bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of E‐cadherin in oral cancer cell lines and its relationship to invasiveness in SCID mice in vivo
Authors: Hoteiya Toshiaki , Hayashi Eiji , Satomura Kazuhito , Kamata Nobouki , Nagayama Masaru
Published: August 2010

We examined the expression of E‐cadherin in nine oral cancer cell lines. HSC‐4, NA, ZA, HOC927 and Ca9–22 cells strongly expressed E‐cadherin [E‐CD(++) cell line] and HSC‐2 and HSC‐3 cells weakly expressed E‐cadherin [E‐CD(+) cell line]. All the cell lines that expressed E‐cadherin were of cuboidal morphology and formed cobblestone colonies. In contrast, TSU and HOC313 cells had spindle shapes, formed dispersed colonies, and were completely negative for E‐cadherin [E‐CD(‐) cell line]. Moreover, all cell lines that expressed E‐cadherin showed tumorgenicity in SCID mice, but E‐CD(‐) cell lines did not show tumorgenicity. The tumors derived from E‐CD(+) cell lines invaded deeper into the connective tissues than those from E‐CD(++) cell lines. In immunohistochemical analysis, the difference was more marked at the edges of the cancer nests. These results suggest that E‐cadherin expression was relevant to the cell forms and the differential grade of cultured cells and that reduced E‐cadherin in oral cancer may be associated with invasiveness in vivo.
Bilirubin pigmentation of human teeth caused by hyperbilirubinemia
Authors: Watanabe Kazufumi , Shibata Toshiyki , Kurosawa Takao , Morisaki Ichijiro , Kinehara Michitoki , Igarashi Seiji , Arisue Makoto
Published: August 2010

This study was conducted to identify bilirubin in deciduous teeth obtained from two patients with a history of severe liver dysfunction. Teeth were histologically analyzed and bilirubin was extracted and quantified spectrophotometrically. Histological analysis revealed a green line in the dentine running parallel to the incremental lines. A chloroform/methanol/acetic acid (30:10:0.5, v/v) extract of the teeth was evaporated and the residue dissolved in chloroform. Absorption spectra were prepared before and after the diazo reaction. The absorption maximum shifted from 450 nm before to 540 nm after the diazo reaction and was higher than that of normal deciduous teeth. These results indicate that the discolouration of teeth in patients with severe liver dysfunction is due to bilirubin deposition.
Oral wart associated with human papillomavirus type 2
Authors: Terai Masanori , Takagi Minoru , Matsukura Toshihiko , Sata Tetsutaro
Published: August 2010

More than 100 human papillomavirus (HPV) types have been identified to date. Of these, 24 types have been described as being associated with oral lesions. HPV‐2 has been frequently associated with skin lesions, but the reports of oral lesions as features of mucosal infection are limited. A biopsy specimen of an oral wart on the right palate was taken from a 48‐year‐old man and examined for the presence of HPV. The sections showed papillary growth of the epithelium with hyperkeratosis and parakeratosis, and koilocytotic changes of the cells located in the upper layers of the oral squamous cell epithelium. These histological features corresponded well to those of verruca vulgaris on the skin. Immunohistochemically, papillomavirus genus‐specific capsid antigen was detected in most of the koilocytotic cells. In addition, Southern blot hybridization analysis revealed that the lesion harbored HPV‐2 DNA. In situ hybridization with a biotinylated HPV‐2 DNA probe clearly demonstrated viral DNA in the nuclei of squamous cells, which were located in a deeper layer of the epithelium than viral antigenpositive cells.
Mixed‐type liposarcoma of the oral cavity: a case with unusual features and a long survival
Authors: Hasegawa Hiromasa , Kawakami Toshiyuki , Eda Shigeo
Published: August 2010

A case of mixed‐type liposarcoma, which showed unusual dedifferentiation in the recurrence, is reported. The rapidly growing mass in the palate of a 60‐year‐old Japanese woman first revealed a combination of myxoid liposarcoma with features resembling storiform malignant fibrous histiocytoma. The recurrent neoplasm, showing an abrupt transition between myxoid and non‐lipogenic parts, partially reverted to sclerosing well‐differentiated liposarcoma. The patient died 10.1 years after the first operation.
Expression of p16 and CDK4 in oral premalignant lesions and oral squamous cell carcinomas: a semi‐quantitative immunohistochemical study
Authors: Chen Qianming , Luo Gang , Li Bingqi , Samaranayake Lakshman P.
Published: August 2010

The protein, p16, the product of cyclin‐dependent kinase number 2 (CDKN2) gene, is one of the negative regulators of the cell cycle. CDK4, encoded by CDK4 gene, is the substrate of p16. We investigated the expression of p16 and CDK4 and their role in the progression of oral premalignant lesions (OPLs) and oral squamous cell carcinomas (OSCCs) in a Chinese cohort. A total of 74 samples were obtained from patients with hyperkeratosis (10), OPLs [30; mild (10), moderate (10) and severe (10) dysplastic lesions], OSCCs (15; 8 non‐metastatic, 7 metastatic), and normal oral tissues (10), together with local lymph nodes (9) of patients with metastatic OSCCs. A labelled streptavidin biotin (LSAB) immunohistochemistry assay was performed and a semi‐quantitative method was used to evaluate the staining intensity. The staining patterns of p16 and CDK4 were similar in all tissues and were located in both the nuclei and the cytoplasm. However, the antigen distribution characteristics and the degree of expression of both p16 and CDK4 varied at different developmental stages of the lesions. Hyperkeratotic and dysplastic lesions tended to display a progressively increasing degree of p16‐ and CDK4‐positive nuclei as compared with normal tissues. Also, positive staining cytoplasm was highly evident in OSCCs with a very low nuclear staining (P<0.05). Forty‐six of 56‐, p16‐positive cases were CDK4‐positive, while only 6 were CDK4‐positive but p16‐negative, implying a high correlation between these parameters (r=0.813, P<0.001). This study indicates that the expression of p16 and CDK4 is intimately involved in the development of OPLs and OSCCs and the likely existence of a positive feedback loop between p16 and CDK4.
Expression of cyclin D1 is correlated with poor prognosis in patients with areaca quid chewing‐related oral squamous cell carcinomas in Tiwan
Authors: Kuo Mark Yen‐Ping , Lin Chiao‐Ying , Hahn Liang‐Jiunn , Cheng Shih‐Jung , Chiang Chun‐Pin
Published: August 2010

Abnormal expression of cell cycle regulatory proteins, particularly cyclin D1, has been implicated in the pathogenesis of several types of cancer. We have examined the expression of cyclin D1 in histological sections of oral squamous cell carcinomas (SCCs) using anti‐cyclin D1 antibodies with an immunoperoxidase technique. Cyclin D1 nuclear staining was observed in 73 of 88 (83%) cases of oral SCC. In 54 of these 73 (74%) cases, positive cyclin D1 staining was also found in the normal appearing epithelium immediately adjacent to the cyclin D1‐positive SCCs. No significant correlation was found between the expression of cyclin D1 and the patients’age, sex, oral habits, cancer location and STNM status. The Kaplan‐Meier analysis showed that patients with tumors containing more than 10% cyclin D1‐positive cells had significantly shorter overall survival than those with tumors containing less than 10% cyclin D1‐positive cells or with cyclin D1‐negative tumors (P<0.05). Patients with positive lymph node status also had significantly shorter overall survival (P<0.01). These results indicate that cyclin D1 may play an important role in the genesis of oral SCC and may serve as an adjuvant marker of worse prognosis in patients with oral SCCs in Taiwan.
Recurrent aphthous stomatitis in Behçet's disease: clinical featueres and correlation with systemic disease expression and severity
Authors: Krause IIan , Rosen Yitzhak , Kaplan IIana , Milo Gai , Guedj Daniela , Molad Yair , Weinberger Abraham
Published: August 2010

Behçet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty‐five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P<0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness.
Detection of Helicobacter pylori in oral aphthous ulcers
Authors: Birek C. , Grandhi R. , McNeill K. , Singer D. , Ficarra G. , Bowden G.
Published: August 2010

A causative role for Helicobacter pylori (H. pylori) in the pathogenesis of oral mucosal ulcerations has been suggested previously. We have adopted the polymerase chain reaction (PCR) as a rapid and sensitive means to detect H. pylori in swabs of recurrent oral aphthous ulcers and in samples of other oral sites. Of the oral aphthous ulcer samples, 32 (71.8%) were found to be positive, while the saliva and plaque samples (most of them taken from the patients with aphthous ulcers) were consistently negative for H. pylori DNA, as detected by the PCR assay. Only two of the swab samples from the tongue (collected at the time of concurrent, H. pylori‐positive oral aphthous ulcers) were found to be positive. The data suggest that H. pylori may be associated frequently with recurrent oral aphthous ulcers, and are consistent with previous studies indicating that saliva and plaque are not likely sources of contamination with this microorganism. There was no apparent correlation with HIV status (infection with human immunodeficiency virus). The possible pathogenic significance of Helicobacter pylori in oral ulcerations is discussed.
Infrequent p53 mutations in patients with areca quid chewing‐associated oral squamous cell carcinomas in Taiwan
Authors: Kuo Mark Yen‐Ping , Huang Jehn‐Shyun , Hsu Hey‐Chi , Chiang Chun‐Pin , Kok Sang‐Heng , Kuo Ying‐Shiung , Hong Chi‐Yuan
Published: August 2010

Mutations in the conserved regions (exons 5‐9) of the p53 gene were investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using polymerase chain reaction‐single strand conformation polymorphism and DNA sequencing analyses. P53 mutations were detected in 2 of 37 (5.4%) oral SCC cases. One tumor sample (case 23) showed a mis‐sense point mutation at codon 177, changing CCC to CTC, which resulted in a substitution of proline to leucine in the p53 protein. The other tumor (case 33) had a point mutation at codon 266, changing GGA to AGA and causing a substitution of glycine to arginine in the p53 protein. These two patients with p53 mutations did not have an areca quid chewing habit. These results suggest that mutations in the p53 gene may not play a role in the pathogenesis of human oral SCCs in Taiwan. Recently, we have shown that positive p53 staining was observed in 47 of 81 (58%) cases of oral SCC. The discrepancies between positive p53 protein staining and the low prevalence of p53 mutation in oral SCCs indicate that other mechanism(s) are involved in p53 overexpression.
Expression of p53 oncoprotein increases intratumoral microvessel formation in human salivary gland carcinomas
Authors: Doi Rieko , Kuratate Itaru , Okamoto Eiji , Ryoke Kazuo , Ito Hisao
Published: August 2010

P53 protein and vascular endothelial growth factor (VEGF) expression, and mean intratumoral microvessel density (IMVD) were studied by immunohistochemistry in 31 salivary gland carcinoma, consisting of 11 adenoid cystic carcinomas (AdCCs), 10 mucoepidermoid carcinomas (MECs), 7 acinic cell carcinomas (AcCCs), and 3 squamous cell carcinomas (SCCs). Cases with p53 protein in more than 20% of tumor cells were detected in one AdCC, four MECs, one AcCC, and two SCCs. Both frequency of p53 and VEGF expression, and mean IMVD, were higher in the MECs and SCCs than in the AdCCs and AcCCs. Similarly, both VEGF expression and mean IMVD were significantly higher (P 0.05) in the eight p53‐positive tumors than in the 23 negative tumors. Six cases with survival periods less than 5 years showed significantly higher frequency of p53 and VEGF expression and of mean IMVD than those with longer survival periods. These results indicate that p53 expression might partly correlate with VEGF expression and mean IMVD, and be a factor in the survival of patients with salivary gland carcinomas.
Initiation of ectopic epithelial calcification in a calcifying odontogenic cyst
Authors: Satomura K. , Nakanishi H. , Fujisawa K. , Hayashi E. , Nagayama M.
Published: August 2010

Ultrastructural observation was performed on a calcifying odontogenic cyst (COC) associated with an odontoma and arising in the right mandibular region of an 8‐year‐old Japanese boy. Four types of cells were identified in the epithelial layer of the COC. The basal cells were low columnar in shape and contained some intracellular organelles. They were attached to the neighboring cells with a few desmosomes and resembled inner enamel epithelium of the normal enamel organ. The stellate reticulum‐like cells, polygonal in shape, possessed desmosomes and many cytoplasmic projections. Some intracellular organelles and a few bundles of tonofilaments were observed in the cyutoplasm. The light oval cells that were pale staining with toluidine blue contained dilated membranous organelles and many relatively evenly distributed tonofilaments. These cells were usually scattered in the vicinity of the focal accumulations of ghost cells, and the cell membrane was discontinuous in parts. The ghost cells contained many bundles of tonofilaments that were 60–240 nm in diameter and arranged in various directions. No intact intracellular organelles were noted in the cytoplasm. They were attached to the neighboring ghost cells with some desmosomes and their cell membrane was discontinuous in parts. A variety of vesicles, 90‐450 nm in diameter, were scattered among the tonofilament bundles. Some of these contained needle‐like crystals that were considered to be initial calcification sites in ghost cells. These vesicles presented morphological similarities to matrix vesicles, and it is therefore suggested that matrix vesicle‐like structures are deeply involved with initiation of calcification of ghost cells in COC.
Expression of laminin‐5 in ameloblastomas and human fetal teeth
Authors: Salo Tuula , Kainulainen Tiina , Parikka Mataleena , Heikinheimo Kristiina
Published: August 2010

Extracellular matrix proteins have been shown to play important roles in the cell migration and differentiation in both normal and pathological conditions. In the present study, we used immunohistochemistry and in situ hybridization to determine the distribution of laminin‐5 in ameloblastomas and developing human teeth. In ameloblastomas, the immunoreaction for the laminin‐5 γ2 chain was confined to the tumor cells of the peripheral area. The staining reaction was variable, being mostly weak and fragmented in the basement membrane structures surrounding the neoplastic islands. Some peripheral epithelial cells and some invading small ameloblastoma cell islands showed intense intracellular staining for the γ2 chain. Tumor cells in the proliferating areas of ameloblastomas expressed γ2 chain mRNA. The laminin‐5 γ2 chain was located beneath the dental lamina and in the outer, but not in the inner, enamel epithelium of the developing teeth. During the early hard tissue apposition stage, intense staining for the γ2 chain was confined to ameloblasts, which also gave a strong signal for γ2 chain mRNA. These results suggest that laminin‐5 may contribute to the infiltrative and progressive growing potential of ameloblastomas. During human tooth development, however, laminin‐5 may participate in the terminal differentiation of ameloblasts and in enamel matrix formation.
Immunohistochemical analysis of bcl‐2 family proteins in benign and malignant ameloblastomas
Authors: Kumamoto Hiroyuki , Ooya KiyoshiOoya
Published: August 2010

To study the possible roles of bel‐2 family proteins in oncogenesis and cytodifferentiation of odontogenic epithelium, the expression of bel‐2, bel‐x and bax proteins was examined immunohistochemically in tooth germs and various types of ameloblastoma. In ameloblastomas, bel‐2 and bel‐x proteins were expressed intensely in peripheral columnar cells and weakly in central polyhedral cells, while bax protein reactivity was low. In variants of ameloblastoma, no expression of these proteins was found in the keratinizing areas or granular cell clusters. Basal cell ameloblastomas showed intense reactivity for bel‐2 and bel‐x proteins, but slight or no reactivity for bax protein. These results indicate that in amel‐oblastomas the bel‐2 family proteins might function primarily as anti‐apoptotic factors, reflecting proliferative activity. Malignant ameloblastomas showed decreased reactivity for bcl‐2 protein and increased levels of bax protein as compared with benign ones.
Simple bone cyst of the mandibular condyle with severe osteoarthritis: report of a case
Authors: Ogasawara Toshiyuki , Kitagawa Yoshimasa , Ogawa Toru , Yamada Tetsushi , Yamamoto Sachiko , Hayashi Kaihei
Published: August 2010

A rare case of simple bone cyst in the mandibular condyle of a 33‐year‐old woman is reported. The condition was difficult to diagnose because the cyst was accompanied by severe osteoarthritis. T1‐weighted magnetic resonance (MR) images revealed a cystic lesion with intermediate signal intensity within the condylar head and an irregular margin with intermediate signal intensity on the superior surface of the condyle. The patient was treated by high condylectomy, discectomy and reconstruction by sagittal split ramus osteotomy. Histopathological examination showed a simple bone cyst in the condylar head and erosion of the anterior articular surface due to degenerative changes.
Immunohistochemical evaluation of Fhit protein expression in oral squamous cell carcinomas
Authors: van Heerden W. F. P. , Swart T. J. P. , van Heerden M. B. , van Rensburg E. J. , Engelbrecht S. , Dreyer L. , Huebner K.
Published: August 2010

van Heerden WFP, Swart TJP, van Heerden MB, van Rensburg EJ, Engelbrecht S, Dreyer L, Huebner K: Immunohistochemical evaluation of Fhit protein expression in oral squamous cell carcinomas. J Oral Pathol Med 1999; 28: 433–7. © Munksgaard, 1999.

The expression of Fhit (fragile histidine triad) protein in oral squamous cell carcinoma (OSCC) and adjacent oral epithelium was evaluated by immunohisto‐chemistry on formalin‐fixed paraffin‐embedded blocks of 32 cases of OSCC. Rabbit polyclonal anti‐GST‐Fhit antiserum at 1:600 was used, after antigen enhancement in a microwave pressure cooker, in a saturated lead thiocyanate solution. This antiserum has been shown specifically to detect human Fhit by immunohistochemistry at dilutions up to 1:10,000. The Fhit protein expression was evaluated using both the intensity and extent of staining. Normal stratified squamous epithelium showed strong positivity, especially in the stratum spinosum and areas of keratinisation. Basal and parabasal cells were negative or expressed low levels of Fhit relative to the squamous epithelium. Mild and moderate epithelial dysplasia showed Fhit expression in the superficial layers, while Fhit expression was absent from severely dysplastic lesions. A reduction or loss of Fhit expression was found in 21 (66%) of the OSCC. The alterations in Fhit protein expression in OSCC, and not in normal tissues, are consistent with the proposal that Fhit inactivation plays a role in oral carcinogenesis.
Primary chronic osteomyelitis associated with synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO syndrome)
Authors: Eyrich G. K. H. , Harder C. , Sailer H. F. , Langenegger T. , Bruder E. , Michel B. A.
Published: August 2010

Eyrich GKH, Harder C, Sailer HF, Langenegger T, Bruder E, Michel BA: Primary chronic osteomyelitis associated with synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO syndrome). J Oral Pathol Med 1999; 28: 456–64. © Munksgaard, 1999.

Diffuse sclerosing osteomyelitis may indicate the mandibular localisation of the SAPHO syndrome. Twelve patients with diffuse sclerosis of the mandible were examined for symptoms of the SAPHO syndrome. Nine patients were found to have primary chronic osteomyelitis and eight of these represented a SAPHO syndrome. Results in this series support the hypothesis of an association between primary chronic osteomyelitis and the SAPHO syndrome.
Collagenous fibroma (desmoplastic fibroblastoma) presenting as a parotid mass
Authors: Ide Fumio , Shimoyama Tetsuo , Horie Norio , Tanaka Hiroshi
Published: August 2010

Ide F, Shimoyama T, Horie N, Tanaka H: Collagenous fibroma (desmoplastic fibroblastoma) presenting as a parotid mass. J Oral Pathol Med 1999; 28: 465–8. © Munksgaard, 1999.

We describe the case of a 50‐year‐old man who was found to have a painless, slow‐growing parotid mass of 10 months duration. At surgery, a well‐delimited, lobulated 4 times 5 cm tumor was located on the deep lobe of the left parotid gland, adhering to the parotid sheath and masseteric fascia. Follow‐up 6 years later has shown no evidence of recurrence. Cardinal morphologic features included multiple nodules of sparsely distributed stellate‐or spindle‐shaped fibroblasts within a collagenous or myxocollagenous stroma. Fascial involvement and entrapment of salivary gland were focally identified at the edges. Tumor cells were diffusely positive for vimentin with faint focal staining for α‐smooth muscle actin. These findings satisfied the diagnostic criteria for collagenous fibroma (desmoplastic fibroblastoma). Ours represents the first report of this tumor type mimicking a parotid tumor.
Loss of differentiation of 4NQO‐induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF‐pi and an altered receptor profile
Authors: Davies Maria , Paterson Ian C. , Stone Andrea , Huntley Susan , Patel Vyomesh , Curtis Rory , Matthews John B. , Pring Miranda , Eveson John W. , Prime Stephen S.
Published: August 2010

This study examined the metastatic capacity of clonal populations of 4NQO‐induced rat malignant oral keratinocytes following orthotopic transplantation to athymic mice. Polygonal and spindle cells formed well‐differentiated squamous cell carcinomas (keratin positive and vimentin negative) and undifferentiated spindle cell tumours (keratin negative and vimentin positive), respectively, in almost 100% of animals at the site of inoculation (floor of mouth). Transplantation of 5 × 106 cells of either cell type at high cell density resulted in approximately 50% of animals forming pulmonary metastases. By contrast, inoculation of 2 × 106 differentiated polygonal cells resulted in the formation of significantly fewer pulmonary metastases than the undifferentiated spindle cells. A single well‐differentiated clone of polygonal cells and 3 of 4 of the undifferentiated spindle cell lines produced comparable levels of TGF‐β1. One undifferentiated spindle cell line expressed significantly more TGF‐β1 and, following transplantation orthotopically, fewer animals formed pulmonary metastases despite the formation of primary tumours in almost all grafted animals, suggesting that TGF‐β1 can act as a tumour suppressor in this cell type. All cell lines produced comparable amounts of TGF‐β2. The clones of polygonal cells were markedly inhibited and the spindle cells were only partially inhibited by exogenous TGF‐β1. Both cell types expressed high‐affinity TGF‐β cell surface receptors; the ratio of type I to type II TGF‐β receptors was 1.0: < 3.0 in the spindle cells and 1.0:17.9 in the polygonal clone. The results suggest that differentiated rat malignant oral keratinocytes are less aggressive and have a decreased potential to metastasise than their undifferentiated spindle cell counterparts. This may be attributable, in part, to a change in TGF‐β receptor profile leading to the partial loss of response to exogenous TGF‐β1.
Calcifications of the disc of the temporomandibular joint
Authors: Jibiki Masato , Shimoda Shinji , Nakagawa Yoichi , Kawasaki Kenzo , Asada Koichi , Ishibashi Katsunori
Published: August 2010

Calcified lesions of the temporomandibular joint discs obtained from 135 human cadavers were studied. Calcifications were observed in 92 of 250 discs by soft x‐ray radiography. Studies by light and electron microscopy and x‐ray diffraction revealed that there were two different types of calcification in the discs: apatite crystal deposition with or without ossification, and calcium pyrophosphate dehydrate (CPPD) crystal deposition. Calcifications were recognized more frequently posteriorly than anteriorly, and were related to disc perforation. The results of this investigation suggest that disc degeneration, which may occur as a result of aging or mechanical stress, causes calcifications.
The molecular markers for prognostic evaluation of areca‐associated buccal squamous cell carcinoma
Authors: Liu Chung‐Ji , Chang Kuo‐Wei , Chao Shou‐Yee , Kwan Po‐Cheung , Chang Shun‐Min , Yen Rui‐Yin , Wang Chun‐Yu , Wong Yong‐Kie
Published: August 2010

Background:  Buccal squamous cell carcinoma (BSCC) is the most frequently occurring oral cancer in Asians due to the popularity of areca use in this area. The aim of the present study was to evaluate the survival of areca‐associated BSCC associated with multiple molecular markers.

Methods:  Using immunohistochemistry, we evaluated the survival of a cohort of 55 patients with BSCC being followed long term, as correlated to the expression of variable markers.

Results:  We found that p53, p21, Rb, cyclin D1 (CCD1), MDM2, and γ‐catenin were positive in 81, 60, 70, 31, 88, and 44% of patients, respectively. Subjects with −ve immunoreactivity for CCD1, and +ve immunoreactivity for MDM2 and γ‐catenin had significantly better survival than subjects with the opposite immunoreactive pattern. Kaplan–Meier survival curves confirmed this association.

Conclusion:  The data indicate that expression of CCD1, MDM2, and γ‐catenin might serve as potential prognostic markers for BSCC in areca‐using patients.
Relationship between major and minor salivary gland mucoepidermoid carcinoma malignancy grading and presence of stromal myofibroblasts: immunohistochemical study
Authors: Sobral Ana Paula Veras , Loducca Silvia Vanessa L. , Nunes Fábio Daumas , De Araújo Ney Soares , Kowalski Luiz Paulo , De Araújo Vera Cavalcanti
Published: August 2010

Objective:  Mucoepidermoid carcinoma (MEC) is the most common malignant salivary tumour, classified as low, intermediate and high grade. Myofibroblasts are the main stromal component and are included as prognostic factor in some tumours. The aim of this study was to evaluate the myofibroblasts in the stroma of MEC with possible relationship to malignancy grading.

Methods:  Twenty‐five cases of MEC (six low grade, 11 intermediate grade, four high grade and four metastasis) were stained for vimentin, desmin and smooth muscle actin (SMA) for the identification of myofibroblasts. Transforming growth factors (TGFβ1 and TGFβRII) were also assessed in our study.

Results:  Myofibroblasts were present in all cases, in amounts varying according to histological grading. TGFβ1 was positive in squamous cells of intermediate grade tumours, and in the stroma of only four cases. TGFβRII was positive in most squamous and intermediate cells, regardless of malignancy grading.

Conclusions:  Our study showed that the analysis of neoplastic stroma must be added to the studies of neoplastic cells to draw a better picture leading to tumour diagnosis and prognosis.
Treatment of gingival lichen with free palatal grafts
Authors: Axéll Tony , Henriksen Birgitte Moesgaard
Published: August 2010

Background:  Recalcitrant gingival erythematous lichen planus/lichenoid lesions comprise a considerable therapeutic problem. The objective of this study was to evaluate the therapeutic effect of grafting keratinized oral palatal mucosa to the sites of gingival lichen.

Methods:  In 12 patients 20 grafts were transplanted to buccal gingival lesions. Mean age of the patients was 59.8 ± 7.1 years (range 46–71 years). The mean observation time was 32 ± 32.7 months (range 5–97 months).

Results:  On a 4‐point clinical grade scale (0–3), 12 (60%) transplants showed complete healing grade 3, six (30%) grade 2 and two (10%) grade 1.

Conclusions:  Using oral mucosal grafts from the palatal mucosa for the treatment of recalcitrant erythematous gingival lichen planus/lichenoid lesions seems to be a promising treatment modality.
Detection of antibodies against p63 and p73 isoforms in sera from patients diagnosed with oral lichen planus
Authors: Ebrahimi Majid , Wahlin Ylva‐Britt , Coates Philip J. , Wiik Allan , Roos Göran , Nylander Karin
Published: August 2010

Background:  Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa. Despite numerous publications and intense research, the etiology of OLP is still unknown, however, autoimmunity as a possible causative factor has been discussed.

Methods:  In the present study sera from 20 patients clinically and histologically diagnosed with OLP were analyzed for antibodies directed toward p53, p63, and p73 using Western blot.

Results:  Sera from two patients reacted with all six p63 isoforms, and one also with p73. The strongest reaction was noted against the TAp63β protein, which is the most potent transactivator of all p63 proteins and is implicated in the differentiation of stratified epithelia.

Conclusions:  This is the first demonstration of antibodies directed against all p63 and some p73 isoforms in sera from patients diagnosed with OLP.
Oral and pharyngeal cancer mortality rates in Mexico, 1979–2003
Authors: Anaya‐Saavedra Gabriela , Ramírez‐Amador Velia , Irigoyen‐Camacho María Esther , Zimbrón‐Romero Araceli , Zepeda‐Zepeda Marco Antonio
Published: August 2010

Background:  In Mexico, information on oral and pharyngeal cancer (OPC) is scarce. The purpose of this study was to explore the trends in OPC mortality rates in Mexico from 1979 through 2003 and to describe the distribution of OPC deaths for selected socio‐demographic variables for the period of 2001–2003.

Material and methods:  Annual crude and age‐adjusted mortality rates were obtained by gender and site of lesion, using the 2003 WHO World standard million population. The Poisson regression model was used to detect a trend in the mortality rates, testing the hypothesis β1 = 0. Also, the annual percentage change (APC) was computed over the age‐adjusted rates.

Results:  The total number of OPC deaths during the period 1979–2003 was 15 576. The age‐adjusted mortality rate was 1.13/100 000 in 1979 and 1.08/100 000 in 2003. Oral cancer was more frequently found than salivary gland and pharyngeal cancer (41.5% vs. 13.4% and 17.1%). The tongue (19%) was the most frequent oral affected site. The Poisson regression analysis indicated a stationary trend in cancer mortality rate; also, the APC regression model showed no increase or decrease in OPC from 1979 to 2003.

Conclusions:  Oral and pharyngeal cancer mortality rates in Mexico were low compared to most countries, and remained stable in the past two decades.
Expression of hypoxia‐inducible factor‐1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan
Authors: Lin Pin‐Yi , Yu Chuan‐Hang , Wang Jeng‐Tzung , Chen Huang‐Hsu , Cheng Shih‐Jung , Kuo Mark Yen‐Ping , Chiang Chun‐Pin
Published: August 2010

Background:  Overexpression of hypoxia‐inducible factor‐1α (HIF‐1α) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers.

Methods:  This study examined the expression of HIF‐1α in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry.

Results:  We found that the mean nuclear HIF‐1α labeling indices (LIs) increased significantly from NOM (9 ± 6%) through mild OED (25 ± 18%), moderate OED (41 ± 27%), and severe OED (42 ± 22%) to OSCC samples (55 ± 23%, P < 0.001). A significant correlation was found between the higher mean nuclear HIF‐1α LI and OSCCs with larger tumor size (P < 0.001), regional lymph node metastasis (P < 0.001), or more advanced clinical stages (P < 0.001). Only larger tumor size (P = 0.002) and nuclear HIF‐1α LI ≥ 60% (P = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan–Meier curve showed that OSCC patients with a nuclear HIF‐1α LI ≥ 60% had a significantly poorer cumulative survival than those with a nuclear HIF‐1α LI < 60% (log‐rank test, P = 0.022).

Conclusions:  We conclude that the expression of HIF‐1α is an early event in oral carcinogenesis. The nuclear HIF‐1α LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.
One‐year follow‐up of the effect of fixed orthodontic treatment on colonization by oral candida
Authors: Gündüz Arslan Seher , Akpolat Nezahat , Kama Jalan Devecioğlu , Özer Törün , Hamamcı Orhan
Published: August 2010

The aim of this study was to assess quantitative and qualitative alterations in the carrier rate of Candida spp. in south‐eastern Turkey among adolescents, and to investigate the effect of fixed orthodontic appliances on the Candida count in a 1‐year follow‐up study. In the first phase of the study, the oral Candida carriage rate of 72 patients was evaluated. Samples were collected from the dorsal surface of the tongue, the mid‐palate and saliva. In the second phase of the study, 42 patients who were determined to be carriers of oral Candida were treated with fixed orthodontic appliances, and from these patients a second set of samples were collected from the saliva and the orthodontic brace surfaces of eight teeth adjacent to the enamel surfaces. The saliva samples were collected before and during orthodontic treatment at 1st, 6th and 12th month, and samples from the braces were collected during the 1st, 6th and 12th month of treatment. Forty‐two of the 72 patients (58.5%) were oral Candida carriers. The distribution of Candida spp. in these patients was as follows: (i) Candida albicans was identified in 31 patients (73.8%), (ii) C. tropicalis, C. krusei and C. kefyr were found in three patients each (7.14%) and (iii) C. parapsilosis occurred in two patients (4.76%). During orthodontic treatment, the micro‐organism count increased both in the saliva and on tooth surfaces. The results indicate that the prevalence of oral Candida spp. is high in young adults in south‐eastern Turkey and that the Candida counts increase when braces are involved.
AgNOR cut‐point to distinguish mild and moderate epithelial dysplasia
Authors: Chattopadhyay Amit , Ray Jay G.
Published: August 2010

Background:  Distinguishing mild and moderate epithelial dysplasia is difficult and controversial. We demonstrated earlier that silver‐stainable nucleolar organizer region (AgNOR) is a simple, inexpensive and quantifiable method which can standardize this distinction reliably.

Objective:  To establish a cut‐point mean AgNOR count for epithelial dysplasia validated by bootstrapping.

Methods:  One hundred oral leukoplakia biopsies at Dr R. Ahmed Dental College, Kolkata, India, examined for epithelial dysplasia using standard method (gold standard) were assessed for their mean AgNOR counts. A cut‐point was selected employing receiver operating characteristic (ROC) curve. This estimate was stabilized by 10 000 resamples (with replacement) using parametric and non‐parametric bootstrap, a Monte Carlo statistical method, corrected for bias to estimate standard errors (SE) of cut‐point.

Results:  Area under the curve (AUC) was 74%; non‐parametric method suggested mean AgNOR cut‐point = 2.42 AgNORs/nucleus; parametric method suggested cut‐point = 2.57. The cut‐point 95% confidence intervals (CIs) (bias corrected and accelerated) from parametric method (2.31; 2.66) was lower than non‐parametric (2.43; 2.82).

Conclusion:  Applying a conservative paradigm, taking the lowest of all bootstrap 95% CIs, we suggest that mean AgNOR count of 2.3 be used as a cut‐point for distinguishing between mild and moderate dysplasia. This strategy will provide an inexpensive, meaningful, definitive, reproducible and consistent diagnostic test for epithelial dysplasia.
Orofacial granulomatosis: review on aetiology and pathogenesis
Authors: Tilakaratne W. M. , Freysdottir J. , Fortune F.
Published: August 2010

Orofacial granulomatosis (OFG) is considered as an uncommon disease and nomenclature of the disease was subjected to debate for a long time. Although various aetiological agents such as food substances, food additives, dental materials and various microbiological agents have been implicated in the disease process its precise pathogenesis is yet to be elucidated. Delayed type of hypersensitivity reaction appears to play a significant role, although the exact antigen inducing the immunological reaction varies in individual patients. However, evidence for the role of genetic predisposition to the disease is sparse. The underlying immunological mechanism appears to show some similarities between OFG and Crohn’s disease, emphasizing the need for more comparative studies of the two entities. Therefore, we propose the term idiopathic OFG as a better term for those cases restricted to oral region without any identifiable known granulomatous disease and the diagnosis should not be changed until the patient develops systemic manifestations of a specific granulomatous condition. This review attempts to discuss the role of different aetiological agents and certain aspects of pathogenesis of OFG.
RNA from brush oral cytology to measure squamous cell carcinoma gene expression
Authors: Schwartz Joel L. , Panda Suchismita , Beam Craig , Bach Laura E. , Adami Guy R.
Published: August 2010

Background:  RNA expression analysis of oral keratinocytes can be used to detect early stages of disease such as oral cancer or to monitor on‐going treatment responses of the same or other oral diseases. A limitation is the inability to obtain high quality RNA from oral tissue without using biopsies. While oral cytology cell samples can be obtained from patients in a minimally invasive manner they have not been validated for quantitative analysis of RNA expression.

Methods:  As a starting point in the analysis of tumor markers in oral squamous cell carcinoma (OSCC), we examined RNA in brush cytology samples from hamsters treated with dibenzo[a,l]pyrene to induce oral carcinoma. Three separate samples from each animal were assessed for expression of candidate marker genes and control genes measured with real‐time RT‐PCR.

Results:  Brush oral cytology samples from normal mucosa were shown to consist almost exclusively of epithelial cells. Remarkably, ß‐2 microglobulin and cytochrome p450, 1B1 (CYP1B1) RNA showed potential utility as markers of OSCC in samples obtained in this rapid and non‐surgical manner.

Conclusion:  Brush oral cytology may prove useful as a source of RNA for gene expression analysis during the progression of diseases of the oral epithelium such as OSCC.
Expression of melanoma‐associated antigens in oral squamous cell carcinoma
Authors: Ries Jutta , Vairaktaris Eleftherios , Mollaoglu Nur , Wiltfang Joerg , Neukam Friedrich W. , Nkenke Emeka
Published: August 2010

Background:  Melanoma‐associated antigens‐A (MAGE‐A) are expressed in a variety of tumors but not in normal tissues. Thus, their detection is highly specific to cancer cells, which makes them potential targets for the diagnosis, prognosis and also immunotherapy of neoplastic diseases.

Methods:  To determine the expression pattern and potential role of MAGE‐A antigens in oral squamous cell carcinoma (OSCC), expression patterns of MAGE‐A1–A6 and A12 were analyzed in 55 OSCC and 20 healthy oral mucosa using high‐sensitive reverse transcription‐nested polymerase chain reaction (RT‐nPCR).

Results:  The 85.45% of tumor specimens expressed at least one of these genes. A significant correlation between the expression of MAGE‐A1–A6 and A12 and malignancy was ascertained (P = 0.0001). On the contrary, none of the normal mucosal specimens expressed one of the MAGE‐A subtypes. Antigen expression did not correlate with clinicopathological parameters, such as TNM classification, grading and clinical stage of OSCC.

Conclusions:  Multiple simultaneous detection of MAGE‐A1–A6 and A12 expression has been found to be more specific and sensitive than the detection of single MAGE‐A antigen for the diagnostic and prognostic evaluation of OSCC. In addition, monitoring the expression of several MAGE‐A subtypes may determine suitable immunotherapeutic targets. Subsequently, coexpressed genes may be warranted for developing polyvalent vaccines.
Patients with oral cancer developing from pre‐existing oral leukoplakia: do they do better than those with de novo oral cancer?
Authors: Weijers Manon , Ten Hove Ivo , Allard Remy H. B. , Bezemer Dick P.D. , Van Der Waal Isaäc
Published: August 2010

Background:  It has been suggested that patients with squamous cell carcinomas derived from oral leukoplakia have a better prognosis than patients with carcinomas that are not associated with oral leukoplakia.

Aim:  To study the mortality rate of 19 patients with a squamous cell carcinoma derived from pre‐existing oral leukoplakia.

Method:  The mortality rate of 19 patients with a proven oral squamous cell carcinoma derived from a pre‐existing oral leukoplakia was compared with that of a similar size group of patients with oral carcinoma without a pre‐existing oral leukoplakia, being matched for gender, age, smoking habits, use of alcohol, oral subsite and histopathologic grade. Treatment in all patients was primarily by surgical excision. The mortality rates up to 5 years have been computed according to the Kaplan–Meier method.

Result:  No significant difference of the mortality rates up to 5 years of follow‐up was observed between the two groups of patients.

Conclusion:  Patients with oral cancer developing from pre‐existing oral leukoplakia do not do better than those with de novo oral cancer.
Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan
Authors: Yen Ching‐Yu , Liu Shyun‐Yeu , Chen Chung‐Ho , Tseng Hung‐Fu , Chuang Li‐Yeh , Yang Cheng‐Hong , Lin Ying‐Chu , Wen Cheng‐Hao , Chiang Wei‐Fan , Ho Chang‐Hsuan , Chen Hsiang‐Chi , Wang Shaio‐Ting , Lin Cheng‐Wen , Chang Hsueh‐Wei
Published: August 2010

Background:  Many single nucleotide polymorphisms (SNPs) have been found to be associated with oral cancer but the biological interactions through SNPs are seldom addressed. In this study, we focused on the joint effect for SNP combinations of four DNA repair genes, X‐ray repair cross‐complementing groups (XRCCs) 1–4, involved in major cancer‐related pathways.

Methods:  Single nucleotide polymorphism genotyping was determined using by polymerase chain reaction‐restriction fragment length polymorphism in this study (case = 103, control = 98). Different numbers of combinational SNPs with genotypes called the pseudo‐haplotypes from these chromosome‐wide genes were used to evaluate their joint effect on oral cancer risk.

Results:  Except for XRCC2 rs2040639‐AG, none of these SNPs was found to individually contribute to oral cancer risk. However, for two combined SNPs, the proportion of subjects with oral cancer was significantly higher in the pseudo‐haplotype with AG‐CC genotypes in rs2040639‐rs861539 (XRCC2–XRCC3) compared with those with non‐AG‐CC genotypes. Similarly, the pseudo‐haplotype of rs2040639–rs861539–rs2075685 (XRCC2–XRCC3–XRCC4) and rs2040639–rs861539–rs2075685–rs1799782 (XRCCs 1–4) with specific genotype pattern (AG‐CC‐TG and CT‐AG‐CC‐TG) among three and four combinational SNPs were significantly associated with oral cancer. After controlling for age, gender, smoking, drinking, and betel nut chewing, the estimated odds ratio of oral cancer were 2.45, 5.03, and 10.10 for two, three and four specific SNP combinations, respectively, comparing these specific pseudo‐haplotypes to their corresponding non‐pseudo‐haplotypes.

Conclusion:  We have identified the potential combined XRCCs 1–4 SNPs with genotypes that were associated with oral cancer risk and may have an impact on identification of a high‐risk population.
An altered keratinocyte phenotype in oral submucous fibrosis: correlation of keratin K17 expression with disease severity
Authors: Lalli Anand , Tilakaratne Wanninayake M. , Ariyawardana Anura , Fitchett Caroline , Leigh Irene M. , Hagi‐Pavli Eleni , Cruchley Alan T. , Parkinson E. Kenneth , Teh Muy‐Teck , Fortune Farida , Waseem Ahmad
Published: August 2010

Oral submucous fibrosis (OSF) is characterized by abnormal collagen metabolism in the submucosal connective tissue. Its influence on the overlying epithelium is not known but about 14% of OSF cases undergo malignant transformation to squamous cell carcinoma indicating association with abnormality of the epithelium. Here, we have defined the keratin expression profile, by immunohistochemistry and quantitative image analysis, using a panel of 22 anti‐keratin monoclonal antibodies on 28 OSF samples. We observed an increase of K1 and K10 in the suprabasal layers, induction of K6 in the basal layer and complete loss of K19 in the epithelium. Furthermore, there was increased K17 expression in the suprabasal layers, which correlated with disease severity. In a subset of the most severe OSF cases (14%), K17 expression was completely lost in the basal layer which might define them to be at most risk to undergo malignant transformation. There was no detectable expression of K8, K18, K7 and K9 and the expression of K4, K13, K14, K15 and K16 did not change in OSF. We propose that the altered keratin profiles could be useful as histological diagnostic markers and provide important insights into the pathogenesis of the disease and its predisposition to malignancy.