Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma / 国际口腔科学杂志·英文版

Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

Primary sinonasal mucosal melanoma simulated as cystic lesions: a case report

Sinonasal mucosal melanoma (SNMM) in the maxillary sinus is a rare disease condition. Compared to oral mucosal melanoma, SNMM has a bulky, exophytic, and polypoid appearance, is weakly pigmented, and associated with unspecific symptoms. Due to these features, SNMM in the maxillary sinus has been misdiagnosed as nasal polyps and chronic sinusitis. In this case report, we described SNMM occurring in the right maxillary sinus simulated as a cystic or benign lesion. Cortical bone thinning and expansion were observed around the mass. The excised soft mass was encapsulated and weakly pigmented. The mass was clearly excised and covered with a pedicled buccal fat pad graft. Diagnosis using immunohistochemistry with S-100 and homatropine methylbromide-45 (HMB-45) is critical for proper treatment.

Primary sinonasal mucosal melanoma simulated as cystic lesions: a case report

Sinonasal mucosal melanoma (SNMM) in the maxillary sinus is a rare disease condition. Compared to oral mucosal melanoma, SNMM has a bulky, exophytic, and polypoid appearance, is weakly pigmented, and associated with unspecific symptoms. Due to these features, SNMM in the maxillary sinus has been misdiagnosed as nasal polyps and chronic sinusitis. In this case report, we described SNMM occurring in the right maxillary sinus simulated as a cystic or benign lesion. Cortical bone thinning and expansion were observed around the mass. The excised soft mass was encapsulated and weakly pigmented. The mass was clearly excised and covered with a pedicled buccal fat pad graft. Diagnosis using immunohistochemistry with S-100 and homatropine methylbromide-45 (HMB-45) is critical for proper treatment.

Survivin, Possible Marker and Prognostic Factor in Oral Squamous Cell Carcinomas

Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clinico-pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients' clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.

Effects of the Er,Cr:YSGG laser on bone bed preparation with various laser tips / 대한치과보철학회지

STATEMENT OF PROBLEM: Preparation of implant beds with lasers is considered a safe and reliable method, but the accuracy of this technique has not been examined. PURPOSE: The purpose of this study was to evaluate the accuracy and effectiveness of implant bed preparation using an Er,Cr:YSGG laser. MATERIAL AND METHODS: An Er,Cr:YSGG laser was applied to pig rib bone. The laser was employed at a 5.75 W power setting, 30 Hz/sec pulse repetition, and 70 micro sec pulse duration with 50 % water and 60% air spray. According to laser tips the groups were divided as follows; Group 1: paralleled - shaped sapphire tip (0.6 mm phi), Group 2: paralleled - shaped zirconia tip (0.6 mm phi), Group 3: tapered sapphire tip (0.4 mm phi). The Er,Cr:YSGG laser tip was separated by 1 mm from the bone and applied for 15 seconds in a non-contact mode. After the application, the bone was sectioned for specimens. Histologic measurements were determined by computerized morphometry. The length of the prepared bone surface was measured and the width of the entrance was measured. The results were analyzed with one-way ANOVA (P<0.05). RESULTS: The prepared length of group 3 was longer than that of group 2. The prepared bone width was larger than the width of the laser tip in every group. Additional bone removal was observed adjacent to the prepared area and displayed an irregular surface. CONCLUSION & DISCUSSION: Different cutting effects were observed according to the laser tip, emphasizing the importance of proper tip selection in the clinical setting. This preliminary study supported the existence of hydrokinetic effects.

Analysis of 67 malignant salivary gland tumors in Korean population

Malignant salivary gland tumor is rare neoplasm. In Korean population, retrospective study of malignant salivary gland tumor has not been performed. We analyzed 67 cases of malignant salivary gland tumors from 2001 to 2005 in Seoul National University Dental Hospital in Seoul, Korea. The mean age is 51.7 and the male to female ratio is 1:1.39. The most affected site is the palate. Histologically, the tumors were classified as adenoid cystic carcinoma(34.4%), mucoepidermoid carcinoma(31.3%), adenocarcinoma, NOS(11.9%), polymorphous low grade adenocarcinoma(3.0%), salivary duct carcionoma(6.0%), carcinoma ex pleomorphic adenoma(4.5%), myoepithelial carcinoma(4.5%), epithelial-myoepithelial carcinoma(1.5%), cyatadenocarcinoma(1.5%) and adenosquamous carcinoma(1.5%).

Inactivation patterns of p16/INK4A in oral squamous cell carcinomas

The p16/INK4A is one of the major target genes in carcinogenesis and its inactivation has frequently been reported in other types of tumors. The purpose of this study is to evaluate inactivation patterns of p16/INK4A in oral squamous cell carcinoma. Six different oral cancer cell lines, SCC-4, SCC-9, SCC-15, SCC-25, KB, and SNUDH- 379 were examined for inactivation of p16/INK4A genes. In the analysis of p16/INK4A gene inactivation, PCR amplification, direct sequencing, and methylation-specific PCR methods were adopted for evaluation of homozygous deletion, point mutation, and promoter hypermethylation, respectively. Homozygous deletion was detected in SCC-25 and SCC-9. SCC-15 showed hypermethylated promoter region within p16/INK4A gene. It is suggestive in the present study that inactivation patterns of p16/INK4A were mainly homozygous deletion, promoter methylation rather than point mutation in oral squamous cancer cell lines, so treatment modalities of oral squamous cell carcinoma should be focused on these types of inactivation.

VEGF Expression and Microvessel Density in Oral Squamous Cell Carcinomas

Angiogenesis is an essential process in tumor growth and metastasis. VEGF has been considered a leading candidate inducing tumor angiogenesis. VEGF expression was significantly correlated with clinical stage, lymph node matastasis, and prognosis of cancers of various parts of body. However, little has been known about the correlation between VEGF expression and clinicopathologic parameters in oral squamous cell carcinoma. The aim of this study was to correlate VEGF expression with the clinicopathological parameters and microvessel density. Forty six oral squamous cell carcinomas were analyzed using immunohistochemical method with primary antibodies to VEGF and CD31. VEGF expression was detected in 33 (71.7%) of the 46 cases. The microvessel density was significantly correlated with VEGF expression (P=0.002). There was no correlation between microvessel density and tumour size, clinical stage, and lymph node metastasis, respectively. VEGF expression did not correlate with the histological grade of tumour differentiation, tumour size, and clinical stages. The VEGF-positive rate seemed to be higher in patients with cervical lymph nodal metastasis than in those without it, but it was not statistically significant. In conclusion, the overexpression of VEGF in the oral squamous cell carcinoma seemed to be associated with a more aggressive course of the disease. Further study is necessary to define the role of VEGF in oral squamous cell carcinoma.

Expression of Matrix Metalloproteinase-2 and -9 in Oral Squamous Cell Carcinomas in Relation to the Histologic Invasiveness and Cellular Differentiation

A poor prognosis of oral squamous cell carcinoma (SCC) is partly due to the invasiveness and metastasis of the tumor. A key element in tumor invasion and metastasis in the degradation of extracellular matrix is matrix metalloproteinases (MMPs). This study was performed to determine the expression of MMP-2 and MMP-9 of oral SCCs with regard to the histologic invasiveness and differentiation in 5 normal oral mucosa and 36 oral SCCs. The histologic invasiveness of oral SCCs were classified into 4 grades. The differentiation of oral SCCs was divided into 3 grades. The streptavidin-biotin immunohistochemical staining, using MMP-2 and MMP-9 monoclonal antibodies, was performed to determine the expression of MMP-2 and MMP-9. The expression of MMP-2 was positive in 6 of 17 oral SCCs with weak invasiveness and was positive in 7 of 19 oral SCCs with strong invasiveness. The MMP-2 expression did not increase significantly with respect to the invasiveness of oral SCCs (P>0.05). The expression of MMP-9 was strongly positive in 6 out of 17 SCCs with weak invasiveness and was strongly positive in 14 of 19 SCCs with strong invasiveness. The MMP-9 expression increased significantly with respect to the invasiveness of oral SCCs; the stronger the expression, the stronger the invasiveness (P<0.05). The expression of MMP-9 was in 57.9% of well differentiated SCCs, 57.1% of moderately differentiated ones, and 33.3% of poorly differentiated SCCs. The expression of MMP-2 and MMP-9 did not increase significantly with respect to the histologic differentiation. We conclude that with respect to the invasiveness, the MMP-9 expression increases significantly in oral SCCs but the MMP-2 expression does not; and that with respect to the histologic differentiation, their expressions do not increase significantly. These results suggeste that MMP-9 can be used as a tool to evaluate the invasiveness of oral SCCs.

Evaluation of Prognostic Significance of AgNORs and PCNA during 9,10-dimethyl-1,2-benzantracene(DMBA)-induced Hamster Buccal Pouch Carcinogenesis

The purpose of this study is to evaluate the prognostic significance of argyrophilic nucleoalr organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) by using DMBA hamster buccal pouch carcinogenesis which provides a good experimental model in reproducing steps from precancerous lesions to invasive squamous cell carcinomas. The buccal pouches of 50 Syrian hamsters were applied with 0.5% DMBA in mineral oil three times a week to reproduce various lesions from precancerous ones such as hyperkeratosis or epithelial dysplasia to invasive squamous cell carcinomas. Their sections were stained with H & E, and silver colloid, and processed immunohistochemically by being applied with monoclonal antibody to PCNA. The histopathologic examainations were done and the counts of AgNORs were evaluated. The PCNA labelling indices on each lesions were evaluated. The correlation between histopathological grades and counts of AgNORs or PCNA labelling indices were evaluated. The number of AgNORs was 2.22+/-0.22 in control group, 3.46+/-0.72 in carcinoma in situ (CIS), 3.78+/-0.63 in squamous cell carcinoma (SCC), respectively. AgNORs significantly increased in severe epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The PCNA Labeling Index (LI) was 39.47+/-6.68% in control group, 79.61+/-4.14% in CIS, and 85.43+/-6.25% in SCC, respectively. PCNA LI also significantly increased in epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The number of AgNORs, AgNOR area, and PCNA LI slightly increased in the advancing front than in the center of SCC, but, it was not statistically significant. It appeared that there were a good correlation between the number of AgNORs and PCNA LI (Pierson correlation coefficient : 0.649, P<0.001). These results suggested that the number of AgNORs and the PCNA LI could be useful markers for evaluating the risk of malignant transformation and prognosis of SCC. It was thought that the clinical usefulness of these markers should be verified by using human tissue specimens.