TY - JOUR
T1 - Breast cancer aromatase expression evaluated by the novel antibody 677
T2 - Correlations to intra-tumor estrogen levels and hormone receptor status
AU - Geisler, Jürgen
AU - Suzuki, Takashi
AU - Helle, Hildegunn
AU - Miki, Yasuhiro
AU - Nagasaki, Shuji
AU - Duong, Nhat K.
AU - Ekse, Dagfinn
AU - Aas, Turid
AU - Evans, Dean B.
AU - Lønning, Per E.
AU - Sasano, Hironobu
N1 - Funding Information:
The present work was supported by the Norwegian Cancer Society. This work was also partly supported by the grants from the Japanese Ministry of Health, Labour and Welfare for Researchers on Intractable Diseases, Risk Analysis Research on Food and Pharmaceuticals, and Development of Multidisciplinary Treatment Algorithm with Biomarkers and Modelling of the Decision-making Process with Artificial Intelligence for Primary Breast Cancer. In addition, this work was also supported by Grant-in-Aid for Scientific Research (18390109) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and the Yasuda Medical Foundation.
PY - 2010/2/28
Y1 - 2010/2/28
N2 - Breast cancer tissue estrogen levels on an average exceed plasma as well as benign breast tissue levels. To evaluate the contribution of intra-tumor aromatization to individual tumor estrogen levels (estradiol, E2; estrone, E1; estrone sulfate, E1S), breast cancer tissue sections obtained during mastectomy in 28 postmenopausal breast cancer patients were stained for aromatase protein expression using the aromatase antibody 677. The findings were correlated to intra-tumor estrogen levels determined with a highly sensitive HPLC-RIA. Staining with 677 alone (irrespective of the hormone receptor status) revealed no difference in tumor E2 levels comparing 677+ versus 677- tumors, although a non-significant trend towards higher tumor E1 and E1S levels was observed in 677+ breast cancers. In contrast, tumor levels of E2 were significantly higher in ER+ tumors compared to ER-tumors (P < 0.001) and to benign breast tissue from the same breast (P < 0.001). Analysing the additional effect of positive staining with the aromatase antibody 677 on tumor estrogen levels in the subgroup of ER+ tumors, revealed significantly higher tumor levels of E2 (mean level of 544.7 versus 197.1 fmol/g tissue) as well as a non-significant trend concerning tumor E1 (mean level of 296.9 versus 102.1 fmol/g tissue). The mean tumor tissue E1S level was observed somewhat lower in ER+677+ (103.5 fmol/g) versus ER+677- tumors (190.1 fmol/g). In the subgroup of ER+PgR+ tumors, tissue levels of E2 were also found to be significantly higher among 677+ compared to 677- tumors: 873.2 fmol/g (95% CI 395.9-1925.6) versus 217.9 fmol/g (95% CI 88.8-534.9) (P = 0.015). In conclusion, our results indicate a moderate effect of aromatase enzyme expression evaluated by IHC using the antibody 677 on intra-tumor estrogen levels among ER+ breast cancers. A substantial interindividual variation in the ratios between the individual estrogen fractions suggests additional effects, like alterations in other enzymes to be involved in the intra-tumor estrogen homeostasis.
AB - Breast cancer tissue estrogen levels on an average exceed plasma as well as benign breast tissue levels. To evaluate the contribution of intra-tumor aromatization to individual tumor estrogen levels (estradiol, E2; estrone, E1; estrone sulfate, E1S), breast cancer tissue sections obtained during mastectomy in 28 postmenopausal breast cancer patients were stained for aromatase protein expression using the aromatase antibody 677. The findings were correlated to intra-tumor estrogen levels determined with a highly sensitive HPLC-RIA. Staining with 677 alone (irrespective of the hormone receptor status) revealed no difference in tumor E2 levels comparing 677+ versus 677- tumors, although a non-significant trend towards higher tumor E1 and E1S levels was observed in 677+ breast cancers. In contrast, tumor levels of E2 were significantly higher in ER+ tumors compared to ER-tumors (P < 0.001) and to benign breast tissue from the same breast (P < 0.001). Analysing the additional effect of positive staining with the aromatase antibody 677 on tumor estrogen levels in the subgroup of ER+ tumors, revealed significantly higher tumor levels of E2 (mean level of 544.7 versus 197.1 fmol/g tissue) as well as a non-significant trend concerning tumor E1 (mean level of 296.9 versus 102.1 fmol/g tissue). The mean tumor tissue E1S level was observed somewhat lower in ER+677+ (103.5 fmol/g) versus ER+677- tumors (190.1 fmol/g). In the subgroup of ER+PgR+ tumors, tissue levels of E2 were also found to be significantly higher among 677+ compared to 677- tumors: 873.2 fmol/g (95% CI 395.9-1925.6) versus 217.9 fmol/g (95% CI 88.8-534.9) (P = 0.015). In conclusion, our results indicate a moderate effect of aromatase enzyme expression evaluated by IHC using the antibody 677 on intra-tumor estrogen levels among ER+ breast cancers. A substantial interindividual variation in the ratios between the individual estrogen fractions suggests additional effects, like alterations in other enzymes to be involved in the intra-tumor estrogen homeostasis.
KW - Aromatase antibody 677
KW - Breast cancer
KW - Estradiol
KW - Tissue estrogens
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U2 - 10.1016/j.jsbmb.2009.10.010
DO - 10.1016/j.jsbmb.2009.10.010
M3 - Article
C2 - 19883757
AN - SCOPUS:77950359344
SN - 0960-0760
VL - 118
SP - 237
EP - 241
JO - Journal of Steroid Biochemistry
JF - Journal of Steroid Biochemistry
IS - 4-5
ER -
