR expression in the tumor stroma (P=0.007) was an independent prognostic factor for improved disease-specific survival (DSS). Positive PR expression in tumor epithelial cells emerged as an independent prognostic factor in female patients (P=0.001) for poor DSS.
  
  
  CONCLUSIONS
  We show that PR expression in tumor-surrounding stromal cells is associated with improved DSS for both male and female patients. Additionally, we reveal that positive PR expression in tumor epithelial cells is an independent, unfavorable prognosticator for DSS in female patients, making PR expression a potential marker for prognostic stratification in NSCLC.
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway. Electronic address: kaja.skjefstad@gmail.com.
authors: Kaja
authors: K
authors: Skjefstad
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway.
authors: Elin
authors: E
authors: Richardsen
authors: Department of Clinical Medicine, University of Tromso, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors: Tom
authors: T
authors: Donnem
authors: Department of Clinical Medicine, University of Tromso, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors: Sigve
authors: S
authors: Andersen
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway; Department of Pharmacy, University of Tromso, 9037 Tromso, Norway.
authors: Yury
authors: Y
authors: Kiselev
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway.
authors: Thea
authors: T
authors: Grindstad
authors: Department of Clinical Medicine, University of Tromso, 9037 Tromso, Norway.
authors: Sigurd M
authors: SM
authors: Hald
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway; Department of Pathology, Nordland Central Hospital, 8005 Bodo, Norway.
authors: Khalid
authors: K
authors: Al-Shibli
authors: Department of Clinical Medicine, University of Tromso, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors: Roy M
authors: RM
authors: Bremnes
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway.
authors: Lill-Tove
authors: LT
authors: Busund
authors: Department of Medical Biology, University of Tromso, 9037 Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway.
authors: Samer
authors: S
authors: Al-Saad
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D012189:Retrospective Studies; D012727:Sex Characteristics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins; D011980:Receptors, Progesterone
keywords: Biomarker; NSCLC; Progesterone receptor; Prognostic impact; Tumor stromal cells