The prognostic implications of the surgical margin in oral squamous cell carcinoma

The prime objective of tumour ablation in oral squamous cell carcinoma (OSCC) is the removal, with a 'margin' of normal tissue, of the whole tumour. Definition of what constitutes margin involvement varies. This study aims to examine the factors associated with close and involved surgical margins in the management of OSCC. A cohort of 200 consecutive patients with previously untreated OSCC provided the material for the study. Various clinical, operative and pathological parameters were related to the status of the surgical margin, as well as time to recurrence, and survival. Cox regression analysis of the survival was also undertaken. Of the 200 patients 107 (53.5%) had clear margins, 84 (42%) close and 9 (4.5%) involved. Poor correlation was found between the status of the surgical margin and clinical factors, but in contrast high correlation between histological indicators of aggressive disease and close or involved surgical margins. These results imply that close surgical margins in OSCC could be regarded as an indictor of aggressive disease.     

XIAP与口腔鳞癌局部淋巴结转移关系的研究

目的 探究XIAP的表达水平与口腔鳞癌局部淋巴结转移之间的关系。初步评价其表达水平是否可以作为预测口腔癌局部淋巴结转移新的靶基因。方法 收集40例原发口腔鳞癌标本及11例术后复发标本,运用免疫组化技术检测组织标本中XIAP蛋白的表达水平,评价其表达水平与淋巴结转移等临床参数之间的相关性。结果 40例原发口腔鳞癌标本中XIAP在细胞胞浆中均有不同程度的表达,其表达水平与淋巴结转移、病理分级及复发显著相关。结论 实验结果表明,细胞胞浆中XIAP的表达水平与口腔鳞状细胞癌局部淋巴结转移及术后复发密切相关,可能是口腔鳞癌淋巴转移新的促进基因。     

经首次根治性手术治疗口腔鳞状细胞癌患者的生存相关影响因素分析

目的分析口腔鳞状细胞癌(OSCC)患者的总体生存率,以及影响生存率的临床病理因素。方法采集对首次接受根治性外科手术治疗的78例OSCC患者的临床病理及随访资料进行回顾性分析。对计数、计量资料进行描述性分析;采用Kaplan-Meier法绘制生存曲线;采用COX比例风险回归模型进行单因素和多因素分析,分析患者的生存率及预后相关影响因素。结果最终纳入生存分析的患者共计68例,中位随访时间为63(6~87)个月,5年总体存活率为55.9%,随访期间因OSCC死亡患者的中位生存时间为20.5(6~52)个月。单因素分析表明,临床分期、原发灶大小、淋巴结转移、病理分化及复发转移是影响生存时间的暴露因素(P<0.05);多因素分析表明,病理分化、复发转移是影响生存时间的独立危险因素(P<0.05)。78例OSCC患者中合并发生食道鳞状细胞癌(ESCC)者有4例(5.1%)。结论根据肿瘤的临床分期(TNM分期)、原发灶大小、淋巴结转移、病理分化及复发转移可对患者的生存预后作出一定的预测,其中病理分化及复发转移是影响生存预后的独立危险因素。有吸烟饮酒史的OSCC患者应常规进行ESCC临床筛查。     

口腔鳞状细胞癌中WWP2、PTEN和p70S6K的表达及相关性研究

目的探讨WWP2、第十号染色体缺失与张力蛋白同源的磷酸酶基因（PTEN）和p70核糖体蛋白S6激酶（p70S6K）蛋白在口腔鳞状细胞癌（OSCC）组织中的差异表达及相关性,以期为其早期防治及生物治疗提供参考。 方法应用免疫组化检测12例正常口腔黏膜、20例白斑及54例OSCC组织中WWP2、PTEN和p70S6K蛋白的表达和相关性,并分析其与OSCC组中患者临床病理参数之间的关系。实验数据采用SPSS 16.0统计软件进行Kruskal Wallis test、χ²检验和Fisher′s精确检验,WWP2、PTEN和p70S6K的表达两两进行Spearman等级相关分析。 结果WWP2、PTEN和p70S6K在正常对照组、口腔白斑组及OSCC组中的强表达率分别为33.33%、40%和68.52%;91.67%、85%和48.15%以及25%、45%和75.93%,与其他组相比,以上三种蛋白的表达差异均有统计学意义（P<0.05）。相关性分析表明WWP2与PTEN之间呈负相关（r = -0.236,P = 0.028）。PTEN与p70S6K之间呈负相关（r = -0.301,P = 0.005）。WWP2与p70S6K之间呈正相关关系（r = 0.315,P = 0.003）。OSCC组织中WWP2与OSCC的临床分期有相关性,p70S6K与OSCC的分化程度和有无淋巴结转移有相关性（P<0.05）。 结论WWP2、PTEN和p70S6K在口腔黏膜癌变过程的各阶段的组织中差异表达,提示可能在OSCC的发生、发展过程中起重要作用。     

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background:  Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine.
Methods:  This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11–17 years for OSCC (mean 13.3), 12–22 years for OLP (mean 15.9) and 12–17 years for hyperkeratosis (mean 14.5).
Results:  Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 ( n  = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53- mutated out of 31 tested. One TP53- mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site.
Conclusion:  TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.     

骨桥蛋白及其受体CD44v6在口腔鳞状细胞癌中的定量表达及意义

目的探讨骨桥蛋白（OPN）及其受体CD44v6在口腔鳞状细胞癌（OSCC）中的蛋白定量表达、临床意义及二者之间的关系。方法应用EnVisionTM法检测正常口腔黏膜（n=12）和OSCC患者（n=59）肿瘤组织中OPN和CD44v6的表达,结合图像分析系统进行定量分析,统计不同临床、病理指标下OSCC肿瘤组织中OPN的表达情况以及两种蛋白表达的相互关系。结果OPN在OSCC肿瘤组织中的表达显著高于正常口腔黏膜（P<0.05）。OPN的表达与OSCC不同临床分期、颈淋巴结转移有相关性,在OSCC高分化和中低分化者间差异无统计学意义。CD44v6在OSCC与正常口腔黏膜中差异无统计学意义,且其表达与临床病理指标关系不密切。在OSCC中,OPN与CD44v6表达无显著相关性。结论OPN在OSCC存在过度表达,其表达水平与肿瘤临床分期以及有无淋巴结转移存在一定的相关性,CD44v6与肿瘤临床病理特征无关,而且与OPN表达无相关性。     

Twist、Snail、Slug在口腔鳞状细胞癌中的表达及其与各临床病理因素的关系

目的:探讨Twist、Snail、Slug在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达水平及其与各临床病理因素之间的关系.方法:采用免疫组织化学方法检测术前未接受放化疗的有颈部淋巴结转移或无颈部淋巴结转移的60例原发OSCC患者肿瘤切除石蜡标本中Twist、Snail、...     

Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: a retrospective study of 202 cases

Although several histopathological parameters and grading systems have been described as predictive of the treatment response and outcome of oral squamous cell carcinoma (OSCC), none is universally accepted. A new scoring system, the histological risk model, was recently described to be a powerful predictive tool for recurrence and overall survival in OSCC. The aim of this study was to verify the predictive role of the histological risk model in a cohort of 202 patients at all stages of oral/mobile tongue squamous cell carcinoma (OTSCC). Demographic and clinical data were collected from the medical records and the tumours were evaluated using the histological risk model. Statistical analyses were performed using the χ² test, the Kaplan–Meier method, and the Cox regression model. The histological risk model showed no statistical correlation with demographic or clinical parameters and did not Predict the outcome of the OTSCC patients. However, multivariate regression analysis revealed a significant correlation of the clinical disease stage with the disease outcome. Despite major efforts to identify new predictive parameters and histological systems, clinical features are still the most reliable prognostic factors for patients with OTSCC.     

Combined surgery and postoperative radiotherapy for oropharyngeal squamous cell carcinoma in Korea: analysis of 110 cases

The treatment of oropharyngeal squamous cell carcinoma (OSCC) remains controversial. This study reviews the authors' experience of treating OSCC, evaluates the oncologic outcome and assesses the factors affecting local/regional recurrence. A retrospective analysis of 110 consecutive OSCC patients treated primarily by surgery and/or postoperative radiotherapy was carried out. 82% of patients had advanced disease (stage III or IV). The 5-year overall survival and disease specific survival rates (DSSR) were 58% and 65%, respectively. The DSSR of the soft palate or posterior pharyngeal wall, tonsillar area, and base of tongue were 80%, 62%, and 51%, respectively (P<0.05). The 5-year DSSR according to the American Joint Committee on Cancer stages was 94% for early stage and 56% for advanced stage (P<0.05). The overall recurrence rate was 38% (42 patients). The most frequent site of recurrence was the neck (46%). Only 14% of patients with recurrences were treated successfully. Positive resection margins and the presence of pathologic lymph nodes influenced the recurrence at the primary lesion and in the neck, respectively, in a statistically significant manner. Surgery and postoperative radiotherapy provided a superior outcome in patients with advanced OSCC. A randomized study is required to assess the oncologic and functional superiority of surgery or chemoradiation.     

Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma

Background

Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all cancers with predominant occurrence in middle aged and elderly males. Tumour recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) have been suggested to play a certain role in variety of tumours. The aim of this study was to investigate the relationship of pretreatment serum IL-6 and TNF-α levels on tumour recurrence in patients with OSCC in order to identify potential biomarkers for the early detection of disease recurrence.

Material and Methods

The patients with newly diagnosed OSCC were treated and followed from the first visit from November 2006 until January 2008. Serum IL-6 and TNF-α concentrations were measured. The records of the patients were re-examined in July 2012 and data were recorded about cancer characteristics and tumour recurrence. Disease free survival was analyzed by Kaplan-Meier survival curves, log rank test and Cox proportional hazards regression.

Results

Serum IL-6 was shown as an independent risk factor for tumour recurrence.

Conclusions

Pretreatment serum IL-6 concentration may be a useful biomarker for identification of OSCC patients with increased risk of the disease recurrence. Key words: Serum IL-6, serum TNF-α, oral cancer, recurrence.     

中期因子与口腔鳞癌血管新生及预后的关系

目的:探讨中期因子(Midkine,MK)与口腔鳞癌(oral squamous cell carcinoma,OSCC)临床病理及其预后的关系,并研究其与微血管密度(microvessel density,MVD)的相关性.方法:应用免疫组化SP法检测63例OSCC中MK的表达;用CD34标记肿瘤血管内皮细胞计数肿瘤MVD,并对所有病例进行随访.结果:MK在OSCC组织中的表达显著高于正常口腔黏膜组织(P＜0.05);MK的表达与颈淋巴结转移存在相关性(P＜0.05),而与病人的性别、年龄及病理分化程度无关(P＞0.05);MK表达阳性组的MVD高于MK表达阴性组(P＜0.05);MK的表达与MVD呈正相关(P＜0.05).生存分析显示MK阴性组的5年生存率高于MK阳性组.术后复发组和无复发组的MK表达阳性率间无明显差异(P＞0.05).结论:MK的表达是OSCC的不良预后因子,OSCC中MK的高表达与血管生成密切相关,研究MK与肿瘤血管形成的关系可为抗血管生成治疗提供理论依据.     

转录抑制因子Snail在口腔鳞状细胞癌中的表达及其与临床病理特征及预后多因素的关系

目的 研究转录抑制因子Snail在口腔鳞状细胞癌(以下简称口腔鳞癌)中的表达及其与多种临床病理因素之间的关系,探讨其在口腔鳞癌治疗及预后评估中的意义。方法 采用免疫组织化学染色半定量的方法检测83例术前未接受放、化疗或其他特殊治疗的原发性口腔鳞癌患者标本中Snail的表达情况,并对其与口腔鳞癌患者的临床病理因素、转移及预后之间的关系进行统计学分析。结果 83例口腔鳞癌组织标本中,Snail的表达率为89.2%,其中,高表达率为49.4%,低表达率为39.8%。口腔鳞癌组织中Snail的表达水平与患者的性别、年龄、肿瘤分化程度、肿瘤大小、临床分期及淋巴结转移之间在统计学上无显著性差异（P>0.05）。Snail表达水平与口腔鳞癌患者的复发之间有显著性差异（P＝0.003）。结论 口腔鳞癌患者癌组织中Snail的高表达与肿瘤复发及预后之间有一定相关关系。因此,Snail有可能作为口腔鳞癌患者复发和预后的预测指标。     

TEAD4与口腔鳞癌预后和细胞迁移侵袭的研究

目的:研究TEA转录因子4(TEAD4)在口腔鳞癌(OSCC)组织中的表达与临床病理参数、预后的关系。方法:免疫组化检测79例原发性OSCC标本和21例口腔正常上皮黏膜中TEAD4的表达水平,分析其与临床病理参数之间的关系。使用小干扰RNA(siRNA)转染沉默Cal27细胞内源性TEAD4,通过Western blot、qRT-PCR、划痕试验、Transwell侵袭等实验探究TEAD4沉默对OSCC细胞系Cal27迁移、侵袭的影响。结果:免疫组化结果显示TEAD4在OSCC组织中表达明显高于正常口腔黏膜(P<0.05)。TEAD4高表达与患者颈淋巴结转移、临床分期和患者总体生存率相关(P<0.05)。TEAD4沉默后Cal27细胞侵袭、迁移能力明显减弱。结论:TEAD4高表达与OSCC恶性表型及预后有关,参与OSCC细胞迁移、侵袭表型的调控。     

口腔黏膜下纤维性变癌变的病理及临床生物学行为回顾性研究

目的 回顾分析口腔黏膜下纤维性变(oral submucous fibrosis,OSF)癌变的临床特点、病理以及生物学行为特性,为其临床治疗提供理论依据和指导.方法 对经手术治疗的528例口腔黏膜鳞状细胞癌患者临床资料进行回顾性分析,将其分为OSF癌变组(133例)及非OSF癌变组(395例).对两组年龄、性别、发病部位、病理学分型、淋巴结转移率及术后复发率等进行比较分析.结果 OSF癌变组患者平均年龄(45.7±8.1)岁,低于非OSF癌变组(55.8±11.3)岁;OSF癌变组男女之比为32.3:1,高于非OSF癌变组(2.3:1);OSF癌变组淋巴转移率13.5%(18/133)、复发率39.1%(52/133),均高于非OSF癌变组[7.6%(30/395)、27.8%(110/395)].结论 OSF癌变平均发病年龄提前,男性居多,在临床上更具侵袭性和转移性的生物学行为,预后较差,在临床上应引起高度重视.     

Prognostic value of Ki67 from clinically and histologically ‘normal’ distant mucosa in patients surgically treated for oral squamous cell carcinoma: a prospective study

The frequent spread of oral squamous cell carcinoma (OSCC) has been explained by the persistence of genetically altered mucosa after surgery. This study examined whether clinically and histologically ‘normal’ mucosa distant from the primary tumour (from the opposite cheek) has an abnormal proliferative status, and whether this is associated with poor prognosis in terms of local recurrence or lymph node metastasis. The prospective study included 47 consecutive patients with OSCC. Disease-free survival endpoints were defined as the duration between surgical resection and the diagnosis of recurrence, lymph node metastasis, death or last follow-up. Proliferative status was evaluated by Ki67 expression. The mean Ki67 value (16.5 ± 8.9) in the distant mucosa was statistically higher than that in controls (8.8 ± 2.9). Abnormally high Ki67 values (>20%) were detected in 11 OSCC patients (23%). Multivariate analysis showed that Ki67 value in distant mucosa was a powerful independent prognostic factor, greater than tumour differentiation or clinical stage for the disease-free survival rate; it was statistically negative regarding local recurrence. Some patients surgically treated for OSCC have an abnormal proliferative status in areas distant from the primary tumour. The Ki67 value in these areas is a promising prognostic factor.     

The impact of lymph node density as a predictive factor for survival and recurrence of tongue squamous cell carcinoma

The oral tongue is considered the most frequently involved site in cases of oral squamous cell carcinoma (OSCC). Lymph node (LN) density, defined as the number of positive LNs divided by the total number of resected LNs, is considered an important prognostic factor in OSCC; however the cut-off point remains uncertain. A retrospective study was performed involving 104 patients who underwent a glossectomy procedure for oral tongue squamous cell carcinoma (OTSCC) between the years 2008 and 2018. LN density and other related prognostic factors, including pathological N-stage (pN), extranodal extension (ENE), perineural invasion (PNI), and depth of invasion (DOI), were investigated in relation to survival and recurrence rates. pN + stage, the presence of ENE, the presence of PNI, and increased DOI were found to be associated with increased LN density values, as well as lower patient survival and higher recurrence rates. The statistical analysis identified a cut-off point for LN density of 2.5%. In advanced stage disease, LN density values above 2.5% had a significant impact on the survival rate (P = 0.005), as well as the recurrence rate (P = 0.038). In conclusion, in addition to other previously known prognostic factors, LN density may serve as a strong prognostic factor for survival and recurrence in patients with advanced- and early-stage OTSCC.     

Expression of E-cadherin in cervical lymph nodes from primary oral squamous cell carcinoma patients

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in oral and maxillofacial region with poor prognosis. E-cadherin plays a key role in cell-to-cell adhesion. E-cadherin expression in the metastatic cervical lymph node, especially in the micrometastatic cervical lymph node has seldom been reported in OSCC patients. OBJECTIVE: To investigate the E-cadherin expression in cervical lymph nodes from OSCC patients as well as its clinical significance. DESIGN: Thirty-three OSCC patients were involved in this study; among them, there were 28 males and 5 females, the age ranged from 34 to 78 years (mean 58.8 years). The most suspicious metastatic cervical lymph node (total 99 lymph nodes) from three cervical regions of each OSCC patient was selected for detection of E-cadherin using routine pathological examination and immunohistochemistry. RESULTS: Increased E-cadherin expression in the metastatic cervical lymph nodes was detected, which was diagnosed by routine pathological examination using HE staining. However, in the micrometastatic cervical lymph node, E-cadherin expression was negative. The survival rate of OSCC patients correlated with decreased E-cadherin expression (P=0.001), N stage (P=0.024) and tumor recurrence (P<0.001). Tumor recurrence is the only independent factor on the prognosis (RR=20.83 and P=0.014). CONCLUSIONS: Decreased E-cadherin expression in cancerous tissue correlates with the poor prognosis of OSCC patients. Detection of E-cadherin expression is useful to confirm the cervical lymph node metastasis and maybe useless to detect the cervical lymph node micrometastasis; further studies are encouraged to reveal the detail mechanism of E-cadherin expression in formation of lymph node metastatic focus.     

FAS and ErbB2 expression in early local recurrent oral cancer

J Oral Pathol Med (2010) 39 176–181 Background: Local failure occurs in 13.9–62.6% and it is a well known indicator of poor prognosis in patients with oral squamous cell carcinoma (OSCC), despite aggressive treatments. The purpose of this study was to investigate the value of histopathology and molecular biomarkers in predicting the development of early local recurrence. Methods: This study included a total of 69 patients. There were 23 patients with early recurrent OSCC and 46 patients without local recurrence with the same clinical stage and tumor site, in a pair‐matched study design. Their charts were retrospectively analyzed. All surgical specimens of the primary tumors were evaluated according to the system proposed by Anneroth et al. and immunohistochemical for ErbB2 and FAS were performed. Results: A significant correlation of early local recurrence with grade of histological malignancy (more than 15 points) was observed (Fisher’s exact test, P = 0.03). Early local recurrence was also significantly associated with weak FAS expression and strong intracytoplasmic ErbB2 staining (Mantel–Haenszal chi‐square, P = 0.0038 and P = 0.0068, respectively). Histological grade of malignancy (more than 15 points) was also correlated with reduced survival (log‐rank, P = 0.06). Among the histopathological parameters, keratinization, pattern of invasion and inflammation were important for overall survival (log‐rank, P < 0.0001). Regarding the biomarkers, only FAS was significantly associated with overall survival (log‐rank, P = 0.0002). Moreover, a positive correlation of FAS and membrane ErbB2 expression with keratinization was noticed. Conclusion: Histopathological characteristics and the expression of FAS and ErbB2 carry prognosis importance in local recurrence and overall survival in OSCC.     

Oral squamous sell carcinoma in North-Eastern Hungary I. Epidemiology

The purpose of this study was to characterize the epidemiological data of oral squamous cell carcinoma (OSCC) patients in North-Eastern Hungary. The medical records of 119 randomly selected patients with OSCC admitted to the Department of Maxillofacial Surgery of the Faculty of Dentistry, University of Debrecen were reviewed. Cases were identified according to the epidemiological data, as to site, tumor size, lymph node involvement, clinical stage, histological differentiation, treatment obtained, recurrence of disease and survival rate. There was an obvious male predominance (male:female = 5.2:1). The median age at diagnosis was 57.4 years. The most common sites of OSCC were the floor of the mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the patients (58,8%) presented with early-stage (I-II) disease at the time of diagnosis, and 48.6% had moderately differentiated tumors. The most frequent therapeutic modality used was surgery with or with out of radiotherapy. Roughly one fifth of the cases (20.7%) experienced a recurrence of disease during the follow-up period. The overall 5-year survival rate was 38.7% (stage I: 68.3%, stage II: 31.0%, stage III: 22.6%, stage IV: 11.1%). There was a correlation between survival and tumor size, lymph node metastasis, clinical stage and surgical treatment (p < or = 0.05, respectively). We found no significant correlation between histological differentiation and survival. Clinical stage exerts the most strongly significant impact on survival. Therefore, early detection and proper surgical intervention enhance patients' survival most effectively.     

口腔鳞癌中VEGF和MMP-2的表达及其相关性

目的：探讨MMP-2、VEGF在口腔鳞状细胞癌（OSCC）中的表达、两者相关性及其作用。方法：采用免疫组化法检测MMP-2和VEGF在86例OSCC和20例正常非肿瘤组织中的表达情况及两者的相关性。结果：MMP-2和VEGF在OSCC中的阳性表达率分别为85．9％和88．4％，均高于正常组织的10．0％，15．0％；差异均有显著性差异如〈0．01）：MMP-2和VEGF在OSCC中的表达呈正相关（CAMMA值0．476，p=0．007）。结论：MMP-2和VEGF在OSCC中呈过表达，二者之间的相互作用与OSCC增殖、侵袭和转移密切相关。