- Full Professor of Histology, pathologist, researcheredit
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... 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...
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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... 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.
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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... 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...
Research Interests: Aging, Atherosclerosis, Humans, Male, Risk factors, and 3 moreClinical Sciences, Aged, and Risk Factors
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... 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.
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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... 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.
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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... 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.
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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.... 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...
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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... 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...
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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... 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...
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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... 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...
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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... 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...
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Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using... more
Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological
behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted
against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study
included 50 pituitary adenoma cases. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method.
Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin
(STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone
(FSH), and luteinising hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The
percentage of Ki-67 positive nuclei (Ki-67 labeling index) was determined by counting approximately 1000 nuclei of the tumor cells at 400-fold
magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable
in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them
being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides
the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting
adenomas).
behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted
against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study
included 50 pituitary adenoma cases. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method.
Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin
(STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone
(FSH), and luteinising hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The
percentage of Ki-67 positive nuclei (Ki-67 labeling index) was determined by counting approximately 1000 nuclei of the tumor cells at 400-fold
magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable
in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them
being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides
the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting
adenomas).
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Purpose. Epidermal growth factor receptor (EGFR, HER1) and human epidermal receptor 2 (HER2) assessement in pituitary adenomas related to hormone profile. Design and methods. For 60 retrospective cases of pituitary adenomas, we... more
Purpose. Epidermal growth factor receptor (EGFR, HER1) and human epidermal receptor 2 (HER2) assessement in pituitary adenomas
related to hormone profile. Design and methods. For 60 retrospective cases of pituitary adenomas, we established the histopathologic
diagnosis by using morphological stains, followed by case selection for immunoprofile and EGFR and HER 2 assessement. Results.
More than one third of the studied pituitary adenomas (33,33%) were positive for HER2, with membranar pattern in basophilic cells
and with predominantly cytoplasmic, granular pattern for acidophils cells. HER2 immuno-expression characterized PRL secreting
adenomas (p=0.005) and associations between FSH-LH (p< 0.001) TSH-FSH (p=0,024) and TSH-LH (p=0.028). In situ hybridization
confirmed HER2 gene amplification in 33,34% out of all positive cases for HER2 by immunohistochemistry. EGFR positivity was found
significantly for GH-prolactin (p=0.000) and prolactin-ACTH (p=0.045) co-expressing pituitary adenomas, peritumoral macrophages
and folliculostellate cells. Conclusions. Differential HER2 and EGFR expression related to hormone profile heterogeneity can define
different subclasses of pituitary adenomas and could explain clinical, prognostic and therapeutic heterogeneity which are observed
in clinical practice. Our results support re-classification of pituitary adenomas based on molecular approach which should include
markers with well certified prognostic and therapeutic impact.
related to hormone profile. Design and methods. For 60 retrospective cases of pituitary adenomas, we established the histopathologic
diagnosis by using morphological stains, followed by case selection for immunoprofile and EGFR and HER 2 assessement. Results.
More than one third of the studied pituitary adenomas (33,33%) were positive for HER2, with membranar pattern in basophilic cells
and with predominantly cytoplasmic, granular pattern for acidophils cells. HER2 immuno-expression characterized PRL secreting
adenomas (p=0.005) and associations between FSH-LH (p< 0.001) TSH-FSH (p=0,024) and TSH-LH (p=0.028). In situ hybridization
confirmed HER2 gene amplification in 33,34% out of all positive cases for HER2 by immunohistochemistry. EGFR positivity was found
significantly for GH-prolactin (p=0.000) and prolactin-ACTH (p=0.045) co-expressing pituitary adenomas, peritumoral macrophages
and folliculostellate cells. Conclusions. Differential HER2 and EGFR expression related to hormone profile heterogeneity can define
different subclasses of pituitary adenomas and could explain clinical, prognostic and therapeutic heterogeneity which are observed
in clinical practice. Our results support re-classification of pituitary adenomas based on molecular approach which should include
markers with well certified prognostic and therapeutic impact.
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VEGF (vascular endothelial growth factor) and the receptor for VEGF- Flk-1 (fetal liver kinase 1) are important players of normal and pathologic angiogenesis. Also, it was proved that they are involved in tumor progression and metastasis... more
VEGF (vascular endothelial growth factor) and the receptor for VEGF- Flk-1 (fetal liver kinase 1) are important players of normal and pathologic angiogenesis. Also, it was proved that they are involved in tumor progression and metastasis in many tumors types by overexpression in cancer cells. Liver malignances and premalignant lesions represent controversial issues concerning VEGF and VEGFR2 (vascular endothelial growth factor receptor 2) expression and their potential involvement in the progression of inflammatory and cirrhotic lesions and also in malignant transformation is virtually unknown. The aim of this work was to describe the differentiate expression and distribution of VEGF and VEGFR2 in chronic hepatitis and liver cirrhosis, and according to these findings to better characterize the molecular profiling of liver disease with malignant transformation potential. We investigated 20 cases with chronic hepatitis and cirrhosis on specimens taken during surgery. Immunohistochemistry was performed in all cases for VEGF, VEGFR2, and FVIII related antigen (Von Willebrand factor). We found significant correlation between HAI (histological activity index) value, VEGF and VEGFR2 expression and factor FVIII related antigen in central part of specimens with chronic hepatitis. Liver cirrhosis lacks this correlation. Our findings suggested that VEGF dependent angiogenesis is more active in chronic hepatitis in the center of the lesion compared with cirrhosis where MVD (microvessel density) is higher at the periphery of the nodules. We hypothesize that the involvement of VEGF and VEGFR2 complex in development of chronic hepatitis and liver cirrhosis could be considered for the use of anti VEGF antibodies as adjuvant therapy in early stages of these diseases.
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Objective. Breast cancer is a one of the most common cancers in females worldwide. Basal cytokeratin CK5 represent the marker of progenitors for glandular and myoepithelial lineages of mammary epithelium. During epithelial differentiation... more
Objective. Breast cancer is a one of the most common cancers in females worldwide. Basal cytokeratin CK5 represent the marker of progenitors for glandular and myoepithelial lineages of mammary epithelium. During epithelial differentiation there is a gradual decrease of CK5 expression. The purpose of this study was to compare the expression of basal cytokeratin CK5 vs hormone receptors, HER2, Ki67 and molecular subtypes immunohistochemically defined in the primary breast carcinoma of NST type and axillar lymph node metastasis. Material and Methods. We processed immunohistochemically 91 invasive breast carcinomas of NST type and their ipsilateral axillar lymph node metastasis (LNM). Results. The majority of primary tumors were evaluated as CK5 negative (78 cases/85.7%). The majority of cases were evaluated as Luminal B (50 cases/54.9%) and Luminal A (28 cases/30.8%) tumors. The HER2 subtype was confirmed in 8 cases/8.8%, 5NP in 3 cases/3.3% and Basal-like in 2 cases/2.2%. The parallel comparison of CK5 expression at both sites, primary and metastatic, revealed that this marker is not stable during metastatic progression. The molecular subtypes were not stable during metastatic process in 21 cases/23.1%. Conclusions. The majority of NST invasive ductal breast carcinomas are CK5 negative. The molecular subtypes and CK5 are not stable during metastatic process. Cancerous cells prefer to lose this marker in the lymph node environment. The presence of cases with simultaneous expression of CK5 and hormone receptors is an open field to debate the existence of other, transient molecular subtypes. We expect a further confirmation in larger study groups.
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Otolaryngology is mainly associated with clinical practice. Despite of this actual evidence, otolaryngology can be considered, from historical point of view as a complex speciality made up of a mixture of several preclinical specialities... more
Otolaryngology is mainly associated with clinical practice. Despite of this actual evidence, otolaryngology can be considered, from historical point of view as a complex speciality made up of a mixture of several preclinical specialities as anatomy, histology, pathology and physiology. Several scientists who studied these specialities first, became then otolaryngologists and others were known in the medical literature because of their studies in other specialities than otolaryngology. Most of the historical papers were focused on the ear, other regions being neglected. This review presents the forgotten part of otolaryngology, especially its preclinical facts with importance in etiology and pathogenesis of various disease of the ear, nose and throat structures and thus, present work can be considered as a particular overview of „forgotten” otolaryngology.
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Rare and inconsistent data are reported for chorioallantoic tumor models of renal cell carcinoma and none of them has used endostatin as an inhibitory agent of tumor development. We aimed to perform a comparative analysis of tumor cells... more
Rare and inconsistent data are reported for chorioallantoic tumor models of renal cell carcinoma and none of them has used endostatin as an inhibitory agent of tumor development. We aimed to perform a comparative analysis of tumor cells and blood vessels from renal cell carcinoma on endostatin-treated and non-treated chorioallantoic membrane (CAM) implants by the assessment of endoglin, vascular endothelial growth factor (VEGF) and smooth muscle actin expression. Endostatin triple action on tumor, endothelial and perivascular cells was observed in the present study. Differential impact of endostatin treatment on intratumor and peritumor blood vessels was noticed on the VEGF expression and behaviour of tumor cells between clear cell and papillary components of RCC. Based on our findings, a high tumor heterogenity response to endostatin has been highlighted. Interplay between VEGF, endoglin and endostatin in RCC could support a combined targeted therapy to improve prognosis of patient...
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Molecular classifications of several malignancies are already accepted and applied in clinical practice. For head and neck squamous cell carcinomas (HNSCCs) there exist few and controversial data regarding their stratification on distinct... more
Molecular classifications of several malignancies are already accepted and applied in clinical practice. For head and neck squamous cell carcinomas (HNSCCs) there exist few and controversial data regarding their stratification on distinct groups or sub-groups and thus, none of them are validated as useful tools for diagnosis and therapy. Starting from the highly expressed markers in HNSCC (epidermal growth factor receptor, keratin 5 and E cadherin) we proposed to identify distinct HNSCC sub-groups with a potential impact on prognosis and therapy. Complex analysis of immunohistochemical expression for six surrogate markers (EGFR, p53, Bcl2, CD117, keratin 5 and E-cadherin) defined three distinct sub-classes amongst EGFR-positive cases, based on the association and differential expression of p53 and Bcl2 (EGFR(+)/p53(-)/bcl2(-), EGFR(+)/p53(+)/bcl2(-) and EGFR(+)/p53(+)/bcl2(+)). Amongst them, only the EGFR(+)/p53+/bcl2(-) sub-class showed significant correlations with grade and TNM p...
The purpose of this study is to evaluate the value of cytokeratin (CK) MNF116 and vimentin in the differential diagnosis of malignant pleural effusions. There were evaluated smears from 30 patients with pleural effusions stained with... more
The purpose of this study is to evaluate the value of cytokeratin (CK) MNF116 and vimentin in the differential diagnosis of malignant pleural effusions. There were evaluated smears from 30 patients with pleural effusions stained with May-Grünwald Giemsa and Papanicolaou techniques for the routine cytological diagnosis. Additional smears were immunostained with CK MNF116 and vimentin using LSAB2 technique. Two independent observers evaluated all smears. Smears were classified first by cytological examination in seven cases (23.33%) as benign, and in 23 cases (76.67%) as malignant pleural effusions. Mesothelial cells expressed CK MNF116 in 96.67% (29/30) of cases and vimentin in 33.33% (10/30) of cases. Malignant cells expressed CK MNF116 in 52.17% (12/23) of cases and vimentin in 30.43% (7/23) of cases. The pattern of immunostaining was diffuse cytoplasmic. In conclusion, CK MNF116 and vimentin may be used as a part of the panel of antibodies for differential diagnosis of malignant pleural effusions with primary unknown.
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Prox1 is a key regulator of lymphatic endothelial cell commitment during embryonic development. No correlations between Prox1 and VEGF-C/VEGFR3 expression in cervical cancer has been done until now. The aim of the present study was to... more
Prox1 is a key regulator of lymphatic endothelial cell commitment during embryonic development. No correlations between Prox1 and VEGF-C/VEGFR3 expression in cervical cancer has been done until now. The aim of the present study was to evaluate the peculiarities of Prox1, VEGF-C and VEGFR3 expression during uterine cervix neoplasia progression. Material and methods. One hundred and four specimens taken from women with macroscopically detectable lesions were classified by histopathology and analyzed by immunohistochemistry for Prox1, VEGFR3 and VEGF-C expression. Results. The presence of Prox1 nuclear expression was detected starting from CIN2 and CIN3 lesions to microinvasive carcinoma, in the nuclei of lymphatic and venous endothelial cells and scattered stromal cells. All Prox1 positive lymphatic vessels were positive for VEGFR3. A significant correlation was found between expression of VEGF-C in tumor cells and nuclear density of Prox1 positive lymphatic cells (p=0.044). Conclusion. The commitment of Prox1 positive cells through a lymphatic lineage is an early event for cervical neoplastic progression, being present starting with intraepithelial cervical lesions, and is strongly associated with VEGFR3 and VEGF-C expression. These findings suggest an early active lymphangiogenesis during cervical neoplasia progression and explain, in part, the early presence of lymph node metastasis in cervical cancer. By the detection of Prox1 expression in lymphatic and venous endothelial cells, and also in stromal cells, it has been suggested that there are at least three different mechanism of lymph vessel development during cervical neoplasia progression.
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Aim: To investigate a possible correlation between the histological and morphometric properties of herniated intervertebral disc, clinical and magnetic resonance imaging (MRI) characteristics of patients with lumbar disc degeneration... more
Aim: To investigate a possible correlation between the histological and morphometric properties of herniated intervertebral disc, clinical and magnetic resonance imaging (MRI) characteristics of patients with lumbar disc degeneration (LDD). Materials and Methods: Thirty six patients with LDD were clinically evaluated using Japanese Orthopaedic Association Score (JOAS), visual analogue scale (VAS) for pain in the lower back or in the pelvic limb; MRI-based classification according to Pfirrmann and Modic criteria. All patients underwent decompressive surgery and herniated intervertebral disc samples were histologically and morphometrically analyzed. Data obtained were statistically analyzed for bivariate and partial correlations. Results: The mean area size of chondron clusters correlated with age, JOAS (r=-0.385, p=0.032, tau=-0.279, rho=-0.380), Pfirrmann (r=0.505, p=0.002, tau=0.289, rho=0.365) and Modic (r=0.500, p=0.002, tau=0.331, rho=0.419) grading. There was a strong correlation between maximum area size of chondrons and JOAS (r=-0.427, p=0.009, tau=-0.299, rho=-0.430), Pfirrmann changes (r=0.432, p=0.008, tau=0.309, rho=0.388) and Modic endplate changes (r=0.444, p=0.007, tau=0.343, rho=0.434). JOAS correlated with both MRI classifications used for LDD. Conclusion: The intervertebral disc cells tend to aggregate in clusters and the size of the chondrons from LDD correlated with JOAS, Pfirrmann and Modic. JOAS correlates with the imagistic evaluation systems Pfirrmann and Modic.
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Several papers about lymphangiogenesis and inflammation focused on the detailed and complicated descriptions of the molecular pathways accompanying both non-tumor and tumor inflammatory-induced lymphatic vessel development. Many authors... more
Several papers about lymphangiogenesis and inflammation focused on the detailed and complicated descriptions of the molecular pathways accompanying both non-tumor and tumor inflammatory-induced lymphatic vessel development. Many authors are tempted to present inflammatory-induced lymphangiogenesis in pathologic conditions neglecting the role of inflammatory cells during embryonic lymphatic vessel development. Some of the inflammatory cells are largely characterized in inflammatory-induced lymphangiogenesis, while others as mast cells, eosinophils, or plasma cells are less studied. No phenotypic characterization of inflammation-activated lymphatic endothelial cell is available in this moment. Another paradox is related to the existence of few papers regarding lymphangiogenesis inside lymphoid organs and for their related pathology. There are still several &amp;amp;amp;amp;quot;missing pieces of such a big puzzle&amp;amp;amp;amp;quot; of lymphangiogenesis and inflammation, with a direct impact on the ineffectiveness of the anti-inflammatory therapy as lymphangiogenesis inhibitors. The present paper will focus on the controversial issues of lymphangiogenesis and inflammation.
In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal... more
In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.
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Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study... more
Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on ...
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E-Cadherin is a marker with a controversial function. Its role is often interpreted in the context of the epithelial-mesenchymal transition. In ambiguous cases, it is used as a phenotypic marker of lobular subtype of breast carcinoma. It... more
E-Cadherin is a marker with a controversial function. Its role is often interpreted in the context of the epithelial-mesenchymal transition. In ambiguous cases, it is used as a phenotypic marker of lobular subtype of breast carcinoma. It has been well-studied in primary cancer, but its expression after metastasis is not well-described. The aim of this study was to determine the evolution of E-cadherin expression in no special type (NST) primary breast carcinoma and to correlate this with that in distant, paired nodal metastases (LNM) and molecular classification. We processed 88 invasive breast carcinomas of NST type and their paired LNM. The specimens were formalin-fixed and paraffin embedded. Sections were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), basal cytokeratin CK5, nuclear protein Ki67 and E-cadherin with a Leica Bond-Max autostainer. The results obtained were grouped into four molecular subtypes: Lu...