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105 Interaction of different hormonal compounds on the metabolism of oestrone sulphate by breast cancer tissue
55s
103
Estrogen and
Binding
Biochemical
Sites
(EBS)
in
Human
Breast
Cancer
-
Correlation
of
the
Histochemical
Technique.
+:Women’s College Hospital, **University of Toronto, Toronto, Ontario, Canada Material was obtained from 248 consecutive cases of primary human breast cancer done at Canada and studied for the histochemical localization Women’s College Hospital, Toronto, Evaluation of the estrogen receptors using the of EBS using fluoresceinated estradiol. Frozen sections stained Dextran coated charcoal technique was done on the same tumour. The inwith the tracer were examined and the percentage of positive cells recorded. A l+ fluorescence is considered negatensity of the fluorescence is graded 1+ to 3+. The tumours are divided into three groups tive regardless of the percentage of cells. Hanna,
Wedad
Mt,
Mobbs,
Betty
G@;
Group 1 - >gO% definitely positive (59 according to the percentage of positive cells. cases), Group 2 - ~10% definitely negative (100 cases) and Group 3 - intermediate group The results of the biochemical assay are correlated with the histochemical (89 cases). technique in the first and second groups only in view of the absence of an acceptable The concordance between the two techniques was cut off point for the latter technique. found to be 75% in the first group and 65% in the second group. The histochemical technique is simple and inexpensive and can be done in any surgical pathology laboratory. Clinical follow-ups are however, mandatory to evaluate the accuracy of this technique and its role singly or in combination with the biochemical assay to select breast cancer patients for endocrine therapy.
104
HETEROGENEITY OF LOW SALT 4s OESTROGEN RECEPTOR FROM HUMAN BREAST CANCER WITH RESPECT TO DNA BINDING. Salman Hydec and Robin Leake, Department of Biochemistry, University of Glasgow, Glasgow G12 SQQ, Scotland. The interaction with DNA of oestrogen receptor complex from human breast tumour cytosol has been studied. In the absence of exogenous DNA, the soluble oestrogen receptor sedimented at 4s and/or 8s regions in low salt sucrose density gradients. Incubation of tumour cytosol with soluble calf thymus DNA almost always resulted in the 8s form interacting with DNA and sedimenting to the bottom of the tube. In contrast the 45 form seemed to comprise two populations - one which bound to DNA in a manner similar to the 8s form, whereas the other had lost DNA binding ability and remained in the 4s peak on the gradient. These two populations of 45 can be present either independently or as a mixture. These results suggest that 45 receptor in human breast cancer may comprise of both a proteolysed form and a dissociated form of the 85 receptor. Only the latter form retains the DNA binding site(s).
105
INTERACTION BY BREAST
OF DIFFERENT
HORMONAL COMPOUNDS ON THE METABOLISM
OF OESTRONE SULPHATE
CANCER TISSUE.
Nils Wilking and Kjell Carlstrom, Surgical clinic, Sabbatsberg hospital, Box 6401, S-113 82 Stockholm, Sweden and Dep. of Obstet. and Gynaecol. Hudding hospital, Sweden. Most of the interest concerning intratumoural oestradiol formation has been focused on the aromatase process. However other oestradiol precursors may play a significant role. We have investigated the ability of turnout-homogenates to metabolize oestrone sulphate; the most abundant oestrogen in the non pregnant female. Significant amounts of both oestrone and oestradiol were formed by the tumours. The effects of different hormonally active compounds on this transformation were examined. Tamoxifen stimulated and danazol inhibited the formation of oestradiol while aminoglutethimide had no effect. The oestrone sulphatase activity in breast tumour microsomes was stimulated by tamoxifen and medroxyprogesterone acetate and strongly inhibited by danazol. Aminoglutethimide and trilostane had no effect on this process.
103
Estrogen and
Binding
Biochemical
Sites
(EBS)
in
Human
Breast
Cancer
-
Correlation
of
the
Histochemical
Technique.
+:Women’s College Hospital, **University of Toronto, Toronto, Ontario, Canada Material was obtained from 248 consecutive cases of primary human breast cancer done at Canada and studied for the histochemical localization Women’s College Hospital, Toronto, Evaluation of the estrogen receptors using the of EBS using fluoresceinated estradiol. Frozen sections stained Dextran coated charcoal technique was done on the same tumour. The inwith the tracer were examined and the percentage of positive cells recorded. A l+ fluorescence is considered negatensity of the fluorescence is graded 1+ to 3+. The tumours are divided into three groups tive regardless of the percentage of cells. Hanna,
Wedad
Mt,
Mobbs,
Betty
G@;
Group 1 - >gO% definitely positive (59 according to the percentage of positive cells. cases), Group 2 - ~10% definitely negative (100 cases) and Group 3 - intermediate group The results of the biochemical assay are correlated with the histochemical (89 cases). technique in the first and second groups only in view of the absence of an acceptable The concordance between the two techniques was cut off point for the latter technique. found to be 75% in the first group and 65% in the second group. The histochemical technique is simple and inexpensive and can be done in any surgical pathology laboratory. Clinical follow-ups are however, mandatory to evaluate the accuracy of this technique and its role singly or in combination with the biochemical assay to select breast cancer patients for endocrine therapy.
104
HETEROGENEITY OF LOW SALT 4s OESTROGEN RECEPTOR FROM HUMAN BREAST CANCER WITH RESPECT TO DNA BINDING. Salman Hydec and Robin Leake, Department of Biochemistry, University of Glasgow, Glasgow G12 SQQ, Scotland. The interaction with DNA of oestrogen receptor complex from human breast tumour cytosol has been studied. In the absence of exogenous DNA, the soluble oestrogen receptor sedimented at 4s and/or 8s regions in low salt sucrose density gradients. Incubation of tumour cytosol with soluble calf thymus DNA almost always resulted in the 8s form interacting with DNA and sedimenting to the bottom of the tube. In contrast the 45 form seemed to comprise two populations - one which bound to DNA in a manner similar to the 8s form, whereas the other had lost DNA binding ability and remained in the 4s peak on the gradient. These two populations of 45 can be present either independently or as a mixture. These results suggest that 45 receptor in human breast cancer may comprise of both a proteolysed form and a dissociated form of the 85 receptor. Only the latter form retains the DNA binding site(s).
105
INTERACTION BY BREAST
OF DIFFERENT
HORMONAL COMPOUNDS ON THE METABOLISM
OF OESTRONE SULPHATE
CANCER TISSUE.
Nils Wilking and Kjell Carlstrom, Surgical clinic, Sabbatsberg hospital, Box 6401, S-113 82 Stockholm, Sweden and Dep. of Obstet. and Gynaecol. Hudding hospital, Sweden. Most of the interest concerning intratumoural oestradiol formation has been focused on the aromatase process. However other oestradiol precursors may play a significant role. We have investigated the ability of turnout-homogenates to metabolize oestrone sulphate; the most abundant oestrogen in the non pregnant female. Significant amounts of both oestrone and oestradiol were formed by the tumours. The effects of different hormonally active compounds on this transformation were examined. Tamoxifen stimulated and danazol inhibited the formation of oestradiol while aminoglutethimide had no effect. The oestrone sulphatase activity in breast tumour microsomes was stimulated by tamoxifen and medroxyprogesterone acetate and strongly inhibited by danazol. Aminoglutethimide and trilostane had no effect on this process.