title: Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients.
abstract: The anterior gradient protein-2 (AGR2) is inducible by oestrogen and itself can induce metastasis in a rat model for breast cancer. Here, a rabbit antibody to recombinant human AGR2 was used to assess its prognostic significance in a retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal therapy. The antibody stains 66% of breast carcinomas to varying degrees. The percentage of positive carcinoma cells in tumours directly correlates with the level of AGR2 mRNA (Spearman's rank correlation, P = 0.0007) and protein (linear regression analysis r2 = 0.95, P = 0.0002). There is a significant association of staining of carcinomas for AGR2 with oestrogen receptor alpha (ERalpha) staining and with low histological grade (both Fisher's Exact test P<0.0001). In the ERalpha-positive cases, but not the ERalpha-negative cases, when subdivided into the separate staining classes for AGR2, there is a significantly progressive decrease in patient survival with increased staining (log rank test, P = 0.006). The significant association of staining for AGR2 with patient death over a 10-year period (log rank test P = 0.007, hazard ratio = 3) only becomes significant at 6 years of follow-up. This may be due to the cessation of adjuvant hormonal therapy at an earlier time, resulting in adverse re-expression of the metastasis-inducing protein AGR2.
authors.affiliation: Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Clatterbridge Hospital, Wirral CH63 4JY, UK.
authors.forename: H E
authors.initials: HE
authors.lastname: Innes
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Barraclough
authors.forename: M P A
authors.initials: MP
authors.lastname: Davies
authors.forename: P A
authors.initials: PA
authors.lastname: O'Neill
authors.forename: A
authors.initials: A
authors.lastname: Platt-Higgins
authors.forename: S
authors.initials: S
authors.lastname: de Silva Rudland
authors.forename: D R
authors.initials: DR
authors.lastname: Sibson
authors.forename: P S
authors.initials: PS
authors.lastname: Rudland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D008875:Middle Aged; D009088:Mucoproteins; D009362:Neoplasm Metastasis; D015513:Oncogene Proteins; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011506:Proteins / Q000032:analysis / Q000502:physiology*; D011960:Receptors, Estrogen / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: C502296:AGR2 protein, human; D018931:Antineoplastic Agents, Hormonal; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D011960:Receptors, Estrogen