title: Expression of ghrelin is correlated to a favorable outcome in invasive breast cancer.
abstract: BACKGROUND
  Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in human mammary glands. However, the clinical implications of the expression of these peptides in breast cancer are unclear. The aim of this study was to investigate the potential clinical value of ghrelin and obestatin as breast cancer biomarkers.
  
  
  METHODS
  A tissue microarray containing breast cancer specimens from 144 patients was immunostained with antibodies directed towards ghrelin and obestatin. Using varying cut-offs, the expression of the two peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox regression analysis was used to assess whether these markers may predict survival of breast cancer patients.
  
  
  RESULTS
  Moderate to strong immunoreactivity for ghrelin and obestatin was observed in 71.5% and 77.1% of the cases, respectively. Ghrelin and obestatin expression was significantly but weakly correlated to low histological grade, estrogen receptor positivity, small tumor size and low proliferation. Only ghrelin expression was significantly correlated to better recurrence-free and breast cancer-specific survival (HR = 0.3-0.4, p = 0.02-0.05) in both uni- and multivariate analyses. The optimal cut-off was any ghrelin expression versus none. Reproducibility between the two readers was very good for both stainings with kappa values of 0.94-1.00.
  
  
  CONCLUSIONS
  Patients with tumors expressing ghrelin had 2.5-3 times lower risk for recurrence or breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with high reproducibility using immunohistochemistry. Further investigations are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer.
authors: Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden. malin.gronberg@medsci.uu.se
authors: Malin
authors: M
authors: Grönberg
authors: Marie-Louise
authors: ML
authors: Fjällskog
authors: Karin
authors: K
authors: Jirström
authors: Eva T
authors: ET
authors: Janson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018276:Carcinoma, Medullary / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D054439:Ghrelin; C505799:obestatin, human