Prevalence of human papillomavirus in oral cancer in Asia: A systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) across Asian countries, focusing on South and Southeast Asia. METHODS: A systematic search of four databases-MEDLINE/PubMed, EMBASE, Scopus, and ProQuest-was conducted to identify observational studies published between January 2013 and December 2023. The pooled prevalence of HPV was estimated using random-effects models, and subgroup analysis was performed to investigate the source of heterogeneity. RESULTS: A total of 77 studies were included, comprising 7289 OSCC cases from 11 countries. The pooled HPV prevalence in OSCC was 23.1% (95% CI 17.9-28.7, I2 = 96.7%). South Asia had the highest prevalence (27.1%), followed by East Asia (19.4%), and Southeast Asia (16.7%). Two subtypes were commonly reported: HPV-16 (9.1%) and HPV-18 (5.1%). Anatomical subsites, buccal mucosa (34.0%), and floor of the mouth (33.2%) had similar ranges of HPV prevalence. All studies exhibited a high degree of heterogeneity, with the OSCC location and risk of bias identified as potential sources of heterogeneity. CONCLUSIONS: Due to the high HPV prevalence in OSCC in Asia, HPV detection in routine pathology practice is recommended. Future studies should be conducted in multicentre settings using similar HPV detection methods and reporting detailed demographic and clinical information on oral sub-sites.

Central odontogenic fibroma: retrospective study of six cases with variable histopathologic features using 2022 WHO classification.

BACKGROUND: Central odontogenic fibroma (COF) is a rare benign odontogenic tumor with a wide range of histopathologic features. We evaluated COF diagnosed in our institute with 16 years' experience using 2022 WHO classification. METHODS: Our archives were reviewed and cases diagnosed as COF were selected. Clinical, radiographic and microscopic features were tabulated and analyzed. RESULTS: Of 13,736 specimens, six cases (0.04%) of COF were discovered. Patients ranged in age from 14 to 44 years. There were two males and four females. Maxilla and mandible were affected equally. Five cases showed radiolucent appearance (4 unilocular, 1 multilocular) and one case showed a mixed radiolucent-radiopaque pattern. Histopathologically, three cases were conventional type (2 epithelium-rich, 1 epithelium-poor). Two cases were the hybrid COF with central giant cell granuloma (CGCG) and one of which was also associated with secondary aneurysmal bone cyst (ABC). The last case with a mixed radiolucent-radiopaque pattern was the ossifying subtype. CONCLUSION: Our results demonstrated that COF is a rare odontogenic tumor and exhibits diverse radiographic and microscopic appearances. The triphasic tumor consisting of the COF, CGCG and ABC, is reported here for the first time, while the ossifying subtype is considered the tenth case reported in the English-language literature. Oral and maxillofacial pathologists and other healthcare personnel must be aware of this rare odontogenic tumor and its variants to achieve the definite diagnosis. CLINICAL TRIAL NUMBER: Not applicable.

Immunohistochemical expression of SPARC in odontogenic keratocysts: a comparative study with other odontogenic cysts.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been shown to modulate aggressive behavior in several benign and malignant tumors. Little is known about SPARC expression in odontogenic keratocyst (OKC), an odontogenic cyst with an aggressive nature. To the best of our knowledge, only one study has been investigated the expression of this protein in OKCs. This study aimed to characterize SPARC expression in OKCs. Additionally, to determine whether SPARC is associated with aggressive behavior in OKCs, SPARC expression in OKCs was compared with radicular cysts (RCs), dentigerous cysts (DCs) and calcifying odontogenic cysts (COCs). These odontogenic cysts showed no or less aggressive behavior. METHODS: SPARC expression was evaluated in 38 OKCs, 39 RCs, 35 DCs and 14 COCs using immunohistochemistry. The percentages of positive cells and the intensities of immunostaining in the epithelial lining and the cystic wall were evaluated and scored. RESULTS: Generally, OKCs showed similar staining patterns to RCs, DCs and COCs. In the epithelial lining, SPARC was not detected, except for ghost cells in all COCs. In the cystic wall, the majority of positive cells were fibroblasts. Compared between 4 groups of odontogenic cysts, SPARC expression in OKCs was significantly higher than those of RCs (P < 0.001), DCs (P < 0.001) and COCs (P = 0.001). CONCLUSIONS: A significant increase of SPARC expression in OKCs compared with RCs, DCs and COCs suggests that SPARC may play a role in the aggressive behavior of OKCs.

Hepatic expression of HGF/C-met and native liver survival in biliary atresia.

BACKGROUND: The prognosis of biliary atresia (BA) remains difficult to predict. This study evaluated the roles of hepatocyte growth factor (HGF) and its receptor (C-met) towards clinical outcome and native liver survival. METHODS: Hepatic HGF and C-met expression were determined using immunohistochemistry from liver biopsies of 41 BA patients during Kasai operation, and 17 non-cholestatic patients. The HGF and C-met expression was visually scored as per its intensity and percentage of stained area. BA patients were classified as high- and low-HGF and C-met receptor status. Native liver survival was compared between the two groups at 3-year follow-up. Data are shown as median and range. MAIN RESULTS: Median age of BA patients was 2 (1-6) months. Hepatic HGF and C-met staining scores of BA patients were higher than those of non-cholestatic patients (P < 0.0001). There was a correlation between HGF and C-met staining scores (spearman r = 0.77, P < 0.0001). However, there was no association between their expression and early outcome at 6 months post-op. Mean follow-up time was 68.6 months. Survival analysis revealed that native liver survival at 1 year and 3 years were 88% and 77%, respectively. Additionally, 82.6% (19/23) of patients in the low-HGF group survived with native liver, compared with 66.7% (10/15) of those in high-HGF group (P = 0.436). For C-met expression, 78.6% (22/28) of low-score and 70% (7/10) of high score groups survived with native liver (P = 0.673). CONCLUSIONS: Strong expression of hepatic HGF and its receptor in BA patients was demonstrated. However, the expression was not associated with the early outcome and native liver survival. These results suggest that HGF involved in the liver pathology of BA but its expression cannot be used as a prognostic indicator. Small sample size of patients was a main limitation. Further studies are warranted to validate our findings.

Overexpression of Epstein-Barr virus-encoded latent membrane protein-1 (LMP-1) in oral squamous cell carcinoma.

BACKGROUND: As oral cavity is the main location of Epstein-Barr virus (EBV) latency and shedding, and as EBV-encoded latent membrane protein-1 (LMP-1) has a crucial role in cell transformation, association between EBV infection, LMP-1 expression and oral malignancy is of interest. Although EBV DNA has been detected in oral squamous cell carcinoma (OSCC), studies on LMP-1 expression in OSCC and oral potentially malignant disorders are scarce and still controversial. This study aimed to evaluate the expression of LMP-1 in OSCC and oral leukoplakia (OL). METHODS: Biopsy specimens of 36 OSCC, 69 OL with and without dysplasia and 10 normal oral mucosa were assessed for the expression of LMP-1 using immunohistochemistry. In each case, at least 1000 cells were counted. Cells with staining were considered positive, classified by location as nuclear, cytoplasmic and nuclear plus cytoplasmic staining. Percentage of positive cells at different locations and of total positive cells were determined. For statistical analysis, SPSS version 21 was used. Statistical significance was considered at p < 0.05. RESULTS: LMP-1 was expressed in all studied specimens. In terms of percentage of total positive cells, LMP-1 expression was higher from normal mucosa (26.36%), OL without dysplasia (28.03%), OL with dysplasia (34.15%), to the significantly highest, (59.67%) in OSCC. In addition, cells with nuclear staining alone, cytoplasmic staining alone and cells with nuclear plus cytoplasmic staining were significantly higher in OSCC compared to those of normal mucosa, OL with and without dysplasia. CONCLUSIONS: LMP-1 was overexpressed in OSCC. Our analysis on subcellular localization of LMP-1 in OSCC revealed prominent distinguished pattern, cytoplasmic distribution. Further studies in cell lines and animals are required to clarify the association between this EBV-encoded proteins and oral carcinogenesis.

Expression of cdk6 in head and neck squamous cell carcinoma.

OBJECTIVE: Cdk6 is a key regulator during the G1/S cell cycle transition. Aberrant expression of cdk6 protein has been observed in many cancer types. However, little is known about the expression of cdk6 in head and neck squamous cell carcinoma (HNSCC) and its clinical significance. This study evaluated the expression of cdk6 in HNSCC and analyzed the relationship between cdk6 expression and clinicopathological parameters of HNSCC. MATERIALS AND METHODS: Expression of cdk6 was immunohistochemically investigated in 98 HNSCCs. Nuclear and cytoplasmic positive cells were counted separately. Data were presented as the percentage of positive cells. The correlation between the percentage of positive cells and clinicopathological factors was determined. RESULTS: Nuclear and cytoplasmic staining for cdk6 were detected in 91 cases and 97 cases, respectively. A significant correlation was found only between the percentage of nuclear positive cells and T classification (p value = 0.0410). Tumors with high nuclear cdk6-positive cells showed a linear trend toward advanced tumor status (p value = 0.0064). CONCLUSIONS: Cdk6 was highly expressed in HNSCC. Tumors with high nuclear cdk6 expression tended to have advanced tumor status. These results suggest that cdk6 plays a vital role in HNSCC and is involved in tumor progression of this cancer. CLINICAL RELEVANCE: An increased nuclear cdk6 expression is an unfavorable factor for HNSCC. Cdk6 may serve as a therapeutic target in this cancer.

Aberrant expression of p-Smad3 in oral carcinogenesis.

OBJECTIVE: Smads are the keys of transforming growth factor ß (TGFß) signaling cascade and play a crucial role in many cancers. Once TGFß receptors are activated, Smad2 and Smad3 are phosphorylated and form complexes with Smad4. These complexes translocate from the cytoplasm to the nucleus where they regulate the target genes. The subcellular localization of phosphorylated Smad3 (p-Smad3) in oral carcinogenesis has never been reported. This study investigated the subcellular distribution of p-Smad3 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) with and without dysplasia. MATERIALS AND METHODS: Expression of p-Smad3 was immunohistochemically examined in 150 samples including OSCC, OL with and without dysplasia, and normal mucosa (NM). Cytoplasmic and nuclear positive cells were counted separately. The results were present as the frequency of positive cases. RESULTS: Cytoplasmic and/or nuclear staining for p-Smad3 was detected. The frequency of cytoplasmic expression in OL with dysplasia was significantly higher than that in NM. The numbers of cytoplasmic expression and cytoplasmic plus nuclear expression in OSCC were significantly higher than those in NM and OL with and without dysplasia. CONCLUSIONS: The overexpression of cytoplasmic p-Smad3 in OL with dysplasia and in OSCC suggests that p-Smad3 is in the nonfunctional state. Thus, the growth inhibitory effect of p-Smad3 is diminished during oral carcinogenesis. The cytoplasmic plus nuclear staining of p-Smad3 was aberrant in OSCC. CLINICAL RELEVANCE: The cytoplasmic staining of p-Smad3 may serve as a marker for oral premalignant lesions whereas the cytoplasmic plus nuclear staining of p-Smad3 may serve as a marker for OSCC.

Oral and maxillofacial lesions in a Thai pediatric population: a retrospective review from two dental schools.

OBJECTIVE: To determine the prevalence of oral and maxillofacial lesions in a Thai pediatric population. MATERIAL AND METHOD: Oral biopsy records from pediatric patients between the ages of 0 and 15 years in the files ofFaculty of Dentistry, Mahidol University, and the files of Faculty of Dentistry, Khon Kaen University were reviewed. The patients were divided into three age groups, including 0 to 5, 6 to 10, and 11 to 15 years. Excluding the diagnosis of normal tissues, the oral and maxillofacial lesions were classified into nine categories. RESULTS: Of 13,050 biopsied oral and maxillofacial lesions, 1,389 cases (10.6%) came from pediatric patients. The largest number of lesions was odontogenic cysts and tumors, followed by inflammatory and reactive lesions, and salivary gland pathology The top ten most prevalent lesions contributed 73% of all oral biopsies. The most common lesion was dentigerous cyst, followed by mucocele and pyogenic granuloma. CONCLUSION: The vast majority of oral diseases in children were benign and related to either developmental or tissue reaction, while malignant lesions were found in a very small proportion of all oral biopsies.

Preliminary Study on the Expression of CLLD7 and CHC1L Proteins in Oral Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to preliminarily evaluate the expression of two putative tumor suppressor proteins, including chronic lymphocytic leukemia deletion gene 7 (CLLD7) and chromosome condensation 1-like (CHC1L) proteins in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Expression of CLLD7 and CHC1L proteins was analyzed in 19 OSCC and 12 normal oral mucosa (NOM) using immunohistochemistry. The percentage of positive cells and intensity of staining were semiquantitatively assessed and expressed with an immunoreactive score. The number of positive cells at various subcellular localizations was evaluated and presented in percentages. The immunoreactivity scores and percentages of positive cells at various localizations were compared between the normal and OSCC groups with statistical significance at p-value less than 0.05. RESULTS: According to immunohistochemical analysis, the immunoreactivity scores for both CLLD7 and CHC1L were higher in NOM than those of OSCC. Analysis of CLLD7 localization revealed predominant nuclear staining at basal and parabasal areas in NOM, whereas more cytoplasmic staining was observed in OSCC. For CHC1L, nuclear staining was prominent in NOM. In contrast, significantly increased plasma membrane staining was detected in OSCC. CONCLUSION: The expression of CLLD7 and CHC1L proteins was reduced in OSCC. Alterations in the subcellular localization of these two proteins in OSCC were also demonstrated. These preliminary results suggest that CLLD7 and CHC1L are aberrantly expressed in OSCC. The precise mechanisms of these putative tumor suppressor proteins in OSCC require future studies.

Expression of CLLD7 and CHC1L Proteins in Oral Epithelial Dysplasia in a Group of Thai Patients.

OBJECTIVES: Previous study showed aberrant CLLD7 and CHC1L protein expression in oral squamous cell carcinoma (OSCC) compared to normal oral mucosa (NOM). This study aimed to evaluate the expression of these proteins in oral epithelial dysplasia (OED). MATERIALS AND METHODS: Forty specimens of OED and 11 NOM were used. The expression of CLLD7 and CHC1L was determined by immunohistochemistry. In each case, at least 1000 cells were counted. Presence of nuclear, cytoplasmic, and/or membrane staining of CLLD7 and CHC1L were considered positive. Percentages of total positive cells and positive cells at different locations were recorded. SPSS version 18 was used to compare variation between groups with statistical significance at p<0.05. RESULTS: No significant differences in the percentages of total positive cells of CLLD7 and CHC1L were found between NOM and all grades of OED. Nevertheless, there were significant differences in subcellular staining of these two proteins. In CLLD7, the nuclear staining of the moderate and the severe OED groups was significantly lower than that of the NOM group (p<0.05). The percentages of membrane staining of CHC1L in moderate and severe OED were significantly higher than that of NOM (p<0.001). In addition, the nuclear staining of CHC1L in each grade of OED was significantly lower than that of NOM (p<0.05). CONCLUSION: The subcellular mislocalization of CLLD7 and CHC1L in OED suggests that the expression of these potential tumor suppressor proteins might be dysregulated during the dysplastic process. The distinct membrane staining of CHC1L observed in OED but not in NOM is a useful characteristic that can be used to separate OED from NOM. Thus, CHC1L may be a good marker to assist in the diagnosis of OED.

Diagnostic potential of Type VII Collagen during oral carcinogenesis.

Type VII collagen (Col7) is a major component of anchoring fibrils. Col7 plays a role in tumor development and aggressiveness of cutaneous squamous cell carcinoma of recessive dystrophic epidermolysis bullosa. However, the role of Col7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) remains largely unknown. To elucidate the role of Col7 and its diagnostic potential during oral carcinogenesis. Col7 expression was immunohistochemically studied in 254 samples, including normal oral mucosa (NM), OL without dysplasia, OL with dysplasia, and OSCC. The correlation between Col7 expression and clinicopathologic parameters of OSCC was also determined. Col7 was present as a linear deposit at the basement membrane of NM, OL without dysplasia and OL with dysplasia, and at the tumor-stromal junction around tumor islands in OSCC. Discontinuity of expression was frequently observed in OL with dysplasia and OSCC. OSCC had the significantly lowest Col7 expression (p<0.0001). Compared with OL without dysplasia, OL with dysplasia showed significantly reduced Col7 expression. Patients in clinical stage 4 with positive nodes had low Col7 expression compared with those in clinical stage 1 and negative nodes, respectively. Loss of Col7 is associated with tumorigenesis and aggressiveness in OSCC. A significantly reduced Col7 expression in OSCC implies that Col7 may be a useful marker for diagnosis and therapeutic targets.

Epithelial and fibroblast SPARC expression patterns in oral leukoplakia and oral squamous cell carcinoma.

OBJECTIVE: This study evaluated and compared the expression of secreted protein acidic and rich in cysteine (SPARC) in epithelial cells and fibroblasts of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) using normal oral mucosa as a control. STUDY DESIGN: The expression of SPARC was determined in samples of normal oral mucosa (n = 12), OL without dysplasia (n = 31), OL with dysplasia (n = 54), and OSCC (n = 69) using immunohistochemistry. The percentage of positive cells in epithelial cells and fibroblasts was independently evaluated. RESULTS: Epithelial SPARC was found in 33.3%, 35.5%, 25.9%, and 66.7% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. Fibroblast SPARC was found in 50.0%, 29.0%, 46.3%, and 84.1% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. OSCC had higher epithelial and fibroblast SPARC expression than normal oral mucosa, OL without dysplasia, and OL with dysplasia (P < .05). No significant differences were observed in epithelial and fibroblast SPARC among normal oral mucosa or OL with and without dysplasia. CONCLUSION: Overexpression of epithelial and fibroblast SPARC was observed in OSCC but not in OL, suggesting that SPARC is involved in the late stage of oral carcinogenesis.

Potential Role of Epstein-Barr Virus in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Scoping Review.

Though the oral cavity is anatomically proximate to the nasal cavity and acts as a key reservoir of EBV habitation and transmission, it is still unclear whether EBV plays a significant role in oral carcinogenesis. Many studies have detected EBV DNA in tissues and exfoliated cells from OSCC patients. However, very few studies have investigated the expression of functional EBV proteins implicated in its oncogenicity. The most studied are latent membrane protein 1 (LMP-1), a protein associated with the activation of signalling pathways; EBV determined nuclear antigen (EBNA)-1, a protein involved in the regulation of gene expression; and EBV-encoded small non-polyadenylated RNA (EBER)-2. LMP-1 is considered the major oncoprotein, and overexpression of LMP-1 observed in OSCC indicates that this molecule might play a significant role in oral carcinogenesis. Although numerous studies have detected EBV DNA and proteins from OSCC and oral potentially malignant disorders, heterogeneity in methodologies has led to discrepant results, hindering interpretation. Elucidating the exact functions of EBV and its proteins when expressed is vital in establishing the role of viruses in oral oncogenesis. This review summarises the current evidence on the potential role of EBV in oral oncogenesis and discusses the implications as well as recommendations for future research.

Overexpression of cdk4 and p16 in oral lichen planus supports the concept of premalignancy.

BACKGROUND: Cell cycle arrest and increased cell proliferation have been demonstrated in oral lichen planus (OLP). This study evaluated the expression of cdk4, cdk6 and p16, important proteins in the G1 phase, in OLP and compared the expression of these proteins of OLP with those of normal mucosa. METHODS: Expression of cdk4, cdk6 and p16 were investigated in 23 OLP and 10 normal mucosae using immunohistochemistry technique. Positive cells were counted and presented as a percentage of positive cells. RESULTS: Expression of cdk4, cdk6 and p16 was observed in 3/10 (30%), 1/10 (10%) and none of normal mucosa, respectively. Expression of cdk4, cdk6 and p16 was detected in 18/23 (78.3%), 8/23 (34.8%) and 15/23 (65.2%), of OLP, respectively. The numbers of cdk4 and p16 positive cases of OLP were significantly higher than normal mucosa. In normal mucosa, the averages of the percentage of positive cells for cdk4 and cdk6 staining were 1.48 and 0.18, respectively. In OLP, the averages of the percentage of positive cells for cdk4, cdk6 and p16 staining were 2.73, 1.06 and 2.24, respectively. The percentage of cdk4-positive cells of OLP was significantly higher than those of normal mucosa group. CONCLUSION: Oral lichen planus demonstrated overexpression of cdk4 and p16, but not cdk6, suggesting that epithelial cells in OLP are in the hyperproliferative state and in cell arrest. Altered expression of cdk4 and p16 provides evidence of the malignant potential in OLP.

Non-endodontic periapical lesions clinically diagnosed as endodontic periapical lesions: A retrospective study over 15 years.

BACKGROUND: This study aimed to provide the frequency and demographic data of non-endodontic periapical lesions clinically misdiagnosed as endodontic periapical lesions from a Southeast Asian population over a 15-year period. MATERIAL AND METHODS: A retrospective study was conducted from departmental archives between 2005 and 2019. Cases clinically diagnosed as endodontic periapical lesions were retrieved. Then, cases with a histopathological diagnosis of non-endodontic periapical lesion were selected. Demographic data of non-endodontic periapical lesions were recorded. Radiographic features of cases with available radiographs were analyzed. RESULTS: Of 1,566 cases clinically diagnosed as endodontic periapical lesion, 157 cases received a histopathological diagnosis of non-endodontic origin. Eighteen different histopathological diagnoses were identified. The most frequent lesion was dentigerous cyst (n= 51, 32.48%) followed by odontogenic keratocyst (n=31, 19.75%), nasopalatine duct cyst (n=18, 11.46%) and ameloblastoma (n=15, 9.56%). Three cases of malignant tumors, including adenoid cystic carcinoma, mucoepidermoid carcinoma, and metastatic papillary thyroid carcinoma were observed. CONCLUSIONS: Non-endodontic periapical lesions constituted 10.03% of cases clinically diagnosed as endodontic periapical lesions. Histopathological examinations of non-endodontic periapical lesions revealed a variety of lesions ranging from foreign body reaction, cysts, fibro-osseous lesions, benign tumors and primary or metastatic malignant tumors. Of clinical significance is that some non-endodontic periapical lesions had different treatment modalities and prognoses compared with endodontic lesions. Therefore, dentists must be aware that periapical radiolucent lesions are not always a consequence of pulpal necrosis. Key words:Ameloblastoma, dentigerous cyst, endodontic periapical lesions, non-endodontic periapical lesions, odontogenic keratocyst.

Intraoral Oncocytic Mucoepidermoid Carcinoma - A Rare Case Report and Review of the Literature.

Rationale: Oncocytic mucoepidermoid carcinoma (OMEC) is a rare variant of mucoepidermoid carcinoma (MEC). The parotid gland is the most common site of OMEC, whereas intraoral OMEC is infrequent. Patient Concerns: A 55-year-old male presented with an asymptomatic mass at the palate for 20 years. Diagnosis: Incisional biopsy showed classic MEC. Treatment: The patient underwent partial maxillectomy under general anaesthesia. The excised specimen revealed sheets of oncocytes additional to the tumour cells found in the incisional biopsy. Additional special stain and immunohistochemical stain confirmed the diagnosis of OMEC. Outcomes: The patient was followed up for 3 years with no recurrence. Take-away Lessons: The diagnosis of OMEC needs to be differentiated from other salivary gland tumours containing oncocytes. Moreover, the conventional grading system applied to OMEC may not correlate with their behavior and may need further review.

Diagnostic Value of Cytokeratin 17 during Oral Carcinogenesis: An Immunohistochemical Study.

BACKGROUND: Little is known about the role of cytokeratin 17 (CK17) during oral carcinogenesis. CK17 expression in oral leukoplakia (OL), the most encountered oral potentially malignant disorders and oral squamous cell carcinoma (OSCC), remains very limited. To determine the role of CK17 during oral carcinogenesis and its potential diagnostic marker in oral premalignant and malignant lesions, this study evaluated CK17 expression in OL without dysplasia, OL with dysplasia, and OSCC. CK17 expression in these tissues was compared with those of normal oral mucosa (NOM). Additionally, the relationship between CK17 expression and clinicopathologic factors of OSCC was investigated. METHODS: CK17 expression was evaluated in 186 samples consisting of 12 NOM, 33 OL without dysplasia, 58 OL with dysplasia, and 83 OSCC using immunohistochemistry. The proportion of positively immunostained cells was evaluated and scored. RESULTS: CK17 was expressed in 8.3%, 54.5%, 74.1%, and 90.4% of NOM, OL without dysplasia, OL with dysplasia, and OSCC, respectively. NOM had a significantly lower CK17 score than OL with dysplasia (p=0.0003) and OSCC (p < 0.0001). A significant association between CK17 expression and histopathologic differentiation of OSCC was found. Tumors with well differentiation had high CK17 expression compared with those of moderate and poor differentiation. CONCLUSION: CK17 was overexpressed in OL with dysplasia and OSCC, suggesting that CK17 plays a pivotal role in the development of premalignant lesions and OSCC. Of clinical significance, CK17 may be a good diagnostic marker for oral premalignant lesions and OSCC. Additionally, CK17 could be used as an objective tool to classify histopathologic grade in OSCC. The findings that CK17 expression is high in OSCC but low in NOM imply that CK17 may serve as a potential therapeutic target for OSCC.

Odontogenic keratocyst and ameloblastoma: radiographic evaluation.

OBJECTIVES: To describe the radiographic features of odontogenic keratocysts (OKCs) and ameloblastomas and to compare the radiographic findings between these 2 lesions. METHODS: Radiographs of OKCs and ameloblastomas were retrospectively reviewed. Location, border, shape, association with impacted tooth, tooth displacement, root resorption, and bone expansion were evaluated. Chi-squared or Fisher's exact tests were used for statistical analysis. A p value < 0.05 was considered to indicate statistical significance. RESULTS: One hundred OKCs and 101 ameloblastomas were reviewed. The ratios of maxilla to mandible were 1:1.4 and 1:9.1 in OKCs and ameloblastomas, respectively. All evaluated features significantly differed between OKCs and ameloblastomas (p ≤ 0.001). Most OKCs showed smooth border (60%) and unilocular shape (82%), while most ameloblastomas showed scalloped border (77.2%) and multilocular shape (68.3%). Association with impacted tooth was found in 47% of OKCs and 18.8% of ameloblastomas. Adjacent tooth displacement was found in 33.7% of OKCs and 55.8% of ameloblastomas. Root resorption was more common in ameloblastomas (66.7%) than in OKCs (7%). Bone expansion was also more common in ameloblastomas (96.3%) than in OKCs (63.6%). CONCLUSION: A unilocular radiolucent lesion with smooth border, no adjacent tooth displacement, no root resorption and causing mild or no bone expansion is suggestive of an OKC rather than an ameloblastoma.

Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions.

BACKGROUND: Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC). This study investigated the expression of these two proteins in OSCC and premalignant lesions including oral leukoplakia (OL) with and without dysplasia and determined if alterations in the expression of these two proteins could be used as markers of malignant transformation. METHODS: Expressions of cdk4 and cdk6 were evaluated in 61 samples including OSCC, OL with and without dysplasia and normal oral mucosa using immunohistochemistry method. Nuclear staining of the keratinocytes was considered positive and the percentage of positive cells was calculated. RESULTS: Expression of cdk4 was found in 11/15 (73.33%) OSCC, 13/14 (92.85%) OL with dysplasia, 13/20 (65%) OL without dysplasia and 3/12 (25%) normal mucosa. Expression of cdk6 was detected in 9/15 (60%) OSCC, 3/14 (21.43%) OL with dysplasia, 5/20 (25%) OL without dysplasia and 1/12 (8.33%) normal mucosa. In cdk4 stained specimens, the frequency of positive cases and the percentage of positive cells in normal mucosa was significantly lower than OL with dysplasia and OSCC. For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than OSCC. CONCLUSIONS: Overexpressions of cdk4 and cdk6 were observed in OSCC, indicating that these two proteins play a crucial role in OSCC. The aberrant expression of cdk4 was found in OL with dysplasia, suggesting that cdk4 may be involved in the early event of carcinogenesis.

Identification of Novel Candidate Biomarkers for Oral Squamous Cell Carcinoma Based on Whole Gene Expression Profiling.

This study aimed to determine the whole gene expression profiles and to ascertain potential biomarkers for 22 oral squamous cell carcinoma (OSCC) among Thai patients using the Illumina Human HT-12, V4.0 Expression BeadChip array. Result indicated 2,724 differential expressed genes composed of 1,560 up-regulated and 1,164 down-regulated genes (unpaired t-test, p-value <0.05; fold change ≥2.0 and ≤2.0). The top 9 up-regulated genes were validated in 39 OSCC cases using TaqMan real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. Among these, the up-regulation of peptidase inhibitor 3 (PI3) and keratin 17 (KRT17) genes was harbored in all 39 OSCC patients (100%). Likewise, statistical analysis indicated that gene expression in 8 selective genes including keratin 16 (KRT16), keratin 14 (KRT14), keratinocyte differentiation-associated protein (KRTDAP), keratin 6B (KRT6B), PI3, S100 calcium binding protein A7 (S100A7), stratifin (SFN) and keratin 5 (KRT5) was significantly associated with well differentiated OSCC (p-value <0.05). Moreover, high level of KRT17 protein was significantly associated with well differentiated OSCC compared to moderately OSCC (p-value = 0.041). Notably, using nested-PCR analysis indicated all OSCC cases in this study were HPV-free. Especially, KRTDAP, PI3, SFN mRNA expression were first reported among patients with OSCC. Conclusion, the whole transcript expression study and TaqMan real-time qRT-PCR assay were relevant regarding the increase in gene expression in OSCC. In addition, the up-regulation of PI3 and KRT17 might constitute potential candidate molecular biomarkers to diagnose patients with OSCC.