title: Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer.
abstract: BACKGROUND
  The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.
  
  
  METHODS
  On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.
  
  
  RESULTS
  The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.
  
  
  CONCLUSIONS
  Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer.
authors.affiliation: Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway. elin.richardsen@unn.no
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.forename: Rebecca Dale
authors.initials: RD
authors.lastname: Uglehus
authors.forename: Stein Harald
authors.initials: SH
authors.lastname: Johnsen
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D019394:Ki-67 Antigen / Q000235:genetics* / Q000276:immunology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D012306:Risk; D015398:Signal Transduction; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: C508609:IL10 protein, human; D019394:Ki-67 Antigen; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human