Marker For Oral Squamous Cell Carcinoma Research Articles

ROLE OF MYOFIBROBLASTS IN THE PRIMARY LESIONS AND LYMPH NODE METASTASIS OF ORAL SQUAMOUS CELL CARCINOMA

physiologic and pathologic processes such as wound healing and tumorigenesis, respectively. Tumor cells work in close coordination with stromal elements from its stage of emergence to metastasis. Myofibroblasts are important stromal cells that play a crucial role in carcinogenesis due to its ability to modify the extracellular matrix. Alpha smooth muscle actin (α-SMA) is regarded as the most widely used biomarker for identifying myofibroblasts. The presence of myofibroblasts has been demonstrated in various malignant lesions. However, the number of studies evaluating their role in oral squamous cell carcinoma (OSCC) remains limited.OBJECTIVES: The present study aimed to assess the presence and distribution patterns of myofibroblasts in OSCC primary tissues according to histological grade, as well as to determine its correlation with metastasis in regional lymph nodes (LNs).MATERIAL AND METHODS: Immunohistochemical study using the α-SMA antibody was done on 30 OSCC cases (15 cases with LN metastasis and 15 cases without LN metastasis) and 15 normal oral mucosal tissues.RESULTS: Most of OSCC tissues showed positive immunoreactivity to α-SMA, while normal tissues were immune-negative. The expression of α-SMA was significantly higher in the OSCC with LN metastasis than OSCC without LN metastasis (P < 0.05). Conversely, there was no significant correlation with the histological grades of OSCC.CONCLUSION: α-SMA could be used as a monitory marker in OSCC.

Immunohistochemical Expression of Five Protein Combinations Revealed as Prognostic Markers in Asian Oral Cancer.

Oral squamous cell carcinoma (OSCC) has a high mortality rate (∼50%), and the 5-year overall survival rate is not optimal. Cyto- and histopathological examination of cancer tissues is the main strategy for diagnosis and treatment. In the present study, we aimed to uncover immunohistochemical (IHC) markers for prognosis in Asian OSCC. From the collected 742 synthetic lethal gene pairs (of various cancer types), we first filtered genes relevant to OSCC, performed 29 IHC stains at different cellular portions and combined these IHC stains into 398 distinct pairs. Next, we identified novel IHC prognostic markers in OSCC among Taiwanese population, from the single and paired IHC staining by univariate Cox regression analysis. Increased nuclear expression of RB1 [RB1(N)↑], CDH3(C)↑-STK17A(N)↑ and FLNA(C)↑-KRAS(C)↑were associated with survival, but not independent of tumor stage, where C and N denote cytoplasm and nucleus, respectively. Furthermore, multivariate Cox regression analyses revealed that CSNK1E(C)↓-SHC1(N)↓ (P = 5.9 × 10–5; recommended for clinical use), BRCA1(N)↓-SHC1(N)↓ (P = 0.030), CSNK1E(C)↓-RB1(N)↑ (P = 0.045), [CSNK1E(C)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.000, rounded to three decimal places) and [BRCA1(N)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.020) were significant factors of poor prognosis, independent of lymph node metastasis, stage and alcohol consumption. An external dataset from The Cancer Genome Atlas HNSCC cohort confirmed that CDH3↑-STK17A↑ was a significant predictor of poor survival. Our approach identified prognostic markers with components involved in different pathways and revealed IHC marker pairs while neither single IHC was a marker, thus it improved the current state-of-the-art for identification of IHC markers.

A Reductionist Approach Using Primary and Metastatic Cell–Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis

Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher their role in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 63 lipids differentially abundant between LN1 cell– and SCC-9 cell–derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared with primary tumor–derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases and found that low abundance of seven ‘hub proteins’ in EVs from metastatic lymph nodes (ALDH7A1, CAD, CANT1, GOT1, MTHFD1, PYGB, and SARS) is correlated with reduced survival and tumor aggressiveness in patients with cancer. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis and which may potentially serve as prognostic markers in OSCC.

Immunoexpression of P16 and Ki 67 in oral squamous cell carcinoma: Association with clinicopathological parameters.

Background and Objectives: Oral squamous cell carcinoma (OSCC) is considered as a major health problem worldwide and has been associated with high recurrence rate and poor progno-sis. Advances in understanding of OSCC have not improved the outcome in their management significantly. Many studies have focused on the roles of biomolecular markers in OSCC. The use of p16 and Ki67 as biomarkers of biological behavior of oral squamous cell carcinoma is contro-versial. This study aimed to determine immunoexpression of P16 and Ki67 in oral squamous cell carcinoma and to evaluate their association with various clinicopathological parameters. Materials and Methods: Fifty cases of squamous cell carcinoma from different locations in the oral cavity were included in this cross sectional study. The cases were collected from Rizgary Teaching Hospital and Private Laboratories in Erbil city during a period of eight months from October 2018 to May 2019. The expression of p16 and Ki 67 were evaluated immunohistochem-ically; the findings were correlated with the age of the patients, gender, site of the tumor and grade of the tumor. Result: A total of 50 patients with oral squamous cell carcinoma were enrolled in this study the age ranged from 33 to 89 years, with a mean age ± SD of (64.24 ±12.01) years and more than half (52.0%) of them were males. Lower lip was the most common site of the tumor followed by upper lip and tongue (42.0%, 26.0% and 18.0%, respectively). Histopathological findings of the tumor showed that (54.0%) of the patients had moderately differentiated squamous cell carci-noma. However, (84.0%) of the patients showed negative expression of P 16, while Ki 67 ex-pression was positive among (76.0%) of them. No significant statistical association were found between immunoexpression of p16 and age, sex of patient, site of the tumor and grade of the tumor (P=0.67, P=0,095, P=0.696, P=0.454 respectively). No significant statistical association were found between immunoexpression of Ki67 and age, sex of patient, site of the tumor and grade of the tumor (P=0.637, P=0,411, P=0.353, P=1.00 respectively). Conclusion: in relation to the results obtained in this study no significant association were found between P16 and Ki 67 immunoexpression in oral squamous cell carcinoma with clinicopatho-logical parameters. Further researches have to be designed to better understand the role of p16 and Ki 67 in OSCC. Keywords: oral squamous cell carcinoma, immunoexpression, P16, Ki67.

Increased Expression of SHMT2 Is Associated With Poor Prognosis and Advanced Pathological Grade in Oral Squamous Cell Carcinoma.

This study focused on the expression of mitochondrial serine hydroxymethyltransferase (SHMT2) in oral squamous cell carcinoma (OSCC) and its correlation with clinical traits and the prognosis of OSCC patients. Immunochemical staining and Western blotting were used to quantify the expression of SHMT2 and related immune markers in OSCC. Using OSCC microarrays and The Cancer Genome Atlas (TCGA) database, we evaluated the association between SHMT2 and various clinical traits. We found that increased expression of SHMT2 was detected in OSCC and correlated with advanced pathological grade and recurrence of OSCC. By a multivariate Cox proportional hazard model, high expression of SHMT2 was shown to indicate a negative prognosis. In addition, in the OSCC microenvironment, increasing the expression of SHMT2 was associated with high expression levels of programmed cell death-ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain containing 6 (CMTM6), V-type immunoglobulin domain-containing suppressor (VISTA), B7-H4, Slug, and CD317. In the future, more effort will be required to investigate the role of SHMT2 in the OSCC microenvironment.

Tumor expression of miR-448 is a prognostic marker in oral squamous cell carcinoma

BackgroundPrognosis is poor for patients with malignant progression such as distant metastasis of oral squamous cell carcinoma (OSCC). Evidence indicates that miR-448 promotes the proliferation and inhibits apoptosis of OSCC cells. Therefore, we aimed to investigate the function of miR-448 to predict tumor progression and prognosis of OSCC.MethodsReal-time quantitative reverse transcription PCR was used to measure miR-448 expression in 221 pairs of OSCC tissues and the corresponding noncancerous tissues. Patients were diagnosed with OSCC from 2009 through 2011 at the Tianjin Medical University Cancer Institute and Hospital. Chi-squared tests were performed to assess the associations between miR-448 expression and clinicopathological parameters. Kaplan–Meier analysis was employed to evaluate the association of overall survival (OS) and disease-free survival (DFS) with miR-448 levels. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model.ResultsWe show here that miR-448 expression was significantly up-regulated in OSCC tissues compared with noncancerous tissues (P < 0.01). High miR-448 expression was significantly associated with advanced T stage (P = 0.001), lymph node metastasis (P = 0.007) and higher TNM stage (P = 0.009). Moreover, Kaplan–Meier and univariate analyses revealed that patients with high expression of miR-448 experienced significantly shorter OS and DFS. Furthermore, multivariate analysis demonstrated that miR-448 expression was an independent prognostic factor for OS (P = 0.004) and DFS (P = 0.002).ConclusionsOur present data suggests that miR-448 may play an important role in tumor progression and serves as a prognostic marker for OSCC. Further studies are required to assess the potential value of miR-448 to contribute to personalized treatment of OSCC.

MicroRNA-758 Regulates Oral Squamous Cell Carcinoma via COX-2

The present study is to examine the expression of microRNA (miRNA or miR)-758 in tumor tissues, blood, and serum from patients with oral squamous cell carcinoma (OSCC) and try to investigate its regulatory mechanism on OSCC. Twenty-eight OSCC patients and 36 healthy subjects were included in the study. Tumor tissues and tumor-adjacent tissues were collected from OSCC patients. Peripheral blood and saliva were collected from OSCC patients and healthy subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of mRNA and microRNA. Western blotting was carried out to measure protein expression in tissues, while ELISA was employed to determine protein content in serum and saliva. Dual luciferase reporter assay was used to identify the direct interaction between COX-2 mRNA and miR-758. COX-2 mRNA and protein expression was elevated in OSCC patients. In addition, expression of miR-758 was decreased in OSCC patients. miR-758 was able to bind with the 3′-UTR seed region of COX-2 mRNA to regulate its expression. The present study demonstrates that increased expression of COX-2 in tumors, serum, and saliva from OSCC patients is correlated with the decrease of miR-758 expression. miR-758 might regulate OSCC via COX-2 and can be used as a potential gene marker for OSCC.

Loss of S100A14 expression at the tumor-invading front correlates with poor differentiation and worse prognosis in oral squamous cell carcinoma.

We previously showed a tumor-suppressive function of S100A14 in oral squamous cell carcinoma (OSCC). This study aimed to examine the prognostic significance and differentiation-related function of S100A14 in OSCC. S100A14 expression was examined in 170 OSCCs from Norwegian and Nepalese populations using immunohistochemistry. Pro-differentiation function was investigated by overexpressing and silencing S100A14 expression in OSCC-derived cells. External transcriptomic datasets were used to validate association between S100A14 and differentiation markers in OSCC. Loss of S100A14 expression at the invading tumor fronts significantly correlated with poor differentiation and reduced 10-years survival of OSCC-patients. Multivariate Cox analysis identified S100A14 to be an independent prognostic factor. Modulation of S100A14 expression in OSCC-derived cells positively correlated with the expression of differentiation markers. Analysis of external datasets supported the pro-differentiation function of S100A14. These results indicate that S100A14 is a pro-differentiation protein and its expression might be useful as a prognostic marker in OSCC.

A Case-control Study Comparing and Correlating iNOS Expression among Various Clinicopathological Variants of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Immunohistochemistry Study.

ABSTRACTBackground and Objective:The role of inducible nitric oxide synthase (iNOS) has been implicated in various pathological processes including oral carcinoma. Oral premalignancy being its precursor lesion is also expected to show similar pattern. This study attempts to appraise the iNOS expression in various clinicopathological stages and grades of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC).Materials and Methods:A case-control study design was adopted for this study with a total sample of 90 subjects, distributed equally into the three study groups, namely controls, OL, and OSCC. Clinical staging and histopathological grading for both the case groups were performed. Representative tissue samples from all groups were obtained and studied for iNOS expression using immunohistochemistry (IHC). Data were presented in mean and percentages accordingly. Inferential analysis was performed using Kruskal–Wallis test, Mann–Whitney test, and Spearman rank correlation test.Results:Significant (P < 0.001) difference was observed among the groups, where 83.3% of OSCC and 73.3% of OL epithelial cells showed iNOS expression. The normal cells did not show up any expression. The expression was found to rise with the progressing clinical stages of OL (P < 0.05) and OSCC (P < 0.01). Similar pattern was observed with respect to advancing dysplasia in OL (P < 0.01) and cell differentiation in OSCC (P < 0.01). Significant positive correlation was found in clinicopathological categories of OL and OSCC. Considering the risk assessment, iNOS staining was found to be significantly raised in advanced cases of OSCC (P < 0.01) and high-risk cases of OL (P < 0.01).Conclusion:Increased expression of iNOS can be an early diagnostic marker in OL and as prognostic marker in OSCC.

Evaluation of CD24 and CD44 as cancer stem cell markers in squamous cell carcinoma and epithelial dysplasia of the oral cavity by q- RT-PCR

Squamous cell carcinoma (SCC) is the most common cancer of the oral cavity and may be preceded by dysplastic epithelial lesion. Oral SCC (OSCC) contains a rare subset of cancer cells with self-renewal ability, termed as cancer stem cells (CSCs). CD24 and CD44 as CSC markers are cell surface glycoproteins. These markers contribute to the onset, maintenance, and extension of tumor growth, as well as angiogenesis. In the present study, these two markers were simultaneously evaluated to provide a specific phenotype for carcinogenesis process in oral cavity. In this analytical-cross-sectional study, the expression of CD24 and CD44 genes was evaluated in 45 OSCCs (20 low-grade and 25 high-grade) and 15 oral epithelial dysplasia specimens by real-time quantitative reverse transcription polymerase chain reaction. Kruskal-Wallis and Mann-Whitney U-test, Kendall, and Spearman tests were used for statistical analysis. The significance level was considered <0.05. High expression of both markers genes was reported in two-thirds of samples. There was no significant difference between studied groups in gene expression of CD24 and CD44 whereas statistically significant association between CD24 and CD44 was observed in all three groups. This correlation was more significant in OSCC groups (P < 0.001). High expression of CSC markers in OSCC and oral epithelial dysplasia revealed the importance of accurate examination of dysplastic lesions with high expression of these markers and the possibility of malignant transformation. Regarding a significant association of two markers, further studies are necessary to provide a specific phenotype (CD44 high CD24 high) for these lesions.

Mucin-4: A novel marker for oral cancer.

Background:Mucins are high-molecular-weight glycoproteins and are implicated in diverse biological functions. MUC4, a member of transmembrane mucin family, is expressed in airway epithelial cells and body fluids such as the saliva, tear film, ear fluid and breast milk. In addition to its normal expression, an aberrant expression of MUC4 has been reported in a variety of carcinomas. Till date, very few studies have discussed about MUC4 expression in normal and cancerous oral mucosa.Aim:The aim of the study is to evaluate the expression of MUC4 in varying grades of oral squamous cell carcinoma (OSCC) and also to analyze its role played in oral carcinogenesis.Materials and Methods:Formalin-fixed paraffin-embedded tissues of five cases of normal tissue, ten cases of well-differentiated OSCC, ten cases of moderately differentiated OSCC and ten cases of poorly differentiated OSCC were retrieved from the archives of the department, and MUC4 antigen was immunohistochemically localized.Statistical Analysis:The result was subjected to statistical analysis using Pearson's Chi-square test and one-way analysis of variance.Results:About 70% of OSCC were stained positive with MUC4 antigen. Maximum intensity of staining was noted in well-differentiated OSCC. A steady decrease in MUC4 staining was noted with the increase in histological grading of OSCC.Conclusion:The findings of the study suggest that MUC4 plays a vital role in the pathogenesis of OSCC and can be regarded as a novel marker for OSCC.

Correlation between ki-67 labeling index and mitotic index in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent type of oral cancer. Counting of mitotic figures as well as the detection of Ki-67 expression by immunohistochemistry have been used to detect cell proliferation in malignant tumors. We correlated Ki-67 expression with mitotic activity and observed any notable relationship between them, to ascertain the role of Ki-67 protein as a tumor proliferative marker in OSCC. Subjects and Methods: A cross-sectional study was undertaken at a tertiary care hospital in Western Maharashtra over a period of 2 years. Fifty paraffin blocks of patients diagnosed as OSCC were included in our study, who were classified into well-differentiated squamous cell carcinoma (n = 24), moderately-differentiated squamous cell carcinoma (n = 23), and poorly differentiated squamous cell carcinoma (n = 3). Two slides per case were stained with H and E and Ki-67 marker, then observed under light microscopy to obtain Mitotic Index (MI) and Ki-67 Labeling Index (LI), respectively. Results were analyzed using mean, standard deviation, Chi-square test, and unpaired t-test. Results: Hyperplastic epithelium revealed higher Ki-67 LI as compared to normal epithelium. There was a statistically significant (P = 0.045) increase in Ki-67 LI in the proliferating margin with grade of OSCC. Positive linear correlation was noted between Ki-67 and MI in tumor proper (r = 0.186) and proliferating margin (r = 0.337) and was statistically significant in the latter (P = 0.017). Conclusions: Ki-67 LI can reliably detect the proliferative potential of cells at the invasive margin of a tumor. MI, on the other hand, can detect the cell proliferation rate of the tumor that is in correlation with the histopathological grade of OSCC.

EXPRESSION OF METASTASIS ASSOCIATED PROTEIN 1 AS A POSSIBLE PROGNOSTIC INDICATOR IN ORAL SQUAMOUS CELL CARCINOMA

INTRODUCTION: Lymph node (LN) metastasis is one of the most important prognostic factors related to survival of oral squamous cell carcinoma (OSCC). Although, metastasis associated protein 1 (MTA1) overexpression is closely correlated with the metastasis of several human cancers, its role in determining lymph node metastases in OSCC patients remains undefined. Proliferating Cell Nuclear Antigen (PCNA) is the most representative proliferating marker; yet there is a controversy as to whether it can be used as a prognostic marker in OSCC. OBJECTIVES: To evaluate the immunoexpression of MTA1 and PCNA in metastatic versus non-metastatic OSCC; and correlate it with LN metastasis. MATERIALS AND METHODS: MTA1 and PCNA immunoexpression was detected immunohistochemically in 20 OSCC specimens; 10 of which had metastatic LNs and 10 with non-metastatic LNs (used as a control group). Their correlation with LN metastasis was evaluated. RESULTS: MTA1 immunoexpression showed significant correlation with LN metastasis but not with the histologic grade of the tumor. Whereas, PCNA immunoexpression revealed a significant correlation with the histologic grade of the tumor, but not with nodal metastasis. CONCLUSIONS: The present study suggests that MTA1 protein may have a clinical potential to be used as a prognostic factor to identify pathologically node-negative OSCC patients who may be at high risk to develop regional metastasis. On the other hand, PCNA is unlikely to play an important role in predicting LN metastasis in OSCC patients. KEYWORDS: OSCC, MTA1, PCNA, LN metastasis.

Clinical Significance and Prognostic Value of the Expression of LAMP3 in Oral Squamous Cell Carcinoma.

Recent studies demonstrated high expression of lysosome-associated membrane protein 3 (LAMP3) in a variety of malignancies including esophageal squamous cell carcinoma, gastrointestinal cancer, breast cancer, and cervical cancer and its involvement in several biological activities of tumor cells. However, the expression of LAMP3 and its value in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we examined the expression of LAMP3 in OSCC tissue samples and investigated the relationship between LAMP3 and clinical characteristics of patients with OSCC. We examined mRNA and protein levels of LAMP3 in OSCC tissues and neighboring normal tissues using quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. Both the mRNA and protein levels of LAMP3 were significantly higher in OSCC tissues than in adjacent normal tissues. Chi-square analysis showed that the high LAMP3 expression was notably linked to the degree of tumor differentiation and advanced TNM stage. Univariate and multivariate analyses showed that the high LAMP3 expression was an independent prognostic marker in OSCC. Our results suggest that LAMP3 might act as a potential anticancer target and a prognostic marker in patients with OSCC.

Combined Expression of c-jun, c-fos, and p53 Improves Estimation of Prognosis in Oral Squamous Cell Carcinoma

ABSTRACTTo identify the prognostic value of c-jun, c-fos, and p53 in oral cancer, we examined the impact of immunohistochemical expression of these markers on tumor progression in 157 oral squamous cell carcinoma (OSCC). We found that c-jun or c-fos was significantly associated with lymph node metastasis, and coexpression of c-jun/c-fos, or c-jun/c-fos/p53 were significantly associated with lymph node metastasis, poor differentiation and clinical stage. The coexpression of c-jun/c-fos/p53 was identified as independent prognostic factors for overall survival. Simultaneous coexpression of these markers in OSCCs might prove to be a useful indicator for differentiation of low and high-risk patients.

Abstract 3358: Expression of ALDH1, Bmi-1 and CD24 in human oral squamous cell carcinoma and its relationship with clinical factors

Abstract [Background] A cancer stem cell (cancer initiating cell, CSC) is considered capable of self -replication, self-differentiation, drug resistance, and immune evasion. Recently, CSC has become increasingly important in the treatment of malignant tumors. Cancer stem cells express specific molecules termed CSC marker, including aldehyde dehydrogenase (ALDH) 1, B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and CD24, and their expression has been reported to be the potential prognostic values. However, the prognostic values of ALDH1, Bmi1, and CD24 expression in patients with oral cancer are less understood. [Purpose] The aims of present study were to evaluate the expression of ALDH1, Bmi1, and CD24 in oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the CSC marker expression, clinical stages, histological differentiation, the classification of invasion mode, cerebral lymph node metastasis and disease-free survival rate. [Materials and Methods] Tissue specimens were obtains from 103 patients with OSCC after surgery or biopsy. Immunohistochemistry was used to assess ALDH1, Bmi1, and CD24 protein using at least 10% staining-positive cells as the definition of positive staining. [Results] Immunohistochemical analysis of 103 cases showed that 31 cases (30%) expressed ALDH1. There was no relationship between ALDH1 expression and clinical stages or metastasis. However, there was significant association between ALDH1 expression and histological differentiation, or classification of invasion mode or disease-free survival rate. Otherwise, 39 cases (38%) cases of 103 OSCC patients expressed Bmi-1. There was significant association between Bmi-1 expression and invasion mode or disease-free survival rate. Sixty four cases (62%) expressed CD24. There was significant association between CD24 expression and histological differentiation. [Conclusions] These findings suggested that the expression of ALDH1 and Bmi-1 as CSC markers in OSCC may be good marker indicating survival in patients with OSCC. Citation Format: Tetsuya Tamatani, Natsumi Takamaru, Kenji Fujisawa, Hirokazu Nagai, Youji Miyamoto. Expression of ALDH1, Bmi-1 and CD24 in human oral squamous cell carcinoma and its relationship with clinical factors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3358.

Prevalence of human papillomavirus in oral squamous cell carcinomas in northern Spain.

The aim of this study was to analyze the prevalence of high-risk HPV in oral squamous cell carcinoma (OSCC) in a northern Spanish population, as well as to ascertain the prognostic role of p16INK4a expression. The examination samples were collected from paraffin tissue blocks, from 125 patients surgically treated between 1996 and 2007. All cases were histologically evaluated, and the presence of HPV was assessed by p16 and p53immunohistochemistry followed by DNA detection by in situ hybridization (ISH) and polymerase chain reaction (PCR) amplification using the combination of consensus primers MY11/GP6+. Fourteen cases (11%) were p16-immunopositive, and p53 was scored positive in 73 cases (58%). Five cases (4%) showed a simultaneous p16-positive and p53-negative immunostaining. ISH was negative in all the cases. Among the p16INK4a-immunopositive cases, PCR amplification failed to reveal HPV DNA in any tumor samples. There were no statistically significant differences in any clinical or pathological characteristics of the patients regarding p16INK4a expression. T classification, neck-node metastasis, and clinical stage showed outcome relevance. However, no significant differences in cause-specific survival based on p16INK4a were observed. We did not find any high-risk HPV types in our patients, thus, are unlikely that HPV has an important role in the etiology of OSCC. p16INK4a protein was neither an accurate marker of HPV infection nor a prognosis marker in OSCC.

Association of P53 Protein Overexpression with Clinicopathological Features of Oral Squamous Cell Carcinoma Patients in Bali

Background: Oral cancer was a major health problem with a high incidence rate worldwide. Oral Squamous Cell Carcinoma (OSCC) in Bali, ranked as the second most common cancer after cervix carcinoma. Our understanding of OSCC hasn’t yielded a satisfactory clinical outcome; therefore, further studies about the role of biomolecular markers in OSCC are still needed. One of the biomolecular markers for prognosis and predictor for OSCC that has been a topic of research to date is p53. Method: This is a cross-sectional analytical study of 36 samples to determine the correlation between p53 overexpression with age group, tumor location, tumor stage, and tumor grade in OSCC patients. Data was processed descriptive and analytical using Chi-Square/Fisher 's Exact Test methods with a significance value of p <0.05 was considered significant. Results: From the 36 samples collected, the mean age was 55,19±14,712 years, 19 samples (52.8%) were women, 21 samples (58,3%) were ?60 years, 24 samples (66,7%) had OSCC on the postero inferior region, 19 samples (52,8%) were in high stage group, 22 samples (61,1%) had high grade OSCC, and 22 samples (61,1%) showed high p53 overexpression. There were significant differences in proportion between OSCC grade with p53 expression (Chi-square test p=0,013; r=0,416; OR=6,12 CI=95%) and between OSCC N stage with p53 expression (Fisher's Exact Test p=0,024; r=0,396; OR=6,33 CI=95%). Conclusion: There were significant differences in the proportion between OSCC grade and N stage with p53 expression. Therefore, p53 overexpression can be used as a prognostic indicator and predictor of lymph node involvement in OSCC.

Correlation of Cyfra 21-1 levels in saliva and serum with CK19 mRNA expression in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for 90% of malignant lesions of oral cavity. The study assessed the potential of Cyfra 21-1 as a tumor marker in OSCC. The study included 50 patients of OSCC to evaluate levels of Cyfra 21-1 in serum and saliva by electrochemiluminescent immunoassay (ECLIA) and CK19 messenger RNA (mRNA) expression in tissue by florescent quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) along with healthy individuals as control. The salivary and serum Cyfra 21-1 levels in patients of OSCC were significantly higher compared to controls (p value < 0.01). There was a 2.75-fold increase in CK19 mRNA expression in OSCC cases compared to controls. A significant positive correlation was found between serum and salivary Cyfra 21-1, serum Cyfra 21-1, and CK19 mRNA expression and between salivary Cyfra 21-1 and CK19 mRNA expression. Among these, correlation between serum and salivary Cyfra 21-1 was highly significant. Salivary and serum Cyfra 21-1 showed significantly elevated levels in grade II OSCC compared to grade I histopathologically. Elevated levels of salivary Cyfra 21-1 were associated with recurrence in OSCC patients. Reverse operating curve constructed using 3ng/ml as a cutoff for serum Cyfra 21-1 revealed the sensitivity and specificity to be 88 and 78.2%, respectively. Using a cutoff value of 8.5ng/ml for salivary Cyfra 21-1, the sensitivity was found to be 93.8% and specificity 84.3%. We advocate salivary Cyfra 21-1 as a better diagnostic marker over serum Cyfra 21-1 as well as a potential marker in the prognosis of OSCC.

Evaluation of Serum Beta-2 Microglobulin as a Diagnostic and Prognostic Marker in Oral Squamous Cell Carcinoma and Leukoplakia

Background: The disfiguring defects, functional loss and thus the mortality rate in oral squamous cell carcinoma (OSCC) can be significantly reduced by its early diagnosis. Tumour markers are being studied which could aid in screening, diagnosis, study prognosis and monitor the response to treatment. This research was conducted to study the role of Beta - 2 microglobulin (B2M), a tumour marker in OSCC and leukoplakia. Method: Serum from 30 cases of OSCC and leukoplakia each and 20 controls was studied Materials and methods: IMMULITE/ IMMULITE 1000 kit was used to assess the B2M levels. Findings: B2M levels in various stages and were higher degree of differentiation of OSCC (p<0.001) and as the stages (p<0.05) and grades of dysplasia (p<0.001) increased in leukoplakia. Conclusion: Serum B2M levels were higher in OSCC and leukoplakia than controls. So B2M can be considered as a diagnostic and prognostic marker.