Expression of amphiregulin and epidermal growth factor receptor in human breast cancer: analysis of autocriny and stromal-epithelial interactions.
Amphiregulin (AR) and its receptor, epidermal growth factor receptor (EGFR), were evaluated by dual immunostaining in a series of 84 invasive ductal breast carcinoma specimens, 33 of which were from locally advanced inflammatory (T4d) cancer. Co-expression of AR and EGFR was always found in non-malignant breast tissues adjacent to tumours (24/24). Alternatively, expression of AR and EGFR was found in invasive epithelial tumour cells in 50% and 17.8% of specimens, respectively. In tumour stroma, 59.5% and 30.9% of specimens, respectively, were positively stained. By univariate analysis, AR and EGFR expression in invasive carcinomas was correlated with large tumour size, inflammatory carcinoma, node involvement, Bloom-Richardson (SBR) grade III, and absence of oestrogen receptor. EGFR expression in stromal cells was correlated with non-inflammatory carcinoma. A putative autocrine loop with AR and EGFR expression in invasive carcinoma was detected in 14.3% of cases. Stromal expression of AR and EGFR expression in invasive tumour cells was detected in 11.9% of cases and related to poor prognostic parameters. By multivariate analysis, AR expression in invasive tumour was strongly related to inflammatory carcinoma (p=0.005) and marginally related to SBR grade III (p=0.07). EGFR expression in invasive tumour and stromal cells was correlated with absence of oestrogen receptor and non-inflammatory carcinoma (p=0.002 and p=0.015, respectively).
Ma
L
L
Laboratoire de Pharmacologie Expérimentale et Clinique, INSERM EPI 99-32, Institut de Génétique Moléculaire, 27 Rue Juliette Dodu, 75010 Paris, France.
de Roquancourt
A
A
Bertheau
P
P
Chevret
S
S
Millot
G
G
Sastre-Garau
X
X
Espié
M
M
Marty
M
M
Janin
A
A
Calvo
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066258:Amphiregulin; D019898:Autocrine Communication / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D066255:EGF Family of Proteins; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
C587848:AREG protein, human; D066258:Amphiregulin; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D066246:ErbB Receptors