Apoptosis-associated markers and clinical outcome in human oral squamous cell carcinomas

Background:  Apoptosis is a genetically regulated cell death involved in the deletion of cells in normal or malignant tissues. Proteins of the Bcl-2 family play a key role in the control of apoptosis and carry out both pro-apoptotic and anti-apoptotic functions. The present study evaluated the prognostic value of Bcl-2 and Bax expression at the invasive front of oral squamous cell carcinoma (OSCC), taking clinicopathological findings into account.
Methods:  Fifty-six specimens of OSCC were randomly selected, and Bcl-2 and Bax expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded pre-treated specimens at the invasive front of OSCC. Clinicopathological data were gathered and patient survival was analysed.
Results:  No significant relationship was found between Bcl-2 or Bax expression and clinical variables. Patients with Bcl-2 expression had a worse prognosis than those without Bcl-2 expression, but the difference did not reach statistical significance. Patients with Bax expression had a significantly better prognosis than those without Bax expression ( P  <   0.05). In univariate analyses, T category, mode of cancer invasion and Bax expression showed significant correlations. Multivariate analysis revealed that the mode of cancer invasion and Bax expression were significant and independent variables. Bax expression was found to be the strongest independent prognostic parameter. Patients with negative Bcl-2 expression and positive Bax expression had a significantly better prognosis ( P  <   0.005).
Conclusion:  We suggest that Bax expression at the invasive front of OSCC is a significant predictor of prognosis and that it is therefore important to investigate the expression of Bcl-2 and Bax in this disease.     

Estimation of serum leptin in oral squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 69–73
Background:  Cachexia contributes significantly to mortality in cancer patients; role of cytokines in inducing cachexia is an emerging view. Leptin, a homologous protein of cytokine family, is found to be decreased in serum with cachexia. The purpose of this study was to compare serum leptin levels of oral squamous cell carcinoma patients with that of control group and correlate it with body mass index.
Method:  Serum samples of 31 oral squamous cell carcinoma patients and that of 28 healthy individuals were subjected to evaluation of serum leptin levels (ng/ml) using enzyme-linked immunosorbent assay.
Results:  A significant reduction in leptin level of oral squamous cell carcinoma patients was observed. Definite correlation between body mass index and serum leptin and also between serum leptin levels of various histopathological variants of oral squamous cell carcinoma was observed.
Conclusion:  The results of this study suggest that evaluation of serum leptin level can provide status of cachexia in oral squamous cell carcinoma patients.     

Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongue

J Oral Pathol Med (2010) 39 : 667–671 Background: Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow‐up and status in primary SCCs of the mobile tongue. Methods: Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow‐up and status in patients treated initially by surgery. Results: Tumor shape was significantly associated with the presence of perineural invasion. Well‐defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill‐defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well‐defined shaped tumors. Conclusion: Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue.     

血清SCC-Ag的变化对口腔鳞状细胞癌患者预后的影响

目的 研究血清鳞状细胞癌抗原(SCC-Ag)水平的变化对口腔鳞癌患者预后的影响。方法 采用ELISA检测了58例口腔鳞状细胞癌（鳞癌）患者手术前后血清SCC-Ag水平的改变。结果 术前及术后血清SCC-Ag值<1.5 μg/L的口腔鳞癌患者术后发生复发或转移发生率为15.6%和3.1%;术前和术后血清SCC-Ag水平>1.5 μg/L的口腔鳞癌患者术后发生复发或转移发生率为83.3%和95.5%;术前血清SCC-Ag水平>1.5 μg/L的口腔鳞癌患者术后血清SCC-Ag水平下降且SCC-Ag值<1.5 μg/L,其术后复发或转移发生率为25%。结论 血清SCC-Ag可能与口腔鳞癌的发生发展有关,其结果可作为判断患者病情的进展及肿瘤是否复发或转移。     

Alteration of integrin expression in oral squamous cell carcinomas

OBJECTIVE: This study examines the intensity of expression of beta 1, alpha 2, alpha 3, alpha 5, alpha 6 integrin subunits in oral squamous cell carcinoma (SCC) as opposed to normal oral epithelium, and the intensity of expression and distribution pattern of the above subunits in relation to tumour differentiation grade. MATERIALS AND METHODS: Cryostat sections of 25 cases of oral SCC and 15 cases of normal oral epithelium were studied by immunohistochemistry (APAAP method). RESULTS: The intensity of expression of beta 1, alpha 2 (Pearson chi 2 P < 0.001) and alpha 6 (Test for Trend P < 0.05) integrin subunits was reduced significantly in SCC compared to normal oral epithelium. All integrin subunits were mainly expressed in the peripheral cell layer of tumour islands. No correlation was found between the intensity of integrin expression and the degree of differentiation in SCC. The same applied to the distribution pattern of the integrin subunits. By means of cross examination of all integrins, the loss of intensity of alpha 2 beta 1 integrin expression was found to have the strongest correlation with oral SCC (Ordered Logistic Regression). CONCLUSIONS: Reduced intensity of expression of all subunits was found in oral SCC compared to normal epithelium. Further investigation is needed to determine whether alpha 2 beta 1 integrin expression can be used as a prognostic evaluator for the behaviour of the disease.     

Prognostic impact of p53 and p63 immunoexpression in oral squamous cell carcinoma

BACKGROUND: The role of p53 and p63 proteins in the prognosis of oral squamous cell carcinoma (OSCC) is still debatable. Our aim here was to investigate the relationship between the immunoexpression of these proteins with some clinicopathologic parameters of prognostic significance in OSCC. METHODS: Formalin-fixed paraffin-embedded sections from 106 patients were used for study together with the following data: primary site, histologic differentiation, recurrences, metastasis, disease-free survival and overall survival (OS). RESULTS: In OSCCs, the positive rate for p63 protein immunoexpression (87.8%) was higher than p53 (52.8%). p53 expression correlated with metastasis. Tumors negative for p53 and with strong intensity for p63 expression had a significantly higher OS. CONCLUSIONS: p53 overexpression is associated with a larger number of metastases and is correlated with a poor outcome as well as decreased intensity in p63 immunoexpression.     

UHRF1在口腔黏膜鳞癌中的表达及其对临床预后的价值研究

目的 分析泛素样含PHD和环指域1(ubiquitin like with PHD and ring finger domains 1,UHRF1)在口腔黏膜鳞状细胞癌中的表达及其临床意义。方法 收集2008—2016年间,于中国科学技术大学附属第一医院口腔颌面外科接受手术治疗的原发性口腔鳞癌患者,利用免疫荧光染色评估患者的肿瘤组织、癌旁正常组织及侵袭前沿中的UHRF1表达,了解其表达差异性。以免疫反应强度分布指数(immunoreactivity intensity distribution index, IRIDI)值4分为界限,将患者分为UHRF1高表达组和低表达组,分析UHRF1表达水平与患者临床病理特征之间的关系,利用Kaplan-Meier法对肿瘤组织中UHRF1表达水平与患者生存率的相关性进行分析,运用Cox风险模型对影响口腔癌患者生存率的相关危险因素进行分析。结果 与肿瘤侵袭前沿、癌旁正常组织相比,UHRF1在口腔鳞癌肿瘤组织中高表达(P<0.01)。口腔鳞癌组织中UHRF1的表达水平与患者性别、肿瘤大小、浸润深度相关(P<0.05)。UHRF1低表达组和高...     

维吾尔族口腔鳞状细胞癌患者中血清鳞状细胞癌抗原的表达研究

目的 探讨维吾尔族口腔鳞状细胞癌(OSCC)患者血清中鳞状细胞癌抗原(SCC-Ag)的表达.方法 采用化学发光法检测90例维吾尔族OSCC患者(OSCC组)和90例维吾尔族其他口腔恶性肿瘤患者(口腔非OSCC恶性肿瘤组)、101例维吾尔族口腔良性肿瘤患者(良性肿瘤组)和120例维吾尔族正常对照者(正常组)的血清SCC-Ag水平,并对其中60例OSCC和60例口腔非OSCC恶性肿瘤患者治疗前后SCC-Ag水平进行检测,分析SCC-Ag在OSCC诊断、治疗疗效中的意义.结果 OSCC组的SCC-Ag水平明显高于口腔非OSCC恶性肿瘤组(P=0.002),良性肿瘤组(P=0.001)和正常组(P=0.001).OSCC患者血清SCC-Ag阳性率为43.3％(39/90),明显高于其他3组(P=0.000 1).OSCC患者TNM晚期的术前SCC-Ag水平的表达高于早期水平(P<0.05).复发组和未复发组的术前、术后、放化疗后SCC-Ag水平相比较,差异均有统计学意义(P＜0.05).手术及放化疗前后鳞状细胞癌患者血清SCC-Ag水平变化差异有统计学意义(P＜0.0 1),然而,在口腔非OSCC恶性肿瘤组治疗疗效差异无统计学意义(P>0.05).结论 血清SCC-Ag对维吾尔族OSCC患者的早期诊断敏感性不高,但在评价治疗疗效,预测肿瘤复发方面有重要的临床意义.     

Prognostic significance of extranodal extension in oral cavity squamous cell carcinoma with occult neck metastases

A grade of extranodal extension (ENE) may advance risk stratification related to survival in patients with metastatic oral cavity squamous cell carcinoma (OCSCC). Pathological examination of 174 OCSCC patients who were primarily surgically treated with tumour resection and elective neck dissection was performed. Data of ENE presence, its extent (in millimetres), patients and tumour characteristics were statistically analysed with respect to disease-free survival (DFS) and overall survival (OS). Ninety patients (51.7%) were identified with occult nodal disease, with 41 patients (23.6%) presenting with ENE. Receiver operating characteristics (ROC) curve analysis set the threshold at 1.9 mm as an optimal ENE cut-off regarding both DFS and OS. Patients were divided by extent into minor ENE (≤1.9 mm) and major ENE (>1.9 mm) subgroups. The subgroup with minor ENE had significantly higher DFS and OS rates compared with major ENE. ENE cut-off threshold at 1.9 mm discriminates low and high-risk subgroups of patients with occult OCSCC in terms of DFS and OS.     

葡萄糖转运蛋白及其与口腔鳞状细胞癌的关系

葡萄糖转运蛋白(GLUT)是一组位于哺乳动物细胞膜上的非能量依赖性转运蛋白,是负责将葡萄糖向细胞内转运的主要载体。据报道,GLUT在多种恶性肿瘤组织中表达异常,且其表达与肿瘤的发生、发展及预后密切相关。GLUT有可能为口腔鳞状细胞癌的早期诊断及治疗提供一条新思路。本文就GLUT与口腔鳞状细胞癌的相关性研究进展作一综述。     

Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma

Advances in understanding of the molecular mechanisms underlying oral squamous cell carcinoma (OSCC) have resulted in an increasing number of biomarkers that can be used to predict the behaviour of this disease. The authors conducted a literature review of studies examining the role of immunohistochemistry-based protein biomarkers in predicting OSCC outcome. Only articles published in PubMed-indexed journals over the past 5 years were considered. 22 molecular biomarkers were identified and classified into five groups based on their biological functions: cell cycle acceleration and proliferation; tumour suppression and apoptosis; hypoxia; angiogenesis; and cell adhesion and matrix degradation. The cell cycle acceleration and proliferation biomarkers showed the most divergent prognostic findings. Studies on tumour suppression and apoptosis biomarkers were the most prevalent. There were only a few studies examining molecular biomarkers of hypoxia and angiogenesis, and studies examining cell adhesion and matrix degradation biomarkers have shown that this group has the greatest potential for assessing prognostic parameters. Amongst the several proteins analysed, the immunohistochemical expression levels of epithelial growth factor receptor (EGFR), p53, and matrix metalloproteinases (MMPs) have demonstrated the greatest potential for survival prediction in OSCC, but this review demonstrates that their prognostic relevance is debatable and requires further standardisation.