Expression of aromatase and estrogen sulfotransferase in preinvasive and invasive breast cancer.
OBJECTIVE
Intratumoral estradiol levels in postmenopausal women with breast cancer are thought to be mainly regulated by the aromatase-mediated conversion from androgens and estrogen sulfotransferase (EST)-mediated reduction of bioavailability. While in invasive breast cancer (IBC) the role of both enzymes has been extensively studied and has led to the use of aromatase inhibitors as a key therapeutic strategy, comparably little is still known about their role in the local regulation of estradiol in ductal carcinoma in situ (DCIS).


METHODS
We have performed immunohistochemistry to investigate the expression of aromatase and sulfotransferase in custom-made breast cancer tissue arrays containing 96 samples of pure DCIS and in 104 tumor biopsies which contain both, DCIS and invasive components.


RESULTS
We found that aromatase was equally detectable in epithelial components of both, DCIS and IBC (P = 0.884, Chi square test). However, stromal aromatase expression was significantly higher in IBC compared to adjacent DCIS components (P = 0.034, Chi square test). Whereas no significant difference was observed for epithelial aromatase expression in high versus non-high grade DCIS (P = 0.735 Chi square test), epithelial EST levels were found to be significantly down-regulated in high-grade DCIS compared to non-high grade cases (P = 0.042).


CONCLUSIONS
We have demonstrated the presence of both aromatase and EST in malignant epithelium and adjacent stromal fibroblasts in DCIS. Lower stromal aromatase expression in preinvasive breast cancer and lower EST levels in high-grade DCIS suggest that the net effect of intratumoral estradiol (E2)-modulating enzymes results in lower local E2 levels in earlier stages of breast tumorigenesis.
Hudelist
G
G
Department of Obstetrics and Gynecology, Division of Special Gynecology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Wülfing
P
P
Kersting
C
C
Burger
H
H
Mattsson
B
B
Czerwenka
K
K
Kubista
E
E
Gschwantler-Kaulich
D
D
Fink-Retter
A
A
Singer
C F
CF
D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000473:pathology; D004848:Epithelium / Q000201:enzymology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000201:enzymology*; D015238:Sulfotransferases / Q000378:metabolism*; D046888:Tissue Array Analysis
D001141:Aromatase; D015238:Sulfotransferases; C020122:estrone sulfotransferase