El-Hassan Shabana - Academia.edu (original) (raw)

Papers by El-Hassan Shabana

Research paper thumbnail of Characterization of cytokeratin patterns in the developing human tongue

The International Journal of Developmental Biology

The characterization of cytokeratin (CK) in adult oral mucosa and developing teeth have been well... more The characterization of cytokeratin (CK) in adult oral mucosa and developing teeth have been well documented in human. Cytokeratin distribution in developing oral mucosa has not yet been described. The aim of this study was to identify the expression of CK in human fetal tongue (week 10 to week 23) and to correlate the results with morphological maturation. Simple epithelial CK are expressed in all cell layers during the early stages, essentially in peridermal cells. From the 14th week, CK 18 is present only in the taste buds, making this polypeptide a reliable marker for this sensory organ. CK 4 and 13 are expressed from the 10th to the 23rd week by both ventral and dorsal lingual epithelia. Terminal differentiation keratins (CK 1, 2 and 10-11) can only be detected immunohistochemically at the 14th week in some cells on the external surface of some papillae. The number of these papillae and positive cells increase at the 19th and 23rd weeks. The terminal differentiation markers are expressed several weeks earlier than the formation of a well-distinguished keratinized layer.

Research paper thumbnail of Cytokeratins as markers of cell differentiation: expression in normal epithelia

Pathologie Biologie

ABSTRACT

Research paper thumbnail of A switch in cytokeratin expression and intermediate filament organization associated with epithelial stratification

Journal de biologie buccale

Low density gingival epithelial cells were cultured on the side of glass slides facing rat&#3... more Low density gingival epithelial cells were cultured on the side of glass slides facing rat's tail collagen lattices. Under these conditions and in the presence of physiological level of calcium, colony formation was enhanced and stratification was slowed down. The strong attachment of the cells to glass slides permitted immunocytochemical examination of cytokeratin (CK) expression and their organization within individual cells during the different stages of epithelial maturation. The present results showed that during the stage of cell migration and colony formation, the cells express the same set of cytokeratins (basal cell marker 14, simple epithelial markers 8, 18 and 19, and marker of hyperproliferation 16) which forms a well-defined network of organized filaments. At the stratification stage, the filament network became dense by the additional expression of the markers of differentiation in non-keratinized stratified epithelia (CK 4 and 13). These appeared once individual cells started to overlap the basal cells, a period during which the cell-temporarily changed morphology. Whilst the suprabasal cells exhibited dense filament network labelled for CK 4 and 13, the density of labelled filaments for CK 14, 8 and 18 was much lower, indicating that these cells contained newly-formed filaments lacking the basal and simple epithelial keratins. The simple epithelial cytokeratins became weakly labelled in older cultures. The uncoupling of paired expression of cytokeratins 4 and 13 was observed in non-colony forming aged cells. This provides an example of altered program of cytokeratin expression during epithelial maturation.

Research paper thumbnail of Expression du gène Msx2 dans les papillomes inversés

Research paper thumbnail of Molecules desmosomiales

Research paper thumbnail of Papagerakis P, Pannone G, Shabana EH, Depondt J, Santoro A, Ghirtis K, Berdal A, Papagerakis S.Aberrant bêta -catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer.Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):135-46

Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin... more Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and...

Research paper thumbnail of P.92 Wnt signaling in oropharynx squamous cell carcinoma

Oral Oncology Supplement, 2005

massive hemorrhage, although an CT-investigation at this time detected no sign of intracerebral l... more massive hemorrhage, although an CT-investigation at this time detected no sign of intracerebral lymphoma invasion. Conclusion: The clinical picture of a high malignant lymphoma can be determined first by intraoral findings which are valuable for the hlstopathologlcal diagnosas. According to the classification and tile chmcal stage a conlbined therapy could be reconmlended. Generally speaking the treatment is considerably less successful compared to other system diseases like morbus Hodgkm.

Research paper thumbnail of Aberrant beta-catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer

International journal of immunopathology and pharmacology

Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin... more Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and...

Research paper thumbnail of Altered plakoglobin expression at mRNA and protein levels correlates with clinical outcome in patients with oropharynx squamous carcinomas

Human pathology, 2004

Previous studies have established that expression of plakoglobin is down-regulated during maligna... more Previous studies have established that expression of plakoglobin is down-regulated during malignant transformation. The aim of this study was to evaluate for the first time the expression of plakoglobin at the mRNA and protein levels in primary oropharyngeal squamous cell carcinomas (SCCs) and determine the extent to which the patterns of expression correlated with clinical parameters. Plakoglobin expression was evaluated in 37 new tumor cases and normal oral epithelium using immunofluorescence, reverse transcriptase-polymerase chain reaction (RT-PCR), and Northern and Western blotting analysis. The results indicated that the steady-state levels of plakoglobin protein were down-regulated in all tumors compared with normal epithelium. Furthermore, in 87.1% of the tumors, plakoglobin immunoreactivity displayed an abnormal cytoplasmic localization that was inversely correlated with tumor size and directly correlated with a poor clinical outcome for the patient. Northern blotting analys...

Research paper thumbnail of Cytoplasmic desmosome formation by H-7 and EGF treatment in cultured fetal rat keratinocytes

Tissue & cell, 1996

Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many epithelial tumors... more Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many epithelial tumors. Their significance and mechanism of formation remain largely speculative. Recently, we have reported the induction of these structures in rat keratinocytes following a brief treatment with acrylamide, and proposed that protein kinase inhibition may be implicated in their formation. In the present study, we show that protein kinase inhibitor H-7 in the presence of EGF is able to induce CD in rat keratinocytes within half an hour. In serum free medium containing 20 ng/ml of EGF, desmosomal structures at different stages of assembly were obtained using H-7 at concentrations ranging between 20 and 80 microM. No such structures were found at lower concentrations. The plaque diameters were significantly small in comparison with plasma membrane plaques. EGF induced plakoglobin positive membrane invaginations and in the presence of H-7, desmosomal plaques assembled on these membranes as either...

Research paper thumbnail of Expression of the CA1 determinant by carcinomas and by non-malignant epithelial cells in oral lesions

British journal of cancer, 1983

The expression of the Ca antigen was investigated in 5 groups of oral lesions comprising 7 squamo... more The expression of the Ca antigen was investigated in 5 groups of oral lesions comprising 7 squamous cell carcinomas, 2 pre-invasive carcinomas, 7 lesions of types believed to predispose to carcinoma, 19 lesions of types that do not predispose to carcinoma and 5 biopsies of normal oral mucosa. Using an indirect immunoperoxidase method, the neoplastic epithelium reacted positively with the Ca1 antibody in only 4 out of 7 oral squamous cell carcinomas and the reaction varied between the specimens as to the intensity and number of positively stained cells. Several benign oral lesions specifically bound the Ca1 antibody in areas of epithelium showing infiltration with inflammatory cells. These lesions comprised 5 fibrous epulides, 1 pyogenic granuloma, 1 denture-induced hyperplasia and 1 non-diagnostic ulcer. We conclude that the Ca1 antibody is not sufficiently specific for the carcinoma to be of value in the diagnosis of malignant and premalignant lesions of the oral mucosa.

Research paper thumbnail of Expression of blood group H antigen by normal, benign, and carcinoma cells of the oral epithelium: immunohistochemical study using monoclonal antibody RS13

Oral surgery, oral medicine, and oral pathology, 1986

The H antigen was investigated by an indirect immunoperoxidase method in sections of 65 surgical ... more The H antigen was investigated by an indirect immunoperoxidase method in sections of 65 surgical specimens from the oral mucosa. These comprised 29 squamous cell carcinomas, 28 benign lesions, and 8 specimens of clinically healthy mucosa. A monoclonal antibody (RS13) was used to identify the H antigen. The peroxidase stain was positive at high dilutions of the antibody in the epithelium of normal mucosa, and the titers were significantly higher than those within benign lesions (p less than 0.001) and carcinomas (p less than 0.001). However, the titers in the benign lesions varied considerably, with two specimens recorded as negative. In contrast, the reaction for the H antigen was negative in 19 specimens (66%) of the malignant lesions and the endpoint titers of the H positive carcinomas indicated marked loss of the antigen. This loss was significant when compared to the benign lesions (p less than 0.001). The results show that the loss of the H antigen on malignant epithelial cells...

Research paper thumbnail of Expression of blood group H antigen type 2 chain by oral carcinoma cells after radiotherapy

Oral surgery, oral medicine, and oral pathology, 1987

The blood group H antigen type 2 was investigated immunohistochemically in sections of 44 surgica... more The blood group H antigen type 2 was investigated immunohistochemically in sections of 44 surgical specimens from the oral mucosa. These comprised 35 squamous cell carcinomas obtained from 22 patients and 9 specimens of clinically healthy mucosa. The carcinoma specimens included 10 primary lesions and 25 recurrent lesions from patients who had undergone radiotherapy. The results showed that the specimens of normal oral mucosa stained at higher antibody titers than either group of carcinomas, and that postradiation recurrent tumors stained at higher titers than primary tumors. In 10 patients, both preradiation and postradiation carcinomas were examined; the postradiation lesions showed increased reactivity in 5 patients, no change in 3 patients, and a decrease in antigen reactivity in 2 patients. The expression of antigen H type 2 in the recurrent tumors appeared to correlate with the estimated daily tumor radiation dose; tumors with specific antigen staining took twice as long to re...

Research paper thumbnail of Cytokeratin expression in human tongue epithelium

American Journal of Anatomy, 1990

The epithelium of the human tongue shows diverse morphological variations from one site to anothe... more The epithelium of the human tongue shows diverse morphological variations from one site to another and even within the epithelium of the same papilla. This complexity has led to confusion regarding tongue epithelium as being orthokeratinized, parakeratinized, or nonkeratinized. Cytokeratins have been shown to characterize different epithelia. The present paper describes cytokeratin expression by adult tongue epithelia and relates their distribution to morphology. Six healthy human tongue specimens were obtained after plastic surgery and cytokeratin expression was investigated immunohistochemically, using a panel of 15 antibodies for cytoskeletal proteins, and biochemically using two-dimensional gel electrophoresis. The results showed that the ventral and lateral surfaces of the tongue are related to the nonkeratinizing stratified squamous epithelia, esophageal type, whereas the dorsal surface showed mixed expression of cytokeratins. In the tip of filiform and on the surface of fungiform papillae, cytokeratins of terminal differentiation are expressed as skin type; and in the rest of the papillae as well as in interpapillary areas, the epithelium expresses esophageal type cytokeratins. Certain simple epithelial cytokeratins were found in taste buds. Cytokeratin 19 was also detected in the basal cell layer of all esophageal type epithelia in the tongue. The present results provide basis for studies on the biological events in epithelial differentiation during development and in pathology.

Research paper thumbnail of Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

Human Pathology, 2009

Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Downregulat... more Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Downregulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.

Research paper thumbnail of Nasal inverted papilloma expresses the muscle segment homeobox gene Msx2: possible prognostic implications

Human Pathology, 2008

Nasal inverted papilloma is a rare benign tumor of epithelial origin with aggressive evolution, b... more Nasal inverted papilloma is a rare benign tumor of epithelial origin with aggressive evolution, bone destruction, recurrence, and malignant transformation. Msx2 is a homeobox gene implicated in organ development, bone metabolism, and tumorigenesis. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry, Msx2 expression was examined in nasal inverted papilloma and in nontumorigenic tissue counterparts. For the first time, Msx2 was detected in all inverted papillomas but not in the nasal polyps or in the normal mucosa. The protein expression level was directly and significantly associated with tumor recurrence. Furthermore, Msx2 was associated with bone resorption markers receptor activator of nuclear factor-kappa B ligand and tartrate-resistant acid phosphatase, suggesting a role in osteolysis. In conclusion, Msx2 expression may represent a useful prognostic marker in inverted papilloma.

Research paper thumbnail of Cytoplasmic desmosomes and intermediate filament disturbance following acrylamide treatment in cultured rat keratinocytes

Tissue and Cell, 1994

The present paper describes disturbances in the organization of tonofilaments and desmosomes of r... more The present paper describes disturbances in the organization of tonofilaments and desmosomes of rat lingual and epidermal keratinocytes after treatment of the cells with acrylamide in culture. This treatment induced changes in cell shape, reduction of intercellular adhesion and a perinuclear accumulation of cytoplasmic organelles. Using specific antibodies for cytokeratins, the filaments were disorganized particularly in the perinuclear region. In untreated cells, keratin filament labelling was very weak or absent above and below the nucleus thus leaving a black nuclear space in fluorescine microscopy. Following acrylamide treatment, the keratin filament labelling covered the nuclear space which indicated the accumulation of these filaments all around the nucleus. Furthermore, the desmosomal junctions were often associated with thick keratin bundles. Antibodies for desmoplakins revealed a reduction in intercellular labelling and stronger cytoplasmic labelling. Ultrastructurally, well-developed long tonofilaments were found to associate with large desmosomal junctions. Furthermore. smallsized desmosomal structures were identified within the cytoplasm. Morphologically, these were identical to cell surface desmosomes and were almost always associated with well-developed tonofilaments. The effect of acrylamide on the protein kinase A activity might be implicated in the disturbances of the desmosome-intermediate filament complex and in the initiation of contractile forces necessary for pexinuclear accumulation of intermediate filaments and for the formation of intact cytoplasmic desmosomes. The acrylamide-induced intermediate filament and desmosomal changes may provide valuable information on the mechanism of intact cytoplasmic desmosome formation in several skin diseases and in squamous cell carcinoma.

Research paper thumbnail of Changes in cytokeratin expression in gingiva during inflammation

Journal of Periodontal Research, 1990

Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The pu... more Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The purpose of this study was to describe the alterations of cytokeratin pattern and topographical distribution of individual cytokeratins in inflamed gingiva. Five healthy and 15 inflammatory samples of human gingiva were studied. From each biopsy, cryostat sections allowed histological staining, immunofluorescence microscopy using a battery of monoclonal antibodies to cytokeratins, and gel electrophoresis. The results show marked differences in cytokeratin expression by healthy epithelia as compared with inflamed gingiva: in suprabasal cell layers there were reductions or disappearance of cytokeratins 1, 2 and 10, 11--specific for terminal differentiation--and increased expression of cytokeratins 4 and 13, as well as--in basal and parabasal cell layers--expression of cytokeratin 19. These alterations might represent an adaptation of involved epithelia to the alterations brought about by the inflammatory process.

Research paper thumbnail of Infiltrating (intramuscular) benign lipoma of the head and neck

Journal of Oral and Maxillofacial Surgery, 1991

Research paper thumbnail of Histological evaluation of natural coral skeleton as a grafting material in miniature swine mandible

Journal of Materials Science: Materials in Medicine, 1992

Natural coral skeleton (NCS) has recently been proposed as a bone graft substitute that enhances ... more Natural coral skeleton (NCS) has recently been proposed as a bone graft substitute that enhances bone formation. The present paper describes the effects of implanting NCS in bone cavities prepared in the mandibles of miniature pig, and compares these with the effects of two alloplastic materials; a tricalcium phosphate (TCP) and a porous hydroxyapatite (PHA). On 11 pigs, 5 ×

Research paper thumbnail of Characterization of cytokeratin patterns in the developing human tongue

The International Journal of Developmental Biology

The characterization of cytokeratin (CK) in adult oral mucosa and developing teeth have been well... more The characterization of cytokeratin (CK) in adult oral mucosa and developing teeth have been well documented in human. Cytokeratin distribution in developing oral mucosa has not yet been described. The aim of this study was to identify the expression of CK in human fetal tongue (week 10 to week 23) and to correlate the results with morphological maturation. Simple epithelial CK are expressed in all cell layers during the early stages, essentially in peridermal cells. From the 14th week, CK 18 is present only in the taste buds, making this polypeptide a reliable marker for this sensory organ. CK 4 and 13 are expressed from the 10th to the 23rd week by both ventral and dorsal lingual epithelia. Terminal differentiation keratins (CK 1, 2 and 10-11) can only be detected immunohistochemically at the 14th week in some cells on the external surface of some papillae. The number of these papillae and positive cells increase at the 19th and 23rd weeks. The terminal differentiation markers are expressed several weeks earlier than the formation of a well-distinguished keratinized layer.

Research paper thumbnail of Cytokeratins as markers of cell differentiation: expression in normal epithelia

Pathologie Biologie

ABSTRACT

Research paper thumbnail of A switch in cytokeratin expression and intermediate filament organization associated with epithelial stratification

Journal de biologie buccale

Low density gingival epithelial cells were cultured on the side of glass slides facing rat&#3... more Low density gingival epithelial cells were cultured on the side of glass slides facing rat's tail collagen lattices. Under these conditions and in the presence of physiological level of calcium, colony formation was enhanced and stratification was slowed down. The strong attachment of the cells to glass slides permitted immunocytochemical examination of cytokeratin (CK) expression and their organization within individual cells during the different stages of epithelial maturation. The present results showed that during the stage of cell migration and colony formation, the cells express the same set of cytokeratins (basal cell marker 14, simple epithelial markers 8, 18 and 19, and marker of hyperproliferation 16) which forms a well-defined network of organized filaments. At the stratification stage, the filament network became dense by the additional expression of the markers of differentiation in non-keratinized stratified epithelia (CK 4 and 13). These appeared once individual cells started to overlap the basal cells, a period during which the cell-temporarily changed morphology. Whilst the suprabasal cells exhibited dense filament network labelled for CK 4 and 13, the density of labelled filaments for CK 14, 8 and 18 was much lower, indicating that these cells contained newly-formed filaments lacking the basal and simple epithelial keratins. The simple epithelial cytokeratins became weakly labelled in older cultures. The uncoupling of paired expression of cytokeratins 4 and 13 was observed in non-colony forming aged cells. This provides an example of altered program of cytokeratin expression during epithelial maturation.

Research paper thumbnail of Expression du gène Msx2 dans les papillomes inversés

Research paper thumbnail of Molecules desmosomiales

Research paper thumbnail of Papagerakis P, Pannone G, Shabana EH, Depondt J, Santoro A, Ghirtis K, Berdal A, Papagerakis S.Aberrant bêta -catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer.Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):135-46

Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin... more Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and...

Research paper thumbnail of P.92 Wnt signaling in oropharynx squamous cell carcinoma

Oral Oncology Supplement, 2005

massive hemorrhage, although an CT-investigation at this time detected no sign of intracerebral l... more massive hemorrhage, although an CT-investigation at this time detected no sign of intracerebral lymphoma invasion. Conclusion: The clinical picture of a high malignant lymphoma can be determined first by intraoral findings which are valuable for the hlstopathologlcal diagnosas. According to the classification and tile chmcal stage a conlbined therapy could be reconmlended. Generally speaking the treatment is considerably less successful compared to other system diseases like morbus Hodgkm.

Research paper thumbnail of Aberrant beta-catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer

International journal of immunopathology and pharmacology

Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin... more Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and...

Research paper thumbnail of Altered plakoglobin expression at mRNA and protein levels correlates with clinical outcome in patients with oropharynx squamous carcinomas

Human pathology, 2004

Previous studies have established that expression of plakoglobin is down-regulated during maligna... more Previous studies have established that expression of plakoglobin is down-regulated during malignant transformation. The aim of this study was to evaluate for the first time the expression of plakoglobin at the mRNA and protein levels in primary oropharyngeal squamous cell carcinomas (SCCs) and determine the extent to which the patterns of expression correlated with clinical parameters. Plakoglobin expression was evaluated in 37 new tumor cases and normal oral epithelium using immunofluorescence, reverse transcriptase-polymerase chain reaction (RT-PCR), and Northern and Western blotting analysis. The results indicated that the steady-state levels of plakoglobin protein were down-regulated in all tumors compared with normal epithelium. Furthermore, in 87.1% of the tumors, plakoglobin immunoreactivity displayed an abnormal cytoplasmic localization that was inversely correlated with tumor size and directly correlated with a poor clinical outcome for the patient. Northern blotting analys...

Research paper thumbnail of Cytoplasmic desmosome formation by H-7 and EGF treatment in cultured fetal rat keratinocytes

Tissue & cell, 1996

Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many epithelial tumors... more Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many epithelial tumors. Their significance and mechanism of formation remain largely speculative. Recently, we have reported the induction of these structures in rat keratinocytes following a brief treatment with acrylamide, and proposed that protein kinase inhibition may be implicated in their formation. In the present study, we show that protein kinase inhibitor H-7 in the presence of EGF is able to induce CD in rat keratinocytes within half an hour. In serum free medium containing 20 ng/ml of EGF, desmosomal structures at different stages of assembly were obtained using H-7 at concentrations ranging between 20 and 80 microM. No such structures were found at lower concentrations. The plaque diameters were significantly small in comparison with plasma membrane plaques. EGF induced plakoglobin positive membrane invaginations and in the presence of H-7, desmosomal plaques assembled on these membranes as either...

Research paper thumbnail of Expression of the CA1 determinant by carcinomas and by non-malignant epithelial cells in oral lesions

British journal of cancer, 1983

The expression of the Ca antigen was investigated in 5 groups of oral lesions comprising 7 squamo... more The expression of the Ca antigen was investigated in 5 groups of oral lesions comprising 7 squamous cell carcinomas, 2 pre-invasive carcinomas, 7 lesions of types believed to predispose to carcinoma, 19 lesions of types that do not predispose to carcinoma and 5 biopsies of normal oral mucosa. Using an indirect immunoperoxidase method, the neoplastic epithelium reacted positively with the Ca1 antibody in only 4 out of 7 oral squamous cell carcinomas and the reaction varied between the specimens as to the intensity and number of positively stained cells. Several benign oral lesions specifically bound the Ca1 antibody in areas of epithelium showing infiltration with inflammatory cells. These lesions comprised 5 fibrous epulides, 1 pyogenic granuloma, 1 denture-induced hyperplasia and 1 non-diagnostic ulcer. We conclude that the Ca1 antibody is not sufficiently specific for the carcinoma to be of value in the diagnosis of malignant and premalignant lesions of the oral mucosa.

Research paper thumbnail of Expression of blood group H antigen by normal, benign, and carcinoma cells of the oral epithelium: immunohistochemical study using monoclonal antibody RS13

Oral surgery, oral medicine, and oral pathology, 1986

The H antigen was investigated by an indirect immunoperoxidase method in sections of 65 surgical ... more The H antigen was investigated by an indirect immunoperoxidase method in sections of 65 surgical specimens from the oral mucosa. These comprised 29 squamous cell carcinomas, 28 benign lesions, and 8 specimens of clinically healthy mucosa. A monoclonal antibody (RS13) was used to identify the H antigen. The peroxidase stain was positive at high dilutions of the antibody in the epithelium of normal mucosa, and the titers were significantly higher than those within benign lesions (p less than 0.001) and carcinomas (p less than 0.001). However, the titers in the benign lesions varied considerably, with two specimens recorded as negative. In contrast, the reaction for the H antigen was negative in 19 specimens (66%) of the malignant lesions and the endpoint titers of the H positive carcinomas indicated marked loss of the antigen. This loss was significant when compared to the benign lesions (p less than 0.001). The results show that the loss of the H antigen on malignant epithelial cells...

Research paper thumbnail of Expression of blood group H antigen type 2 chain by oral carcinoma cells after radiotherapy

Oral surgery, oral medicine, and oral pathology, 1987

The blood group H antigen type 2 was investigated immunohistochemically in sections of 44 surgica... more The blood group H antigen type 2 was investigated immunohistochemically in sections of 44 surgical specimens from the oral mucosa. These comprised 35 squamous cell carcinomas obtained from 22 patients and 9 specimens of clinically healthy mucosa. The carcinoma specimens included 10 primary lesions and 25 recurrent lesions from patients who had undergone radiotherapy. The results showed that the specimens of normal oral mucosa stained at higher antibody titers than either group of carcinomas, and that postradiation recurrent tumors stained at higher titers than primary tumors. In 10 patients, both preradiation and postradiation carcinomas were examined; the postradiation lesions showed increased reactivity in 5 patients, no change in 3 patients, and a decrease in antigen reactivity in 2 patients. The expression of antigen H type 2 in the recurrent tumors appeared to correlate with the estimated daily tumor radiation dose; tumors with specific antigen staining took twice as long to re...

Research paper thumbnail of Cytokeratin expression in human tongue epithelium

American Journal of Anatomy, 1990

The epithelium of the human tongue shows diverse morphological variations from one site to anothe... more The epithelium of the human tongue shows diverse morphological variations from one site to another and even within the epithelium of the same papilla. This complexity has led to confusion regarding tongue epithelium as being orthokeratinized, parakeratinized, or nonkeratinized. Cytokeratins have been shown to characterize different epithelia. The present paper describes cytokeratin expression by adult tongue epithelia and relates their distribution to morphology. Six healthy human tongue specimens were obtained after plastic surgery and cytokeratin expression was investigated immunohistochemically, using a panel of 15 antibodies for cytoskeletal proteins, and biochemically using two-dimensional gel electrophoresis. The results showed that the ventral and lateral surfaces of the tongue are related to the nonkeratinizing stratified squamous epithelia, esophageal type, whereas the dorsal surface showed mixed expression of cytokeratins. In the tip of filiform and on the surface of fungiform papillae, cytokeratins of terminal differentiation are expressed as skin type; and in the rest of the papillae as well as in interpapillary areas, the epithelium expresses esophageal type cytokeratins. Certain simple epithelial cytokeratins were found in taste buds. Cytokeratin 19 was also detected in the basal cell layer of all esophageal type epithelia in the tongue. The present results provide basis for studies on the biological events in epithelial differentiation during development and in pathology.

Research paper thumbnail of Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

Human Pathology, 2009

Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Downregulat... more Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Downregulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.

Research paper thumbnail of Nasal inverted papilloma expresses the muscle segment homeobox gene Msx2: possible prognostic implications

Human Pathology, 2008

Nasal inverted papilloma is a rare benign tumor of epithelial origin with aggressive evolution, b... more Nasal inverted papilloma is a rare benign tumor of epithelial origin with aggressive evolution, bone destruction, recurrence, and malignant transformation. Msx2 is a homeobox gene implicated in organ development, bone metabolism, and tumorigenesis. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry, Msx2 expression was examined in nasal inverted papilloma and in nontumorigenic tissue counterparts. For the first time, Msx2 was detected in all inverted papillomas but not in the nasal polyps or in the normal mucosa. The protein expression level was directly and significantly associated with tumor recurrence. Furthermore, Msx2 was associated with bone resorption markers receptor activator of nuclear factor-kappa B ligand and tartrate-resistant acid phosphatase, suggesting a role in osteolysis. In conclusion, Msx2 expression may represent a useful prognostic marker in inverted papilloma.

Research paper thumbnail of Cytoplasmic desmosomes and intermediate filament disturbance following acrylamide treatment in cultured rat keratinocytes

Tissue and Cell, 1994

The present paper describes disturbances in the organization of tonofilaments and desmosomes of r... more The present paper describes disturbances in the organization of tonofilaments and desmosomes of rat lingual and epidermal keratinocytes after treatment of the cells with acrylamide in culture. This treatment induced changes in cell shape, reduction of intercellular adhesion and a perinuclear accumulation of cytoplasmic organelles. Using specific antibodies for cytokeratins, the filaments were disorganized particularly in the perinuclear region. In untreated cells, keratin filament labelling was very weak or absent above and below the nucleus thus leaving a black nuclear space in fluorescine microscopy. Following acrylamide treatment, the keratin filament labelling covered the nuclear space which indicated the accumulation of these filaments all around the nucleus. Furthermore, the desmosomal junctions were often associated with thick keratin bundles. Antibodies for desmoplakins revealed a reduction in intercellular labelling and stronger cytoplasmic labelling. Ultrastructurally, well-developed long tonofilaments were found to associate with large desmosomal junctions. Furthermore. smallsized desmosomal structures were identified within the cytoplasm. Morphologically, these were identical to cell surface desmosomes and were almost always associated with well-developed tonofilaments. The effect of acrylamide on the protein kinase A activity might be implicated in the disturbances of the desmosome-intermediate filament complex and in the initiation of contractile forces necessary for pexinuclear accumulation of intermediate filaments and for the formation of intact cytoplasmic desmosomes. The acrylamide-induced intermediate filament and desmosomal changes may provide valuable information on the mechanism of intact cytoplasmic desmosome formation in several skin diseases and in squamous cell carcinoma.

Research paper thumbnail of Changes in cytokeratin expression in gingiva during inflammation

Journal of Periodontal Research, 1990

Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The pu... more Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The purpose of this study was to describe the alterations of cytokeratin pattern and topographical distribution of individual cytokeratins in inflamed gingiva. Five healthy and 15 inflammatory samples of human gingiva were studied. From each biopsy, cryostat sections allowed histological staining, immunofluorescence microscopy using a battery of monoclonal antibodies to cytokeratins, and gel electrophoresis. The results show marked differences in cytokeratin expression by healthy epithelia as compared with inflamed gingiva: in suprabasal cell layers there were reductions or disappearance of cytokeratins 1, 2 and 10, 11--specific for terminal differentiation--and increased expression of cytokeratins 4 and 13, as well as--in basal and parabasal cell layers--expression of cytokeratin 19. These alterations might represent an adaptation of involved epithelia to the alterations brought about by the inflammatory process.

Research paper thumbnail of Infiltrating (intramuscular) benign lipoma of the head and neck

Journal of Oral and Maxillofacial Surgery, 1991

Research paper thumbnail of Histological evaluation of natural coral skeleton as a grafting material in miniature swine mandible

Journal of Materials Science: Materials in Medicine, 1992

Natural coral skeleton (NCS) has recently been proposed as a bone graft substitute that enhances ... more Natural coral skeleton (NCS) has recently been proposed as a bone graft substitute that enhances bone formation. The present paper describes the effects of implanting NCS in bone cavities prepared in the mandibles of miniature pig, and compares these with the effects of two alloplastic materials; a tricalcium phosphate (TCP) and a porous hydroxyapatite (PHA). On 11 pigs, 5 ×