Non-metastatic Oral Squamous Cell Carcinoma Research Articles

Expression of HIF-1α and Nestin in oral squamous cell carcinoma and its association with vasculogenic mimicry.

To evaluate and correlate the expression of HIF1-α and Nestin in tumor center and periphery of nonmetastatic, and recurrent oral squamous cell carcinoma (OSCC) and its association with vasculogenic mimicry. About 60 histopathological proven cases of OSCC with proper tumor center and periphery were collected. Among them 25 are nonmetastatic, 25 metastatic, and 10 recurrent cases of OSCC. Immunohistochemical analysis of HIF, Nestin, and CD31/PAS (periodic acid Schiff) was done. Based on the extent of tumor cells stained, staining intensity and index score, expression of both HIF and Nestin was highly significant in periphery of metastatic OSCC with a P value of 0.003* and 0.001*. The total number of vessels expressed in nonmetastatic, metastatic, and recurrent OSCC was not significant but the overall expression of CD31/PAS was significant in the periphery of the tumor with a P value of 0.024*. Correlating the overall expression, HIF showed a positive relation with Nestin and CD31/PAS with a P value of 0.026* and 0.038* in nonmetastatic OSCC using Pearson's correlation coefficient analysis. Based on the above results hypoxia plays a vital role in cancer stem cells maintenance with the formation of vessel-like structures by tumor cells at an early stage of cancer development.

Comparative Assessment of E-cadherin’s Expression between the Metastatic and Non-metastatic Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Comparative Assessment of E-cadherin’s Expression between the Metastatic and Non-metastatic Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Inverse correlation of CD3 & vascular endothelial growth factor in incisional oral squamous cell carcinoma biopsies predicts nodal metastasis & poor survival of patients.

Oral squamous cell carcinoma (OSCC) is widely prevalent in the Indian subcontinent mainly due to habit-associated aetiologies. Immune regulation and angiogenesis are the part of tumourigenesis that play a crucial role in metastasis and survival. However, the concurrent expression of vascular endothelial growth factor (VEGF) and CD3 (immune regulator receptor on T-lymphocyte) in the same OSCC tissue samples has not been reported in the Indian population. The present study evaluated the expression of CD3+ T-cells and VEGF in OSCC tissue samples and studied the clinicopathological correlation and survival analysis in an Indian population. This was a retrospective study conducted on 30 formalin-fixed and paraffin embedded sections which were histologically diagnosed as OSCC cases comprising of 15 metastatic OSCC and 15 non-metastatic OSCC with available clinical data and survival status. Reduced expression of CD3+ T-cells and increased VEGF expression were observed in metastatic OSCC samples. The correlation of expression of CD3+ T-cells and VEGF with clinicopathological parameters showed a significant association between these markers with age, nodal status, site of the lesion and survival. Reduced expression of CD3+ T-cells in OSCC was found to be associated with a significantly poor survival. VEGF was found to be over expressed in metastatic OSCC as compared to that in non-metastatic OSCC. The study findings suggest that the evaluation of CD3 and VEGF in incisional OSCC biopsies can be considered for predicting the survival outcome and metastasis.

Preliminary Extracellular Vesicle Profiling in Drainage Fluid After Neck Dissection in OSCC

Lymph node metastasis is related to poor prognosis in oral squamous cell carcinoma (OSCC), and few studies have explored the relevance of postoperative drainage fluid (PDF) in metastasis. Extracellular vesicles (EVs) are nanosized vesicles that can transfer oncogenic molecules to regulate tumorigenesis. However, the proteomic profile of postoperative drainage fluid–derived EVs (PDF-EVs) in OSCC has not been elucidated. Herein, we collected drainage fluid from OSCC patients after neck dissection to investigate the difference in PDF-EVs between patients with metastatic lymph nodes (the LN+ group) and nonmetastatic lymph nodes (the LN− group). The proteomic profile of PDF-EVs from the LN+ and LN− groups was compared using label-free liquid chromatography tandem-mass spectrometry–based protein quantification. The results revealed that PDF-EVs were mainly derived from epithelial cells and immune cells. A total of 2,134 proteins in the PDF-EVs were identified, and 313 were differentially expressed between the LN+ and LN− groups. Metabolic proteins, such as EHD2 and CAVIN1, were expressed at higher levels in the LN+ group than in the LN− group, and the levels of EHD2 and CAVIN1 in the postoperative drainage fluid were positively correlated with lymph node metastasis. Our study revealed previously undocumented postoperative drainage fluid–associated proteins in patients with metastatic OSCC, providing a starting point for understanding their role in metastatic and nonmetastatic OSCC.

Long Noncoding RNA LEMD1-AS1 Increases LEMD1 Expression and Activates PI3K-AKT Pathway to Promote Metastasis in Oral Squamous Cell Carcinoma.

Background The survival rate of oral squamous cell carcinoma (OSCC) is only 50% due to a high incidence of metastasis. Long noncoding RNAs (lncRNAs) play a crucial role in OSCC genesis and progression, although their potential role in the metastasis of OSCC remains unclear. Methods The transcriptome of 5 metastatic and 5 nonmetastatic OSCC samples were assessed by RNA sequencing. The biological functions and regulatory mechanisms of LEMD1-AS1 in OSCC were explored by in vitro and in vivo assays. Results We identified 487 differentially expressed mRNAs (DEmRNAs) and 1507 differentially expressed lncRNAs (DElncRNAs) in OSCC with cervical lymph node (LN) metastasis relative to the nonmetastatic samples. In addition, both LEMD1-AS1 and its cognate LEMD1 were up-regulated in metastatic OSCC compared to nonmetastatic OSCC. Gain-of-function, loss-of-function, and rescue experiments indicated that LEMD1-AS1 upregulated LEMD1 to increase OSCC migration and invasion in vitro and in vivo. Mechanistically, LEMD1-AS1 stabilized LEMD1 and increased its mRNA and protein levels, and consequently activated the PI3K-AKT signaling pathway to facilitate OSCC metastasis. Conclusions We established the lncRNA-mRNA landscape of metastatic OSCC, which indicated that LEMD1-AS1 enhanced OSCC metastasis by stabilizing its antisense transcript LEMD1. Thus, LEMD1-AS1 is a potential biomarker for predicting metastasis, as well as a therapeutic target of OSCC.

Neutrophil-to-lymphocyte ratio as a prognostic factor in oral squamous cell carcinoma - A single-institutional experience from a developing country.

Background:Cell-mediated inflammatory response, neutrophils, lymphocytes and monocytes are being recognized as an important role in carcinogenesis. Neutrophil-to-lymphocyte ratio (NLR) has been used as an independent prognostic factor in varieties of cancers. NLR can be easily determined from complete blood count, and it could be considered as a simple and inexpensive prognostic marker.Aim:In this study, we evaluate the prognostic significance of NLR in patients with oral squamous cell carcinoma (OSCC).Materials and Methods:Clinical and epidemiological data of all biopsy-proven nonmetastatic OSCC treated between 2014 and 2018 were taken into consideration. Pretreatment absolute neutrophil and lymphocyte counts were used to get NLR. Using univariate and multivariate analysis, the impact of NLR on overall survival (OS) and progression-free survival (PFS) was investigated.Results:A total of 50 patients of OSCC with median pretreatment NLR ratio of 2.52 were identified. Based on the median NLR as a cutoff, patients were classified into two groups, i.e., high NLR and low NLR. Elevated NLR was significantly associated with lymph node metastasis (P = 0.01). Four-year OS and PFS were significantly better for patients with low NLR when compared with high NLR group (51.4% vs. 100%, P = 0.001). Four-year PFS for high and low NLR groups was 38.8% and 87.8% (P = 0.002). Multivariate analysis confirmed that NLR is an independent prognostic factor (P = 0.003).Conclusion:Pretreatment NLR provides a simple, cheap and early predictor of outcome in this group of patients. However, an optimal cutoff value of NLR should be determined, for which larger sample size and prospective studies are required.

QUANTITATIVE ASSESSMENT OF TUMOR ASSOCIATED TISSUE EOSINOPHILIA IN ORAL SQUAMOUS CELL CARCINOMA (CLINICOPATHOLOGICAL STUDY).

ABSTRACT INTRODUCTION: Oral Squamous cell carcinoma (OSCC) is the 11th most common cancer worldwide. Tumor stroma consists of various inflammatory cells resulting from the host-response to tumor cell. Increased tissue eosinophil levels have been reported in various malignancies including OSCC. Tissue eosinophilia is a regular finding in allergic and parasitic disorders, but their role still needs to be evaluated in OSCCs. Specific stains as Congo red is a useful diagnostic means for detecting eosinophils owing to their distinctive quality to combine with eosinophils. OBJECTIVES: was to evaluate and compare eosinophilic infiltration in both metastatic and non-metastatic oral squamous cell carcinoma using Congo red stain and their correlation to the tumor grade. MATERIAL AND METHODS: Fifty histopathologically proven OSCC were included in this study and were allocated into 2 groups where the first group included 25 cases of metastatic OSCC and the remaining 25 cases are non-metastatic OSCC. Congo red was utilized as a distinct stain for eosinophils. Each specimen slide was inspected under high power in 10 successive microscopic fields to count eosinophils. RESULTS: the eosinophilic count was found to be higher in non-metastatic tumors when compared to metastatic tumors. CONCLUSION: eosinophilic count is a strong indicator of the stage of the tumor and its differentiation. KEY WORDS: Carcinoma, Congo Red, Eosinophils, Eosinophilia, Mouth Neoplasms, Squamous Cell.

Survivin Expression in Metastatic and Nonmetastatic Oral Squamous Cell Carcinoma: A Comparative Study

Aim: Survivin is a multifunctional protein chiefly involved in apoptosis and cell cycle regulation. Increased expression of survivin in tumors and fetal tissue determines its antiapoptotic activity. The aim of the study is to identify the immunoexpression of survivin in metastatic and nonmetastatic oral squamous cell carcinoma (OSCC) and also to evaluate and compare the expression of survivin in metastatic and nonmetastatic OSCC of buccal mucosa. Materials and Methods: In total, 40 histopathologically proven cases of OSCC, including 20 metastatic and 20 nonmetastatic cases, are selected. Among the 20 metastatic and nonmetastatic cases, 10 well-differentiated and 10 moderately differentiated squamous cell carcinoma cases were included and were subjected to immunohistochemical staining for survivin expression. The results were analyzed by SPSS version 11.5 using chi-square test. Results: The expression of survivin in metastatic and nonmetastatic tumors is 15%–70% and 15%–60%, respectively. When comparing the cases of moderately differentiated squamous cell carcinoma in metastatic and nonmetastatic tumors, 70% cases show moderate staining intensity. Conclusion: The survivin expression was comparatively high in metastatic OSCC. Also based on the aforementioned results, survivin expression was high in increasing grades of OSCC.

The role of the histones H3K9ac, H3K9me3, HP1γ, and H3K36me3 in oral squamous cell carcinoma loco-regional metastasis and relapse

Molecular markers with unequivocal significance in predicting cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) has not yet been identified. Histones are DNA-binding proteins that can regulate gene expression, and some studies have shown that such proteins are implicated with tumor development and progression. This study aimed to investigate the expression of some histone modifications in OSCC and their roles in cervical lymph node metastasis. To address this goal, H3K9ac, H3K9me3, HP1γ, and H3K36me3 expression levels were investigated immunohistochemically in a retrospective metastatic and non-metastatic OSCC samples. We analyzed the association between these markers with clinical-pathological data and survival rates. Hyperacetylation of H3K9ac was associated with cervical lymph node metastasis and local relapse. High expression levels of H3K9m3 were related to age and symptomatology. Furthermore, it was also found a statistically significant association between high HP1γ-expressing tumors and tumor size. However, no markers were associated with reduced overall survival rate. Our results suggest that covalent histone modifications contribute to OSCC behavior, and H3K9ac may play a critical role in OSCC-derived cervical lymph node metastasis.

Downregulation of MicroRNA-551b Correlates With Dissemination of Human Oral Squamous Cell Carcinoma

Altered expression of microRNAs contributes to invasion and metastasis of many human cancers; however, the importance of microRNAs in head and neck cancers remains to be elucidated. In this study, we examined whether altered microRNA (miR)-551b expression correlated with invasive phenotypes of human oral squamous cell carcinoma (OSCC) invivo and invitro. Real-time polymerase chain reaction was used to detect the expression level of miR-551b in 71 OSCC tissues with lymph node metastasis and 50 nonmetastatic OSCC tissues. We also constructed miR-551b mimic-transfected cell lines HN4 and HN12. The effects of overexpressing miR-551b on the proliferation, migration, and invasion of OSCC cells were examined using Cell Counting Kit 8 (Dojindo, Kumamoto, Japan), plate clone formation, wound healing, and Transwell invasion experiments (Corning, Corning, NY).The association between clinical pathologic parameters and the expression level of miR-551b was analyzed using Kaplan-Meier survival analysis. The expression of miR-551b measured 0.33±0.11 in the 71 OSCC tissues with lymph node metastasis versus 0.54±0.06 in the 50 tissues with non-lymph node metastasis (P=.021).Regarding OSCC patients, the expression of miR-551b negatively correlated with patients' overall survival (P=.035). The ectopic expression of miR-551b inhibited the invasion and migration of OSCC cells. This is the first report showing that reduced miR-551b expression may be an event leading to OSCC invasion and metastasis.

Pancytokeratin immunostained tumor buds and cytoplasmic pseudofragments are reliable early predictive variables for regional lymph node metastatic risk assessment of oral squamous cell carcinoma.

The 5-year survival rate in patients with cervical lymph node metastasis is reported to be 20-36% post surgery as compared to 63-86% in patients without nodal involvement. This necessitates assessing the metastatic potential of OSCC patients. To evaluate the role of Pancytokeratin immunostained tumour buds and cytoplasmic pseudofragments with other histopathological and immunohistochemical variables in predicting metastatic risk of Oral Squamous Cell Carcinoma (OSCC). Retrospective study on archival tissues of OSCC available from the Department of Oral Pathology and Microbiology. Totally. Pearson's Chi square test and Man Whitney U test were used and analysed by Statistical Package for the Social Sciences (SPSS) software version 20.0. Metastatic OSCC showed significantly high number of tumour buds (p = 0.001), cytoplasmic pseudofragments (p = 0.008), higher tumour grade (p = 0.038), lymphovascular invasion (p = 0.008) and LVD (p = 0.013), aggressive invasive tumour front pattern (p = 0.001) compared to non-metastatic OSCC. Pancytokeratin immunostained tumour buds, cytoplasmic pseudofragments and higher LYVE-1 expression may be used as independent predictors for OSCC metastasis.

Development of clinico-histopathological predictive model for the assessment of metastatic risk of oral squamous cell carcinoma.

CONTEXT:Oral cancer metastasis is the leading cause of death globally. The decision-making on the mode of surgical treatment in clinically negative lymph nodes is challenging.AIM:The aim of this study was to develop a predictive model using clinical and histopathologic parameters that may help in the assessment of the metastatic risk of oral squamous cell carcinoma (OSCC).SETTINGS AND DESIGN:Clinical data of histopathologically confirmed primary OSCC from 2014 to 2017 were retrieved from the archives. Histopathological parameters for metastasis that were considered for evaluation in the study were tumor buds, cytoplasmic pseudofragments, tumor grade, depth of invasion, invasive tumor front (ITF) pattern, and lymphovascular invasion (LVI).METHODS:Hematoxylin and eosin and pan-cytokeratin immunostained sections of metastatic and nonmetastatic OSCC were assessed for histopathological features and correlated with clinical parameters.STATISTICAL ANALYSIS USED:SPSS software (Statistical Package for Social Sciences for Windows, Version 22.0 (2013) (IBM Corp., Armonk, NY, USA)) was used for the statistical analysis. Pearson's Chi-square test was done to assess the grades of histopathological and clinical parameters between the study groups. Univariate analysis was performed to develop a clinicopathologic predictive model.RESULTS:The clinicopathologic model signifies that OSCC with clinical Stage IV, high grades of tumor buds and cytoplasmic pseudofragments, Type V ITF pattern, positive LVI, deeply invasive tumors, and poorly differentiated grades of OSCC have a high risk of developing nodal metastasis. These parameters may be used as early predictors for metastasis of OSCC both in incisional and excisional biopsy specimens.CONCLUSIONS:The proposed predictive model is simple, cost-effective, and user-friendly for the early assessment of nodal metastatic risk in clinically negative lymph nodes.

Prediction of metastasis in oral squamous cell carcinoma through phenotypic evaluation and gene expression of E-cadherin, β-catenin, matrix metalloproteinase-2, and matrix metalloproteinase-9 biomarkers with clinical correlation.

CONTEXT:Controversies prevail regarding the true predictive role of epithelial–mesenchymal transition (EMT) biomarkers in metastasis of oral squamous cell carcinoma (OSCC). There is also limited research carried on till date wherein the protein and gene expression of EMT biomarkers have been investigated simultaneously in the Indian population.AIM:The aim of this study was to assess the gene expression and quantitative protein expression of EMT biomarkers using conventional method and MATLAB software and to determine if there is any difference in the expression between metastatic and nonmetastatic OSCCs with clinicopathologic correlation.SETTINGS AND DESIGN:Twenty metastatic and nonmetastatic OSCC tissue sections each were obtained from department archives. Gene expression and quantified protein expression of EMT markers were done and correlated with clinical parameters.SUBJECTS AND METHODS:Sections immunostained for EMT biomarkers were evaluated using semi-quantitative and quantitative (MATLAB) methods. Gene expression using semi-quantitative reverse transcriptase–polymerase chain reaction was done. These findings were correlated with clinical parameters.STATISTICAL ANALYSIS USED:Pearson's Chi-square test, Student's t-test, and univariate logistic regression analysis were performed using SPSS software.RESULTS:The low immunoexpression of E-cadherin and β-catenin and the high expression of matrix metalloproteinase (MMP)-2 and MMP-9 correlate with Stages III and IV showing high metastatic risk. Furthermore, the upregulated MMP-2 and MMP-9 gene expressions in advanced clinical stages of OSCC have high metastatic potential.CONCLUSIONS:This study is the first of its kind to employ texture and color segmentation in MATLAB to objectively assess the protein expression of EMT biomarkers. This research is instrumental in studying the protein and gene expressions of EMT markers with clinical correlation.

Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk.

Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC. Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry. More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients. More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.

Caldesmon Expression in Metastatic and Non-Metastatic Oral Squamous Cell Carcinoma—A Mediator of Epithelial Mesenchymal Transition

Introduction: For the past decades long-term survival of oral squamous cell carcinoma (OSCC) patients remain unchanged which provides a wide platform for research. Caldesmon (CaD), an actin-myosin binding protein, has a contributing role in cytoskeleton modulation and cell motility. The aim of this study is to evaluate the expression of CaD in metastatic and non-metastatic OSCC and to discuss the possible role of CaD in epithelial mesenchymal transition. Materials and Methods: Archival blocks of 25 metastatic and 25 non-metastatic OSCC patients are included where CaD expression is evaluated immunohistochemically. Results: Overall expression and staining intensity of CaD were statistically significant in different grades of metastatic and non-metastatic OSCC. In summary, high expression of CaD is observed in increasing grades of OSCC but the metastatic potential of the tumour doesn’t seem to have any relation with CaD.

Tissue eosinophilia in oral intraepithelial neoplasia as a probable indicator of invasion.

To investigate the presence of eosinophils in oral intraepithelial neoplasia (OIN) and oral squamous cell carcinoma (OSCC) lesions and its relation to invasion. Ninety-nine oral biopsies were selected and subdivided into the following: OIN-1(16 cases), OIN-2 (18 cases), OIN-3 (17 cases), microinvasive OSCC (10 cases), non-metastatic OSCC (22 cases) and metastatic OSCC (16 cases). The tissue eosinophilia was evaluated histologically in slices stained with haematoxylin and eosin. Eosinophil distribution was associated with diagnosis severity (p<.01). A significant difference was found between OIN-3 or microinvasive OSCC and non-metastatic or metastatic OSCC. Stromal invasion threshold was 7 eos/10 high power field (hpf) (96.1% specificity and 62.5% sensitivity). Eosinophils were absent in OIN-1; in OIN-2, two cases were positive. In OIN-3, five cases showed tissue eosinophilia, four of which had ≥3 eos/hpf or ≥7 eos/10 hpf. Three cases were suspected of invasion; two had a previous history of OSCC with elevated eosinophil infiltrate. In microinvasive OSCC, the four positive cases presented ≥3 eos/hpf and ≥7 eos/10 hpf. Although not significantly different, non-metastatic invasive OSCC had a higher number of cases (68.2%) with ≥22 eos/10 hpf contrasting with 50% in metastatic OSCC. Our results suggest that eosinophils can be considered an indicator of invasion in OIN, helping in cases of difficult diagnosis.

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.

AKR1C1 as a Biomarker for Differentiating the Biological Effects of Combustible from Non-Combustible Tobacco Products.

Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible ones using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than eight-fold by combustible TPPs. Quantitative real time polymerase chain reaction (qRT-PCR) results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.

Possible Role of Bcl-2 Expression in Metastatic and Non Metastatic Oral Squamous Cell Carcinoma.

Oral carcinoma is a global health problem. India accounts for one-third of world burden with high prevalence rate of 2.5 million and mortality rate of 5.5 lacs per year. Oral carcinogenesis is a multistage process that frequently involves invasion and metastasis that needs early detection and treatment to improve the overall quality of life. The ability of Oral Squamous Cell Carcinoma (OSCC) to metastasize to lymph nodes does not always show a relationship with clinical staging. A spectrum of molecular mechanisms is involved in carcinogenesis, where defect in the regulation of apoptosis is assumed to contribute to the pathogenesis and progression of cancer. Apoptosis regulatory genes include the antiapoptotic protein such as B-cell lymphoma-2 (Bcl-2) gene that might be used as a molecular marker to evaluate the biological behaviour of oral cancer. To evaluate and correlate the Bcl-2 expression in OSCC patients with lymphnode metastasis and without metastasis. The study comprised of 30 samples, 15 cases of metastatic and 15 non-metastatic primary OSCC. All the cases were stained for routine Hematoxylin and Eosin (H&E), and Bcl-2 antibody by immunohistochemistry. The H&E stained sections were evaluated for Lymphocytic Infiltrate (LI) and Pattern Of Invasion (POI). Bcl-2 stained sections were evaluated for staining intensity and distribution. The differences between the groups were statistically analysed using chi-square test. The histopathological parameters, LI and POI did not show any statistical difference between the study groups. Expression of Bcl-2 in OSCC was 33.3% among the study groups, where metastatic group showed a positive expression of 13.3% and 20% in non-metastatic OSCC that did not show statistically significance among the study groups. There was no significant difference in the expression of Bcl-2 between the study groups. Apoptosis is regulated by interaction among the Bcl-2 gene family. Hence, evaluation of Bcl-2 along with other apoptotic regulating proteins could define the role in pathogenesis and prognosis of metastatic and non-metastatic OSCC.

Plectin as a prognostic marker in non-metastatic oral squamous cell carcinoma.

BackgroundOral squamous cell carcinoma (OSCC) is associated with a poor 5-year survival rate. In general, patients diagnosed with small tumors have a fairly good prognosis, but some small tumors have an aggressive behavior leading to early death. There are at present no reliable prognostic biomarkers for oral cancers. Thus, to optimize treatment for the individual patient, there is a need for biomarkers that can predict tumor behavior.MethodIn the present study the potential prognostic value of plectin was evaluated by a tissue microarray (TMA) based immunohistochemical analysis of primary tumor tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC. The expression of plectin was compared with clinicopathological variables and 5 year survival.ResultsThe statistical analysis revealed that low expression of plectin in the tumor cells predicted a favorable outcome for patients with non-metastatic disease (p = 0.008). Furthermore, the expression of plectin was found to correlate (p = 0.01) with the expression of uPAR, which we have previously found to be a potential prognostic marker for T1N0 tumors.ConclusionsOur results indicate that low expression of plectin predicts a favorable outcome for patients with non-metastatic OSCC and the expression level of plectin may therefore be used in the treatment stratification for patients with early stage disease.