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COMPUTER ASSISTED MORPHOMETRIC MEASUREMENTS OF THE MICROVASCULARIZATION AND HORMONAL RECEPTOR EXPRESSION IN NORMAL, HYPERPLASTIC, AND NEOPLASTIC BREAST TISSUES
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8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
192 COMPUTER ASSISTED MORPHOMETRIC MEASUREMENTS OF THE MICROVASCULARIZATION AND HORMONAL RECEPTOR EXPRESSION IN NORMAL, HYPERPLASTIC, AND NEOPLASTIC BREAST TISSUES M. Safwat 1 , F. Habib 2 , A. Elayat 1 , N. Oweiss 3 , S. Reffat 4 , S. Algaidi 1 . 1 Faculty of Medicine, Anatomy Department, Al-Madinah Al-Munawarah, Saudi Arabia; 2 Faculty of Medicine, Obstetrics & Gynacology Department, Al-Madinah Al-Munawarah, Saudi Arabia; 3 Faculty of Medicine, Pathology Department, Al-Madinah Al-Munawarah, Saudi Arabia; 4 Faculty of Medicine, Surgery Department, Al-Madinah Al-Munawarah, Saudi Arabia Objectives: To evaluate the quantitative distribution of microvasularization as well as estrogen/progesterone receptor expression in normal breast tissues, and to compare the results with benign, and malignant human breast lesions using immunohistochemical analysis (mouse anti-human CD34, anti-ER and anti-PR), and computer-assisted morphometric measurements. Also, the relationship between microvascularization and hormonal receptor expression was assessed. Methods: Normal breast tissues (15 specimens), benign (15 fibrocystic diseases, and 10 fibroadenomas) and malignant breast lesions (25 invasive ductal carcinomas); 12 pre-menopausal, and 13 post-menopausal patients were collected from King Fahd Hospital, Saudi Arabia. Results: Computer assisted morphometric measurements of the vascular count, microvascular density and vascular area ratio were significantly enhanced in hyperplastic and neoplastic lesions as compared to normal breast specimens. Also, significant differences were observed in these vascular parameters between the three grades of invasive ductal carcinomas with the highest parameters in grade III. No significant differences were detected in the vascular parameters between premenopausal and postmenopausal cancer patients. Estrogen receptor expression was less in premenopausal as compared to postmenopausal women. No correlation was detected between the vascular parameters and the hormonal receptor expressions in normal breast tissues; or in different grades of malignancy. Conclusions: The computerized image analysis morphometric measurements of the results established several parameters in normal breast that can be beneficially used as a base for characterizing angiogenesis in breast carcinomas. By this way, a data base necessary for understanding when normal cells become malignant can be applied. Keywords: Microvascularization, hormonal receptors, computerized image analysis, breast tissue.
be due to a lower cytochrome activity and a higher glutathione peroxidase activity. We suggest that the higher UCP2 and UCP5 protein levels are involved in this lower oxidative stress. Keywords: Mammary carcinomas, oxidative stress, UCPs.
194 TRANSDUCTION SIGNALING PATHWAYS IN ESTROGEN RECEPTOR-POSITIVE/NEGATIVE MAMMARY CARCINOMAS J. Sastre-Serra 1 , M. Company 2 , A. Valle 1 , P. Roca 1 , G. Catalán 2 , J. Oliver 1 . 1 Grup de Metabolisme Energètic i Nutrició, Dpt. de Biologia Fonamental i Ciències de la Salut, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, and CIBERobn (CB06/03), Instituto de Salud Carlos III, Palma, Spain; 2 Hospital Son Llàtzer, Palma, Spain Reactive oxygen species (ROS) are intermediate cell metabolism products which not only act inside cells producing damage to lipids, proteins and nucleic acids, but whose levels can fluctuate in response to extracellular and intracellular signals too, working as second messengers in specific signalling cascades - like MAPKs (mitogen-activated protein kinases) involved in the cell process of differentiation, proliferation and apoptosis. Objectives: To compare activation state of these signalling cascades induced by oxidative stress in infiltrating ductal mammary carcinomas, positive or negative to estrogen receptors (ER+ and ER-). Methods: Twelve tumours (six of each group) were homogenized. Parameters of oxidative damage were analysed. AKT, SAPK/JNK, STAT3, ERK1/2 protein levels and phosphorylation state were determined. The ratio of phosphorylated protein versus total protein was also determined. Results: Oxidative stress was lower in ER+ tumours with respect to ER-. However, AKT, p-SAPK/JNK, p-ERK2 and ERK2 proteins levels were higher in ER- tumours. Phosphorylation ratios of SAPK/JNK, STAT3 and ERK1 with respect to their total protein levels were higher in ER-. Conclusions: The lower activation of oxidative stress-modulated signalling pathways by lower phosphorylation of proteins is a consequence of the lower oxidative stress observed in ER+ tumours. We suggest that this lower activation could be due to a higher activity of antioxidant enzymes such as glutathione peroxidase, and higher UCP2 and UCP5 protein levels in ER+ tumours. Keywords: Mammary carcinomas, oxidative stress, oxidative stressmodulated signalling pathways.
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STUDY OF REDOX STATE IN ESTROGEN RECEPTOR-POSITIVE/NEGATIVE MAMMARY CARCINOMAS
PHENOMENOLOGICAL STUDY OF PHANTOM BREAST SYNDROME
J. Sastre-Serra 1 , M. García-Bonafé 2 , J. Oliver 1 , G. Catalán 2 , P. Roca 1 . 1 Grup de Metabolisme Energètic i Nutrició, Dpt. de Biologia Fonamental i Ciències de la Salut, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, and CIBERobn (CB06/03), Instituto de Salud Carlos III, Palma, Spain; 2 Hospital Son Llàtzer, Palma, Spain
A. Spyropoulou 1 , C. Markopoulos 2, I. Zervas 1 , G. Christodoulou 3 , C. Papageorgiou 3 . 1 Women’s Mental Health Clinic, Eginition Hospital, First Department of Psychiatry, University of Athens, Athens, Greece; 2 Breast Unit, Laiko General Hospital, Second Department of Propedeutic Surgery, University of Athens, Athens, Greece; 3 Eginition Hospital, First Department of Psychiatry, University of Athens, Athens, Greece
Reactive oxygen species (ROS) are cell metabolism products which not only cause damage to cell structure, but also play a significant role in several chronic pathologies, like cancer. Estrogens are important mitogenic signals in breast cancer, regulating the expression of antioxidant enzymes and decreasing ROS production. Oxidative stress is the imbalance between ROS production and their removal by enzymatic and non-enzymatic antioxidant systems, with UCPs playing a possible key role as antioxidants. Objectives: To investigate the effects of estrogens on oxidative stress in infiltrating ductal mammary carcinomas, positive or negative to estrogen receptors (ER+ and ER-). Methods: Twelve tumours (six of each group) were homogenized. Parameters of oxidative damage as well as mtDNA content were assayed. Mitochondrial cytochrome c oxidase, Mn-superoxide dismutase, Cu/Znsuperoxide dismutase and glutathione peroxidase activities were also measured. Cytochrome c oxidase subunit IV and also UCP2 and UCP5 protein levels were determined. Results: Oxidative damage in proteins, cytochrome c oxidase activity and protein levels were higher in ER- with respect to ER+ tumours. The mtDNA content was similar in both types of tumours. Glutathione peroxidase activity, but not superoxide dismutase, and UCP2 and UCP5 protein levels were lower in ER- tumours. Conclusions: The lower oxidative damage in ER+ with respect to ER- could
Objectives: To better understand the phenomenology of phantom breast syndrome, which represents the experience of the continued presence of the breast after mastectomy and to look at its clinical relevance to phantom limb phenomena. Methods: One hundred and five (105) patients who had undergone mastectomy for non-metastatic breast cancer were interviewed by means of a structured questionnaire. Results: The group of women who experienced phantom breast syndrome consisted of 24 women (22.9%) with a mean age of 56.4 years (SD=10.5 years) Phantom pain was experienced by 6 patients (25%), who concurrently had other type of sensations, such as “itching” and “pinpricks”, at the phantom breast. In the majority of cases phantom experience had the size (88.9%), shape (76.5%) and weight (64.7%) of the normal breast and was localized in the entire breast (50%). Phantom sensations were rather indifferent for 65.3% of PBS patients, pleasant for 13.0% and unpleasant for 21.7%. Conclusions: PBS seems to represent a non disturbing phenomenon which usually is localized over the entire breast and is felt to have the qualities of a normal breast. Features such as prevalence, clinical relevance and localization seem to give PBS distinct characteristics in comparison to what is known about phantom limb. These differences could be partially attributed to the small representation of the breast in the somatosensory cortex and the absence of kinesthesis.
8th European Congress on Menopause (EMAS) / Maturitas 63, Supplement 1 (2009) S1–S136
192 COMPUTER ASSISTED MORPHOMETRIC MEASUREMENTS OF THE MICROVASCULARIZATION AND HORMONAL RECEPTOR EXPRESSION IN NORMAL, HYPERPLASTIC, AND NEOPLASTIC BREAST TISSUES M. Safwat 1 , F. Habib 2 , A. Elayat 1 , N. Oweiss 3 , S. Reffat 4 , S. Algaidi 1 . 1 Faculty of Medicine, Anatomy Department, Al-Madinah Al-Munawarah, Saudi Arabia; 2 Faculty of Medicine, Obstetrics & Gynacology Department, Al-Madinah Al-Munawarah, Saudi Arabia; 3 Faculty of Medicine, Pathology Department, Al-Madinah Al-Munawarah, Saudi Arabia; 4 Faculty of Medicine, Surgery Department, Al-Madinah Al-Munawarah, Saudi Arabia Objectives: To evaluate the quantitative distribution of microvasularization as well as estrogen/progesterone receptor expression in normal breast tissues, and to compare the results with benign, and malignant human breast lesions using immunohistochemical analysis (mouse anti-human CD34, anti-ER and anti-PR), and computer-assisted morphometric measurements. Also, the relationship between microvascularization and hormonal receptor expression was assessed. Methods: Normal breast tissues (15 specimens), benign (15 fibrocystic diseases, and 10 fibroadenomas) and malignant breast lesions (25 invasive ductal carcinomas); 12 pre-menopausal, and 13 post-menopausal patients were collected from King Fahd Hospital, Saudi Arabia. Results: Computer assisted morphometric measurements of the vascular count, microvascular density and vascular area ratio were significantly enhanced in hyperplastic and neoplastic lesions as compared to normal breast specimens. Also, significant differences were observed in these vascular parameters between the three grades of invasive ductal carcinomas with the highest parameters in grade III. No significant differences were detected in the vascular parameters between premenopausal and postmenopausal cancer patients. Estrogen receptor expression was less in premenopausal as compared to postmenopausal women. No correlation was detected between the vascular parameters and the hormonal receptor expressions in normal breast tissues; or in different grades of malignancy. Conclusions: The computerized image analysis morphometric measurements of the results established several parameters in normal breast that can be beneficially used as a base for characterizing angiogenesis in breast carcinomas. By this way, a data base necessary for understanding when normal cells become malignant can be applied. Keywords: Microvascularization, hormonal receptors, computerized image analysis, breast tissue.
be due to a lower cytochrome activity and a higher glutathione peroxidase activity. We suggest that the higher UCP2 and UCP5 protein levels are involved in this lower oxidative stress. Keywords: Mammary carcinomas, oxidative stress, UCPs.
194 TRANSDUCTION SIGNALING PATHWAYS IN ESTROGEN RECEPTOR-POSITIVE/NEGATIVE MAMMARY CARCINOMAS J. Sastre-Serra 1 , M. Company 2 , A. Valle 1 , P. Roca 1 , G. Catalán 2 , J. Oliver 1 . 1 Grup de Metabolisme Energètic i Nutrició, Dpt. de Biologia Fonamental i Ciències de la Salut, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, and CIBERobn (CB06/03), Instituto de Salud Carlos III, Palma, Spain; 2 Hospital Son Llàtzer, Palma, Spain Reactive oxygen species (ROS) are intermediate cell metabolism products which not only act inside cells producing damage to lipids, proteins and nucleic acids, but whose levels can fluctuate in response to extracellular and intracellular signals too, working as second messengers in specific signalling cascades - like MAPKs (mitogen-activated protein kinases) involved in the cell process of differentiation, proliferation and apoptosis. Objectives: To compare activation state of these signalling cascades induced by oxidative stress in infiltrating ductal mammary carcinomas, positive or negative to estrogen receptors (ER+ and ER-). Methods: Twelve tumours (six of each group) were homogenized. Parameters of oxidative damage were analysed. AKT, SAPK/JNK, STAT3, ERK1/2 protein levels and phosphorylation state were determined. The ratio of phosphorylated protein versus total protein was also determined. Results: Oxidative stress was lower in ER+ tumours with respect to ER-. However, AKT, p-SAPK/JNK, p-ERK2 and ERK2 proteins levels were higher in ER- tumours. Phosphorylation ratios of SAPK/JNK, STAT3 and ERK1 with respect to their total protein levels were higher in ER-. Conclusions: The lower activation of oxidative stress-modulated signalling pathways by lower phosphorylation of proteins is a consequence of the lower oxidative stress observed in ER+ tumours. We suggest that this lower activation could be due to a higher activity of antioxidant enzymes such as glutathione peroxidase, and higher UCP2 and UCP5 protein levels in ER+ tumours. Keywords: Mammary carcinomas, oxidative stress, oxidative stressmodulated signalling pathways.
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195
STUDY OF REDOX STATE IN ESTROGEN RECEPTOR-POSITIVE/NEGATIVE MAMMARY CARCINOMAS
PHENOMENOLOGICAL STUDY OF PHANTOM BREAST SYNDROME
J. Sastre-Serra 1 , M. García-Bonafé 2 , J. Oliver 1 , G. Catalán 2 , P. Roca 1 . 1 Grup de Metabolisme Energètic i Nutrició, Dpt. de Biologia Fonamental i Ciències de la Salut, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, and CIBERobn (CB06/03), Instituto de Salud Carlos III, Palma, Spain; 2 Hospital Son Llàtzer, Palma, Spain
A. Spyropoulou 1 , C. Markopoulos 2, I. Zervas 1 , G. Christodoulou 3 , C. Papageorgiou 3 . 1 Women’s Mental Health Clinic, Eginition Hospital, First Department of Psychiatry, University of Athens, Athens, Greece; 2 Breast Unit, Laiko General Hospital, Second Department of Propedeutic Surgery, University of Athens, Athens, Greece; 3 Eginition Hospital, First Department of Psychiatry, University of Athens, Athens, Greece
Reactive oxygen species (ROS) are cell metabolism products which not only cause damage to cell structure, but also play a significant role in several chronic pathologies, like cancer. Estrogens are important mitogenic signals in breast cancer, regulating the expression of antioxidant enzymes and decreasing ROS production. Oxidative stress is the imbalance between ROS production and their removal by enzymatic and non-enzymatic antioxidant systems, with UCPs playing a possible key role as antioxidants. Objectives: To investigate the effects of estrogens on oxidative stress in infiltrating ductal mammary carcinomas, positive or negative to estrogen receptors (ER+ and ER-). Methods: Twelve tumours (six of each group) were homogenized. Parameters of oxidative damage as well as mtDNA content were assayed. Mitochondrial cytochrome c oxidase, Mn-superoxide dismutase, Cu/Znsuperoxide dismutase and glutathione peroxidase activities were also measured. Cytochrome c oxidase subunit IV and also UCP2 and UCP5 protein levels were determined. Results: Oxidative damage in proteins, cytochrome c oxidase activity and protein levels were higher in ER- with respect to ER+ tumours. The mtDNA content was similar in both types of tumours. Glutathione peroxidase activity, but not superoxide dismutase, and UCP2 and UCP5 protein levels were lower in ER- tumours. Conclusions: The lower oxidative damage in ER+ with respect to ER- could
Objectives: To better understand the phenomenology of phantom breast syndrome, which represents the experience of the continued presence of the breast after mastectomy and to look at its clinical relevance to phantom limb phenomena. Methods: One hundred and five (105) patients who had undergone mastectomy for non-metastatic breast cancer were interviewed by means of a structured questionnaire. Results: The group of women who experienced phantom breast syndrome consisted of 24 women (22.9%) with a mean age of 56.4 years (SD=10.5 years) Phantom pain was experienced by 6 patients (25%), who concurrently had other type of sensations, such as “itching” and “pinpricks”, at the phantom breast. In the majority of cases phantom experience had the size (88.9%), shape (76.5%) and weight (64.7%) of the normal breast and was localized in the entire breast (50%). Phantom sensations were rather indifferent for 65.3% of PBS patients, pleasant for 13.0% and unpleasant for 21.7%. Conclusions: PBS seems to represent a non disturbing phenomenon which usually is localized over the entire breast and is felt to have the qualities of a normal breast. Features such as prevalence, clinical relevance and localization seem to give PBS distinct characteristics in comparison to what is known about phantom limb. These differences could be partially attributed to the small representation of the breast in the somatosensory cortex and the absence of kinesthesis.