Expression of Survivin and Caspase 3 in Oral Squamous Cell Carcinoma and Peritumoral Tissue

Li, SX; Chai, Linyan; Cai, ZG; Jin, L-J; Chen, Y; Wu, HR; Sun, Zheng

doi:10.7314/apjcp.2012.13.10.5027

Cited by 23 publications

(11 citation statements)

References 23 publications

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“…Previous studies used immunohistochemical assays to detect the expression of survivin in oral mucosae, and observed that its expression in precancerous lesions that had not yet progressed towards malignancy and had progressed to complete squamous cancer were 33% (10/30) and 94% (15/16), respectively (12,13). Previous studies revealed that survivin gene expression was also present in various precancerous damaged tissues, including oral leukoplakia, colon polyps, mastitis or keratotic dermatitis (14,15). The present study obtained similar results, as the expression levels of survivin were gradually increased during the progression from abnormal cell proliferation to malignant transformation.…”

Section: Discussionsupporting

confidence: 79%

Impacts of survivin and caspase-3 on apoptosis and angiogenesis in oral cancer

Yang

Ding

et al. 2017

Oncology Letters

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Abstract. The present study aimed to investigate the impact of survivin and caspase-3 on apoptosis and angiogenesis in oral cancer. A total of 16 oral leukoplakia cases accompanied by low-moderate epithelial dysplasia, 12 cases of oral leukoplakia accompanied by severe epithelial dysplasia, 17 cases of high-moderate differentiated oral squamous cell carcinoma and 10 cases of normal oral mucosa were selected. Immunohistochemistry was used to detect the expression levels of survivin, caspase-3, and caspase inhibitor factor VIII in lesions from each group. Terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling was performed to detect the apoptotic index of oral leukoplakia and cancer tissue. Immunohistochemistry revealed increased expression levels of survivin in oral cancer tissues, as compared with the normal mucosa, whereas the expression of Caspase-3 was decreased during malignant transformation. Microvascular density (MVD) was increased from 28.49±11.87 strips/mm 2 (mean ± standard deviation, normal control group) to 91.98±40.20 strips/mm 2 (oral cancer group). Therefore, survivin may serve an important role in oral cancer, as its expression was increased in association with a downward trend in caspase-3 expression and apoptotic index, whereas MVD was significantly increased. IntroductionAn imbalance between cell proliferation and apoptosis is important during the occurrence and development of oral cancer. This dynamic balance is essential to maintaining homeostasis, which ensures the balance and stability of the human body at the cellular level. Previous studies have observed that the reduction of apoptosis also serves a key role in oral cancer incidence and development. A previous study demonstrated that pro-apoptotic factors, including tumor protein 53 and Fas, as well as anti-apoptotic factors, including the B-cell lymphoma-2 family and inhibitors of apoptosis protein family (IAPs), serve crucial roles in the pathogenesis of oral cancer (1). Of the IAPs, survivin is the protein with the highest apoptosis inhibitory ability, and also regulates the cell cycle (2). Previous studies compared the expression profile of survivin in normal oral mucosa, oral precancerous lesions and oral cancer tissue, revealing that survivin was not expressed in the normal oral mucosa but was expressed in the early and precancerous stages of oral cancer (3-5). The positive expression rate of survivin in epithelial paraplastic tissues was ~97 and ~98% in oral cancer tissue (3-5), and its expression in distinct splice variants was also altered during tumorigenesis (6). This indicates that survivin not only serves an important role in the occurrence of oral cancer, but that the increase in its expression levels are an early event in the development of this type of cancer. A previous study also observed that survivin was associated with angiogenesis, as it was not able not be detected in quiescent endothelial cells, but was strongly expressed in angiogenic factor-stimulated endothelial cells (7). In a...

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Section: Discussionsupporting

confidence: 79%

Impacts of survivin and caspase-3 on apoptosis and angiogenesis in oral cancer

Yang

Ding

et al. 2017

Oncology Letters

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“…Increased survivin expression is commonly associated with reduced levels of apoptosis and survival rate, increased proliferative index, recurrence rate, and resistance to chemotherapy and radiotherapy, thereby identifying it as a significant independent prognostic indicator of the poor outcome in patients with most tumor types. The immunopositivity for survivin was completely negative in normal oral epithelium, as observed in other studies by Gayathri et al, 10 Lin et al, 11 Khan et al, 12 Li et al, 13 and Jinbu et al 14 Survivin is generally expressed at high levels in embryonic tissues, but present at lower or non-detectable levels in normal adult tissues due to the presence of differentiated cells. 11 In contrast to our findings, few studies have reported mild nuclear and cytoplasmic expression among sporadic cells of basal and parabasal layers.…”

Section: Discussionsupporting

confidence: 78%

Prognostic Implication of Survivin Expression in Oral Squamous Cell Carcinoma—An Immunohistochemical Study

Ajithkumar¹,

Murali²,

Vani³

2019

The Journal of Contemporary Dental Practice

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Aim: Immunohistochemical expression of survivin was analyzed among the three histological grades (well differentiated, moderately differentiated, and poorly differentiated) of oral squamous cell carcinoma (OSCC). Materials and methods:The study material consisted of 60 formalin-fixed paraffin-embedded tissue samples: 15 cases each of well, moderate, and poorly differentiated OSCC and normal oral mucosal (NOM) tissues as the control. Survivin expression was evaluated immunohistochemically and statistical analysis of data was performed using Fisher's Chi-square and analysis of variance (ANOVA) tests. Results: Survivin was expressed in all grades of OSCC, but absent in normal oral tissue samples. Poorly differentiated OSCC exhibited 51 to 75% immunopositivity (53.3%) and severe staining intensity (46.7%) for survivin, predominantly in nuclear areas. While moderately differentiated OSCC had 26 to 50% immunopositivity (40%) and moderate staining intensity (80%), 5 to 25% immunopositivity (40%) with moderate staining intensity (86.7%) was observed in well-differentiated OSCC. Overall, there was a statistically significant difference among the three grades of OSCC in relation to survivin immunopositivity and immunoreactivity (p < 0.01). Conclusion:This study supports the use of survivin as a potent diagnostic and prognostic marker for OSCC. Clinical significance: Increased survivin expression and its nuclear localization appeared to correlate with a higher grade of malignancy suggesting unfavorable prognosis.

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“…Hence, it blocks the apoptosis mediated by caspase-3 and finally leads to the development of OSCC. [ 16 ] In an analysis of caspase-3 level estimation in gastric cancer, the results showed the total absence of caspase-3 activity in gastric cancer and in the peritumoral area. On the other hand, the normal mucosa divulged the caspase-3 activity, and it was suggested that lack of caspase-3 activation is involved in the transformation to gastric carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma

Veeravarmal

Austin

Siddavaram

et al. 2016

J Oral Maxillofac Pathol

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Context:The epithelium atrophy, as the oral submucous fibrosis (OSMF) progresses, is believed to be an after effect of stromal fibrosis, hyalinization, decrease in vascularity and cellularity and is considered as “ischemic atrophy.” Due to hypoxia, caspase-3 get activation and subsequent decrease in viable cell count can occur.Aims and Objectives:To determine caspase-3 expression in various grades of OSMF and oral squamous cell carcinoma (OSCC) to find out whether upregulation of apoptosis is responsible for the epithelial changes in OSMF.Subjects and Methods:The control tissue (15 samples from normal oral mucosa) and study group comprising 97 cases of OSMF of different grades and OSCC associated with OSMF were stained with caspase-3 antibody, and the percentage of positive cells was calculated using ImageJ software.Statistical Analysis:The results obtained were statistically analyzed using ANOVA and Tukey's honest significance difference test and Mann–Whitney U-test.Results:There was a nuclear expression of caspase-3 in basal and parabasal layers of normal epithelium. There was cytoplasmic expression of caspase-3 in OSMF without dysplasia, total absence of caspase-3 expression in dysplastic epithelium and in majority cases of OSCC. The caspase-3 percentage was increased in OSMF (0%–53%) when compared with OSCC (0%–8%). The statistical comparison of caspase-3 among normal, OSMF and OSCC patients revealed significant correlation (P < 0.00010). The comparison within different grades of OSMF and between dysplastic and nondysplastic epithelium OSMF also showed significance (P < 0.019).Conclusions:The decreased expression of caspase-3 in disease progression reflects its role in the malignant transformation.

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Expression of Survivin and Caspase 3 in Oral Squamous Cell Carcinoma and Peritumoral Tissue

Cited by 23 publications

References 23 publications

Impacts of survivin and caspase-3 on apoptosis and angiogenesis in oral cancer

Impacts of survivin and caspase-3 on apoptosis and angiogenesis in oral cancer

Prognostic Implication of Survivin Expression in Oral Squamous Cell Carcinoma—An Immunohistochemical Study

Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma

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