Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients.
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.
Innes
H E
HE
Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Clatterbridge Hospital, Wirral CH63 4JY, UK.
Liu
D
D
Barraclough
R
R
Davies
M P A
MP
O'Neill
P A
PA
Platt-Higgins
A
A
de Silva Rudland
S
S
Sibson
D R
DR
Rudland
P S
PS
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
C502296:AGR2 protein, human; D018931:Antineoplastic Agents, Hormonal; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D011960:Receptors, Estrogen