The presence and distribution of lymphatic vessels and mast cells in the gingiva under normal and... more The presence and distribution of lymphatic vessels and mast cells in the gingiva under normal and pathological conditions have been reported by several studies, but the relationship between them during inflammatory lymphangiogenesis is virtually unknown. The aim of the present study was to investigate the lymphatic microvessel density (LMVD) and mast cell density (MCD) in the gingiva of patients with periodontal disease compared to normal-like gingiva. Gingival punch biopsies from 51 patients with periodontal disease were investigated. MCs and LVs were detected by double-immunohistochemistry, using primary antibodies against mast cell tryptase and D2-40. The inflammatory infiltrate was evaluated on a scale from 0 (absent) to +3 (severe inflammation). MCs and LVs were counted in the same microscopic field for each case at ×200 magnification. We found a significant increase in the number of both MCs and LVs in cases with mild and moderate inflammatory changes, followed by a slight dec...
Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formati... more Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types.
The formation of new blood vessels, or angiogenesis, is a complex process that plays important ro... more The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the... more Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the most common method used for evaluation of angiogenesis, it has several limitations. Our aim was to evaluate MVD and microvessel proliferation (MVP) in a series of invasive breast carcinomas and analyze whether angiogenesis is influenced by the molecular phenotype of each tumor. We examined vascular proliferation using double immunohistochemistry (CD34/Ki67) in a series of 54 invasive breast carcinomas and compared the results with standard MVD, molecular subtypes and other classical parameters. Increased MVD and MVP values were recorded in basal-like subtype, but only the MVP value reached significance among this group of patients (p=0.0001). For all cases combined, increased MVP was significantly correlated with negative estrogen receptor (ER) status (p=0.010) and higher histological grade (p=0.002). MVP more accurately reflects the state of angiogenesis in breast cancer, compared with...
The true onset of atherosclerosis remains one of the biggest challenges for cardiologists. Is ath... more The true onset of atherosclerosis remains one of the biggest challenges for cardiologists. Is atheroma plaque development considered the earliest step of vascular aging? If so, when it starts? Before or after birth? If it starts before birth or early during childhood, it seems that Thomas Sydenham was right: "A man is as old as his arteries." Except disorganization of elastic fibers, less is known about the morphology of vascular aging and also about the molecular events influencing the age of arteries, arterial stiffness, and their role in the appearance of future complications. Cellular and molecular events responsible for the switch from physiologic to pathologic aging of human arteries are less known. Epigenetic, genetic, and environmental influences at the onset of early vascular aging (EVA) should specifically influence the process. This paper briefly reviews the controversial data regarding vascular aging with an emphasis on the less known facts about the morphology of EVA.
Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory... more Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory reaction occurring at the periphery of the tumor. Mast cell-secreted angiogenic cytokines facilitate tumor vascularization not only by a direct effect but also by stimulating other inflammatory cells of the tumor microenvironment to release other angiogenic mediators. An increased number of mast cells have been demonstrated in angiogenesis associated with solid tumors, including breast cancer. Mast cells might act as a new target for the adjuvant treatment of breast cancer through the selective inhibition of angiogenesis, tissue remodeling and tumor promoting molecules, allowing the secretion of cytotoxic cytokines and preventing mast cell mediated immune-suppression.
One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are crit... more One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are critically overviewed here, being focused on data useful in clinical practice or to improve the therapy and patients survival. TNBCs "choose" young women and its "kiss" is, unfortunately deadly in most cases. Currently, few sparse data are available in literature concerning the origins of TNBC. Vasculogenic mimicry detected in TNBCs, seems to be determined by a population of CD133+ cells and may be stimulated by different pharmacological agents such sunitinib. Despite the fact that TNBCs do not usually metastasize through the lymphatic pathways, TNBCs may be characterized by lymphatic invasion and by an increased lymphatic microvascular density. If TNBCs treatment depends on the molecular profile of the tumor, the same statement may be postulated for TNBCs metastasis. Whether metastases have a similar phenotype as the primary tumor remains an enigma. Therefore, the question: 'Could TNBC be subject to a standardized, unanimously accepted therapeutic strategy or is it strictly subclass-dependent?' remains to be further investigated.
Based on these evidence, we sought to validate the cytoplasmic expression of PROX1 in normal and ... more Based on these evidence, we sought to validate the cytoplasmic expression of PROX1 in normal and tumor gastric mucosa as a true or false expression and also to find out if the PROX1 expression and amplification could have a clinical impact for patients with gastric cancer.
Angiogenesis is an essential process involved in the normal growth and differentiation. In its de... more Angiogenesis is an essential process involved in the normal growth and differentiation. In its defective and excessive form, angiogenesis is a crucial event in the progression of many human diseases. Excessive angiogenesis was largely investigated in psoriasis, arthritis, diabetic retinopathy and malignant tumours. Soon after the discovery of angiogenic factors and their inhibitors, the angiogenesis jumped from the experimental studies to clinical application. Tumour-associated angiogenesis is nowadays considered as a priority in oncology based on numerous evidences that showed a significant reduction in tumour growth following anti-angiogenic therapy. However, few data are available on pre-malignant conditions. First evidences on angiogenesis in pre-malignant lesions came from the evaluation of microvessel density (MVD). MVD was found to be significantly increased in a relatively large spectrum of pre-malignant squamous cell lesions, such as in the oral mucosa, skin, uterine cervix, vulva and anal canal. For many of them, a correlation was found between MVD and the expression of vascular endothelial growth factor (VEGF). Based on these data, it was suggested that tumour angiogenesis is not necessarily a characteristic of invasive tumour, but may be an early event during tumourigenesis. Additional evidences came from pre-malignant lesions of glandular epithelia, in which the angiogenic switch was demonstrated by the immunohistochemical expression of VEGF in gastric metaplasia and dysplasia, in atypical adenoma of the colon, atypical hyperplasia and carcinoma in situ of the breast and others. Actually, there are convincing evidences for an active angiogenesis in many cases with pre-malignant conditions, and this supports a more accurate evaluation of different chemopreventive agents.
Tumor metastasis represents a major problem in the treatment of patients with different cancers. ... more Tumor metastasis represents a major problem in the treatment of patients with different cancers. Specific phenotype and behavior of metastatic cells derive from specific molecular mechanisms involved in consecutive steps of the metastatic process. Several in vitro and in vivo experimental models have been utilized, but they cannot completely reproduce and characterize each step of the metastatic process. This review article is focused on the chick embryo chorioallantoic membrane as an in vivo model to study the metastatic process.
Romanian Journal of Morphology and Embryology Revue Roumaine De Morphologie Et Embryologie, Feb 1, 2005
Purpose: Our aim was to investigate the distribution of CD34 and smooth muscle cell actin positiv... more Purpose: Our aim was to investigate the distribution of CD34 and smooth muscle cell actin positive myofibroblasts in the stroma of the normal mammary gland, benign and malignant tumors. The observations were especially focused on the diagnostic value of the cumulative results obtained with these immunoreactions. Methods: Our study included 112 female patients with suspect breast masses obtained by surgery or biopsy. We performed morphological study and immunohistochemistry for CD34 and SMA. Results: We have found normal breast tissue, sclerosing adenosis, fibroadenomas, fibrocystic diseases, phyllodes tumor, DCIS, ductal invasive, lobular, squamous, medullary, mucinous, and papillary carcinomas. We also found apocrine metaplasia, florid ductal hyperplasia, atypical hyperplasia, papilloma and LCIS associated with the malignant tumors. All the normal breast tissues and most of benign lesions were positive for CD34 and negative for SMA. The exceptions were represented by a case of fibroadenoma and the phyllodes tumor, with CD34 positivity and a focal acquisition of SMA; fibrocystic disease with associated apocrine metaplasia adjacent to a squamous carcinoma with loss of CD34 expression and focal acquisition of SMA. All our DCIS and invasive carcinomas have lost CD34 expression and gained SMA positivity. Some particular behavior had the mucinous and squamous carcinomas. Conclusions: Although there were some exceptions especially when one of the two markers was interpreted separately and in some cases associated with sclerotic stroma, we conclude that the combined expression of CD34 and a-SMA is of potential diagnostic value in the distinction between benign and malignant tumors in some difficult cases.
The aim of the study was to compare the simple immunostains performed with CD31, CD34 and CD105 a... more The aim of the study was to compare the simple immunostains performed with CD31, CD34 and CD105 antibodies, with double-labeling immunostains realized with CD105 (endoglin) and smooth muscle actin antibodies in colorectal carcinomas. Fourty colorectal carcinoma surgical specimens were immunohistochemically studied. Quantification of microvessel density was realized at 400× magnification, in the intratumoral and peritumoral areas and distant from the tumor. With simple immunostains, it was very difficult to identify the type of vessel. With CD105/smooth muscle actin double-labeling stain we determined vessels maturation grade and identified the following types of vessels: isolated endothelial cells, immature, intermediary, mature and activated mature vessels. The density of intermediate vessels was higher in well-differentiated (2 ± 0.03) than in moderately (0.14 ± 0,02) or poorly differentiated colorectal carcinoma (0.07 ± 0.01). Such vessel types could not be identified with simple...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2009
Breast cancer is a heterogeneous disease that includes several molecular types, characterized by ... more Breast cancer is a heterogeneous disease that includes several molecular types, characterized by the expression profile of sex hormone receptors, HER2 protein, cytokeratin 5, p53, and Bcl-2. EGFR is an additional marker predominantly expressed by basal-like carcinoma, but its significance in the other types is not completely understood. The aim of this study was to analyze the immunohistochemical expression of EGFR and its relationships with other factors of prognosis. There were investigated benign lesions and 84 cases with invasive breast carcinoma that were submitted first to the molecular classification. Next, we performed the staining for EGFR and two patterns of the final product of reaction were described. EGFR expression was found in 41.66% of the cases with basal-like carcinoma, in 50% of the cases with luminal B carcinoma, and in 21.42% of the cases with HER2 overexpression. A significant correlation was found between EGFR expression and degree of differentiation and dista...
In the last decade, much data has been generated concerning the molecular mechanisms of lymphangi... more In the last decade, much data has been generated concerning the molecular mechanisms of lymphangiogenesis and its significance in pathological conditions. This was mainly due to the discovery of lymphatic endothelial cell (LEC)-specific markers, such as vascular endothelial growth factor receptor-3 (VEGFR-3), LYVE-1, Prox-1 and podoplanin. Podoplanin, originally detected on the surface of podocytes, belongs to the family of type-1 transmembrane sialomucin-like glycoproteins. Although specific for lymphatic vascular (LV) endothelium, podoplanin is expressed in a wide variety of normal and tumor cells. The expression of podoplanin is induced by the homeobox gene Prox-1 and a specific endogenous receptor was identified on platelets. Immunohistochemical detection of podoplanin/D2-40 in LECs was used in many studies to evaluate the LV microvascular density (LVMD) in peritumoral and tumoral areas, and to correlate LVMD with lymph node status and prognosis. Podoplanin significantly increas...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2007
Systemic sclerosis or scleroderma is a rare collagen disease, characterized by insufficient angio... more Systemic sclerosis or scleroderma is a rare collagen disease, characterized by insufficient angiogenesis. Few data are available about the morphologic and histochemical peculiarities of the skin in these patients with this condition. The purpose of the present work was to evaluate the histochemical aspects of sclerodermic skin, obtained through biopsy of the typical lesions from the forearm skin. The study was conducted on 31 patients, from which skin biopsies were obtained, after informed consent. The specimens were fixed in buffer formalin, embedded in paraffin and processed for staining with HE, Masson, orcein, Gordon-Sweet silver staining, and alcian blue-safranin, in order to identify elastic fibers, reticular fibers, glycosaminoglycans and mast cells. Results are partially similar to other studies: the constant depletion of elastic fibers in the papillary dermis and disorders of the network in the reticular dermis, such as their absence in the skin blood vessels walls. The ret...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2007
To compare the angiogenesis in anal canal carcinomas (ACC) with that in colorectal carcinomas (CR... more To compare the angiogenesis in anal canal carcinomas (ACC) with that in colorectal carcinomas (CRC). A number of 507 CRC, surgical specimens, were analyzed, 12 cases (1.97%) being ACC. In 20 cases from left and right colon (CRC) and in the 12 ACC we analyzed the immunohistochemical parameters related to angiogenesis, utilizing the following LabVision antibodies: CD31, CD105 (endoglin) and VEGF1. Morphometrical analysis and positive cell counting were performed in the tumoral and peritumoral tissue. Immunoperoxidase method was used. The average age was 63.17 +/- 10.87 years in CRC, respectively 57.9 +/- 10.05 years in the ACC (p<0.0001). Compared with CRC the ACC occur more frequently at the females (58%). Angiogenesis was expressed in the majority of cases. In CRC, the microvascular density (MVD) was higher than that from ACC. The ratio CD31/CD105 was 1 in ACC and 3 in CRC. VEGF was positive in 25% of ACC and 80% of CRC. In CRC were more mature vessels, marked only with CD31 than...
Themolecularphenotypicheterogeneityofmastcells(MCs)makesthemattractive aspotentialtherapeutictarg... more Themolecularphenotypicheterogeneityofmastcells(MCs)makesthemattractive aspotentialtherapeutictargetsinanti-canceradjuvanttherapy.Mastcellaggregationsobservedintumorssuggestedtheirinvolvementintumorpathogenesis.Despiteseveralstudiesusingmastcelltryptase,MCs'involvementintheprogression ofprostatetumorshasnotbeendemonstrated.Theaimofourstudywastoidentify andquantifythephenotypicheterogeneityofMCsinprostatelesions.Ourstudy included7casesofnormalprostate,25casesofbenignepithelialhyperplasiaand 64casesofprostatecarcinoma.MCswereimmunohistochemicallyassessedusing three markers: tryptase, chymase and CD117. Two immunophenotypes of MCs were identified in benign lesions: tryptase+/CD117+/chymase-and tryptase-/ chymase+/CD117+,locatedinperitumoralareas.IntratumoralMCphenotypeof malignantlesionswascharacterizedbytryptase+/chymase+/CD117+,whilein theperitumoralareasthreedifferentMCsphenotypeswereidentified:tryptase+/ chymase+/CD117-, tryptase+/CD117+/chymase-and chymase+/CD117+/ tryptase-.OurresultssuggestthecorrelationofchymasepositiveMCsoftheperitumoral areas and CD117 positive MCs of the intratumoral areas with tumor grade.
Childhood dermal tumors with melanocytic features is an unusual tumor that can create diagnostic ... more Childhood dermal tumors with melanocytic features is an unusual tumor that can create diagnostic confusion. Among them, paraganglioma-like melanocytic tumors-previous included in melanocytic tumors of uncertain malignant potential-has some particular histopathologic and immunohistochemical features. We describe a case of 13 years old girl with a paraganglioma-like dermal melanocytic tumor of the left leg.
The presence and distribution of lymphatic vessels and mast cells in the gingiva under normal and... more The presence and distribution of lymphatic vessels and mast cells in the gingiva under normal and pathological conditions have been reported by several studies, but the relationship between them during inflammatory lymphangiogenesis is virtually unknown. The aim of the present study was to investigate the lymphatic microvessel density (LMVD) and mast cell density (MCD) in the gingiva of patients with periodontal disease compared to normal-like gingiva. Gingival punch biopsies from 51 patients with periodontal disease were investigated. MCs and LVs were detected by double-immunohistochemistry, using primary antibodies against mast cell tryptase and D2-40. The inflammatory infiltrate was evaluated on a scale from 0 (absent) to +3 (severe inflammation). MCs and LVs were counted in the same microscopic field for each case at ×200 magnification. We found a significant increase in the number of both MCs and LVs in cases with mild and moderate inflammatory changes, followed by a slight dec...
Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formati... more Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types.
The formation of new blood vessels, or angiogenesis, is a complex process that plays important ro... more The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the... more Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the most common method used for evaluation of angiogenesis, it has several limitations. Our aim was to evaluate MVD and microvessel proliferation (MVP) in a series of invasive breast carcinomas and analyze whether angiogenesis is influenced by the molecular phenotype of each tumor. We examined vascular proliferation using double immunohistochemistry (CD34/Ki67) in a series of 54 invasive breast carcinomas and compared the results with standard MVD, molecular subtypes and other classical parameters. Increased MVD and MVP values were recorded in basal-like subtype, but only the MVP value reached significance among this group of patients (p=0.0001). For all cases combined, increased MVP was significantly correlated with negative estrogen receptor (ER) status (p=0.010) and higher histological grade (p=0.002). MVP more accurately reflects the state of angiogenesis in breast cancer, compared with...
The true onset of atherosclerosis remains one of the biggest challenges for cardiologists. Is ath... more The true onset of atherosclerosis remains one of the biggest challenges for cardiologists. Is atheroma plaque development considered the earliest step of vascular aging? If so, when it starts? Before or after birth? If it starts before birth or early during childhood, it seems that Thomas Sydenham was right: "A man is as old as his arteries." Except disorganization of elastic fibers, less is known about the morphology of vascular aging and also about the molecular events influencing the age of arteries, arterial stiffness, and their role in the appearance of future complications. Cellular and molecular events responsible for the switch from physiologic to pathologic aging of human arteries are less known. Epigenetic, genetic, and environmental influences at the onset of early vascular aging (EVA) should specifically influence the process. This paper briefly reviews the controversial data regarding vascular aging with an emphasis on the less known facts about the morphology of EVA.
Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory... more Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory reaction occurring at the periphery of the tumor. Mast cell-secreted angiogenic cytokines facilitate tumor vascularization not only by a direct effect but also by stimulating other inflammatory cells of the tumor microenvironment to release other angiogenic mediators. An increased number of mast cells have been demonstrated in angiogenesis associated with solid tumors, including breast cancer. Mast cells might act as a new target for the adjuvant treatment of breast cancer through the selective inhibition of angiogenesis, tissue remodeling and tumor promoting molecules, allowing the secretion of cytotoxic cytokines and preventing mast cell mediated immune-suppression.
One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are crit... more One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are critically overviewed here, being focused on data useful in clinical practice or to improve the therapy and patients survival. TNBCs "choose" young women and its "kiss" is, unfortunately deadly in most cases. Currently, few sparse data are available in literature concerning the origins of TNBC. Vasculogenic mimicry detected in TNBCs, seems to be determined by a population of CD133+ cells and may be stimulated by different pharmacological agents such sunitinib. Despite the fact that TNBCs do not usually metastasize through the lymphatic pathways, TNBCs may be characterized by lymphatic invasion and by an increased lymphatic microvascular density. If TNBCs treatment depends on the molecular profile of the tumor, the same statement may be postulated for TNBCs metastasis. Whether metastases have a similar phenotype as the primary tumor remains an enigma. Therefore, the question: 'Could TNBC be subject to a standardized, unanimously accepted therapeutic strategy or is it strictly subclass-dependent?' remains to be further investigated.
Based on these evidence, we sought to validate the cytoplasmic expression of PROX1 in normal and ... more Based on these evidence, we sought to validate the cytoplasmic expression of PROX1 in normal and tumor gastric mucosa as a true or false expression and also to find out if the PROX1 expression and amplification could have a clinical impact for patients with gastric cancer.
Angiogenesis is an essential process involved in the normal growth and differentiation. In its de... more Angiogenesis is an essential process involved in the normal growth and differentiation. In its defective and excessive form, angiogenesis is a crucial event in the progression of many human diseases. Excessive angiogenesis was largely investigated in psoriasis, arthritis, diabetic retinopathy and malignant tumours. Soon after the discovery of angiogenic factors and their inhibitors, the angiogenesis jumped from the experimental studies to clinical application. Tumour-associated angiogenesis is nowadays considered as a priority in oncology based on numerous evidences that showed a significant reduction in tumour growth following anti-angiogenic therapy. However, few data are available on pre-malignant conditions. First evidences on angiogenesis in pre-malignant lesions came from the evaluation of microvessel density (MVD). MVD was found to be significantly increased in a relatively large spectrum of pre-malignant squamous cell lesions, such as in the oral mucosa, skin, uterine cervix, vulva and anal canal. For many of them, a correlation was found between MVD and the expression of vascular endothelial growth factor (VEGF). Based on these data, it was suggested that tumour angiogenesis is not necessarily a characteristic of invasive tumour, but may be an early event during tumourigenesis. Additional evidences came from pre-malignant lesions of glandular epithelia, in which the angiogenic switch was demonstrated by the immunohistochemical expression of VEGF in gastric metaplasia and dysplasia, in atypical adenoma of the colon, atypical hyperplasia and carcinoma in situ of the breast and others. Actually, there are convincing evidences for an active angiogenesis in many cases with pre-malignant conditions, and this supports a more accurate evaluation of different chemopreventive agents.
Tumor metastasis represents a major problem in the treatment of patients with different cancers. ... more Tumor metastasis represents a major problem in the treatment of patients with different cancers. Specific phenotype and behavior of metastatic cells derive from specific molecular mechanisms involved in consecutive steps of the metastatic process. Several in vitro and in vivo experimental models have been utilized, but they cannot completely reproduce and characterize each step of the metastatic process. This review article is focused on the chick embryo chorioallantoic membrane as an in vivo model to study the metastatic process.
Romanian Journal of Morphology and Embryology Revue Roumaine De Morphologie Et Embryologie, Feb 1, 2005
Purpose: Our aim was to investigate the distribution of CD34 and smooth muscle cell actin positiv... more Purpose: Our aim was to investigate the distribution of CD34 and smooth muscle cell actin positive myofibroblasts in the stroma of the normal mammary gland, benign and malignant tumors. The observations were especially focused on the diagnostic value of the cumulative results obtained with these immunoreactions. Methods: Our study included 112 female patients with suspect breast masses obtained by surgery or biopsy. We performed morphological study and immunohistochemistry for CD34 and SMA. Results: We have found normal breast tissue, sclerosing adenosis, fibroadenomas, fibrocystic diseases, phyllodes tumor, DCIS, ductal invasive, lobular, squamous, medullary, mucinous, and papillary carcinomas. We also found apocrine metaplasia, florid ductal hyperplasia, atypical hyperplasia, papilloma and LCIS associated with the malignant tumors. All the normal breast tissues and most of benign lesions were positive for CD34 and negative for SMA. The exceptions were represented by a case of fibroadenoma and the phyllodes tumor, with CD34 positivity and a focal acquisition of SMA; fibrocystic disease with associated apocrine metaplasia adjacent to a squamous carcinoma with loss of CD34 expression and focal acquisition of SMA. All our DCIS and invasive carcinomas have lost CD34 expression and gained SMA positivity. Some particular behavior had the mucinous and squamous carcinomas. Conclusions: Although there were some exceptions especially when one of the two markers was interpreted separately and in some cases associated with sclerotic stroma, we conclude that the combined expression of CD34 and a-SMA is of potential diagnostic value in the distinction between benign and malignant tumors in some difficult cases.
The aim of the study was to compare the simple immunostains performed with CD31, CD34 and CD105 a... more The aim of the study was to compare the simple immunostains performed with CD31, CD34 and CD105 antibodies, with double-labeling immunostains realized with CD105 (endoglin) and smooth muscle actin antibodies in colorectal carcinomas. Fourty colorectal carcinoma surgical specimens were immunohistochemically studied. Quantification of microvessel density was realized at 400× magnification, in the intratumoral and peritumoral areas and distant from the tumor. With simple immunostains, it was very difficult to identify the type of vessel. With CD105/smooth muscle actin double-labeling stain we determined vessels maturation grade and identified the following types of vessels: isolated endothelial cells, immature, intermediary, mature and activated mature vessels. The density of intermediate vessels was higher in well-differentiated (2 ± 0.03) than in moderately (0.14 ± 0,02) or poorly differentiated colorectal carcinoma (0.07 ± 0.01). Such vessel types could not be identified with simple...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2009
Breast cancer is a heterogeneous disease that includes several molecular types, characterized by ... more Breast cancer is a heterogeneous disease that includes several molecular types, characterized by the expression profile of sex hormone receptors, HER2 protein, cytokeratin 5, p53, and Bcl-2. EGFR is an additional marker predominantly expressed by basal-like carcinoma, but its significance in the other types is not completely understood. The aim of this study was to analyze the immunohistochemical expression of EGFR and its relationships with other factors of prognosis. There were investigated benign lesions and 84 cases with invasive breast carcinoma that were submitted first to the molecular classification. Next, we performed the staining for EGFR and two patterns of the final product of reaction were described. EGFR expression was found in 41.66% of the cases with basal-like carcinoma, in 50% of the cases with luminal B carcinoma, and in 21.42% of the cases with HER2 overexpression. A significant correlation was found between EGFR expression and degree of differentiation and dista...
In the last decade, much data has been generated concerning the molecular mechanisms of lymphangi... more In the last decade, much data has been generated concerning the molecular mechanisms of lymphangiogenesis and its significance in pathological conditions. This was mainly due to the discovery of lymphatic endothelial cell (LEC)-specific markers, such as vascular endothelial growth factor receptor-3 (VEGFR-3), LYVE-1, Prox-1 and podoplanin. Podoplanin, originally detected on the surface of podocytes, belongs to the family of type-1 transmembrane sialomucin-like glycoproteins. Although specific for lymphatic vascular (LV) endothelium, podoplanin is expressed in a wide variety of normal and tumor cells. The expression of podoplanin is induced by the homeobox gene Prox-1 and a specific endogenous receptor was identified on platelets. Immunohistochemical detection of podoplanin/D2-40 in LECs was used in many studies to evaluate the LV microvascular density (LVMD) in peritumoral and tumoral areas, and to correlate LVMD with lymph node status and prognosis. Podoplanin significantly increas...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2007
Systemic sclerosis or scleroderma is a rare collagen disease, characterized by insufficient angio... more Systemic sclerosis or scleroderma is a rare collagen disease, characterized by insufficient angiogenesis. Few data are available about the morphologic and histochemical peculiarities of the skin in these patients with this condition. The purpose of the present work was to evaluate the histochemical aspects of sclerodermic skin, obtained through biopsy of the typical lesions from the forearm skin. The study was conducted on 31 patients, from which skin biopsies were obtained, after informed consent. The specimens were fixed in buffer formalin, embedded in paraffin and processed for staining with HE, Masson, orcein, Gordon-Sweet silver staining, and alcian blue-safranin, in order to identify elastic fibers, reticular fibers, glycosaminoglycans and mast cells. Results are partially similar to other studies: the constant depletion of elastic fibers in the papillary dermis and disorders of the network in the reticular dermis, such as their absence in the skin blood vessels walls. The ret...
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2007
To compare the angiogenesis in anal canal carcinomas (ACC) with that in colorectal carcinomas (CR... more To compare the angiogenesis in anal canal carcinomas (ACC) with that in colorectal carcinomas (CRC). A number of 507 CRC, surgical specimens, were analyzed, 12 cases (1.97%) being ACC. In 20 cases from left and right colon (CRC) and in the 12 ACC we analyzed the immunohistochemical parameters related to angiogenesis, utilizing the following LabVision antibodies: CD31, CD105 (endoglin) and VEGF1. Morphometrical analysis and positive cell counting were performed in the tumoral and peritumoral tissue. Immunoperoxidase method was used. The average age was 63.17 +/- 10.87 years in CRC, respectively 57.9 +/- 10.05 years in the ACC (p<0.0001). Compared with CRC the ACC occur more frequently at the females (58%). Angiogenesis was expressed in the majority of cases. In CRC, the microvascular density (MVD) was higher than that from ACC. The ratio CD31/CD105 was 1 in ACC and 3 in CRC. VEGF was positive in 25% of ACC and 80% of CRC. In CRC were more mature vessels, marked only with CD31 than...
Themolecularphenotypicheterogeneityofmastcells(MCs)makesthemattractive aspotentialtherapeutictarg... more Themolecularphenotypicheterogeneityofmastcells(MCs)makesthemattractive aspotentialtherapeutictargetsinanti-canceradjuvanttherapy.Mastcellaggregationsobservedintumorssuggestedtheirinvolvementintumorpathogenesis.Despiteseveralstudiesusingmastcelltryptase,MCs'involvementintheprogression ofprostatetumorshasnotbeendemonstrated.Theaimofourstudywastoidentify andquantifythephenotypicheterogeneityofMCsinprostatelesions.Ourstudy included7casesofnormalprostate,25casesofbenignepithelialhyperplasiaand 64casesofprostatecarcinoma.MCswereimmunohistochemicallyassessedusing three markers: tryptase, chymase and CD117. Two immunophenotypes of MCs were identified in benign lesions: tryptase+/CD117+/chymase-and tryptase-/ chymase+/CD117+,locatedinperitumoralareas.IntratumoralMCphenotypeof malignantlesionswascharacterizedbytryptase+/chymase+/CD117+,whilein theperitumoralareasthreedifferentMCsphenotypeswereidentified:tryptase+/ chymase+/CD117-, tryptase+/CD117+/chymase-and chymase+/CD117+/ tryptase-.OurresultssuggestthecorrelationofchymasepositiveMCsoftheperitumoral areas and CD117 positive MCs of the intratumoral areas with tumor grade.
Childhood dermal tumors with melanocytic features is an unusual tumor that can create diagnostic ... more Childhood dermal tumors with melanocytic features is an unusual tumor that can create diagnostic confusion. Among them, paraganglioma-like melanocytic tumors-previous included in melanocytic tumors of uncertain malignant potential-has some particular histopathologic and immunohistochemical features. We describe a case of 13 years old girl with a paraganglioma-like dermal melanocytic tumor of the left leg.
a m Registration, Senate Hall, 1 st floor 9 : 0 0 a m -9 : 1 0 a m Histology Museum Open, 3 rd fl... more a m Registration, Senate Hall, 1 st floor 9 : 0 0 a m -9 : 1 0 a m Histology Museum Open, 3 rd floor, Histology Department Opening Ceremony (Senate Hall, 1 st floor) Keynote Address: Prof. Marius Raica 9 : 1 0 a m -1 0 : 3 0 a m KEYNOTE LECTURES (Senate Hall, 1 st floor) Chairs: Marius Raica, Domenico Ribatti, Irina Draga Căruntu 9.10-9.30: Synchrotron Microbeam Radiation -a novel and potent angiodisruptive strategy Valentin Djonov, Bern, Switzerland 9.30-9.50: The role of Bcl6/p53, inflammatory cells infiltration and angiogenesis in invasive breast carcinoma story about breast cancerprimary tumor as prince charming and synchronous lymph node metastasis as Cinderella 1 0 : 3 0 a m -1 1 : 0 0 a m Coffee Break, 3 rd floor, Histology Department 1 1 : 0 0 a m -1 : 0 0 p m KEYNOTE LECTURES
Objective: Currently there are two major types of antiviral therapy in HBV chronic liver disease:... more Objective: Currently there are two major types of antiviral therapy in HBV chronic liver disease: PegInterferon alpha-2a and nucleoside/ nucleotide agents. The aim of this study was to evaluate the response to PegInterferon alfa-2a treatment, in patients with chronic hepatitis B.
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Papers by Anca Cimpean