The relationship of the histologic grade at the deep invasive front and the expression of Ki-67 antigen and p53 protein in oral squamous cell carcinoma

BACKGROUND: Although many histopathologic characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, accurate, and unequivocal factors have not been clearly identified. The purpose of this study was to evaluate a potential association between the histologic grade of malignancy at the deep invasive front and the expression of Ki-67 antigen and p53 protein in O-SCC. METHODS: The expression of Ki-67 antigen and p53 at the invasive tumor front area of O-SCC was examined by immunohistochemistry of archived tissue from 62 cases. The mean age of patients was 60.7 years (range: 37-89) and the male-female ratio was 1.6:1 (38 men, 24 women). There were 20, 17, 14, and 11 cases classified as stage I to stage IV, respectively. The correlation between the intensity of immunostaining for Ki-67 antigen and p53 and the histologic grade of malignancy at the deep invasive front (invasive front grade, IFG) was analyzed. The expression of Ki-67 antigen and p53 in normal oral epithelia (10 cases) was also investigated. RESULTS: The mean Ki-67 labeling index (LI) in the O-SCC samples was 32.8 +/- 12.0% (n = 62). The mean total score of IFG (IFG score) was 9.1 +/- 2.7 points (n = 62). There was a significant linear correlation between the IFG score and the Ki-67 antigen (gamma = 0.651, R2 = 0.596, P < 0.0001). Of 50 tumors examined, 27 (54.0%) exhibited p53-positive nuclear immunostaining. The staining patterns for Ki-67 antigen and p53 were similar. Both Ki-67-LI and p53-positive status were significantly correlated with the IFG scores. CONCLUSION: The findings of this study demonstrate that overexpression of Ki-67 antigen and p53 at the deep tumor invasive front of O-SCC is associated with histologic grade of malignancy.     

SUZ12在舌鳞癌中的表达及临床意义

目的　研究多梳蛋白家族成员SUZ12在舌鳞状细胞癌（以下简称舌鳞癌）中的表达及其与多种临床病理参数之间的关系,探讨其在舌鳞癌预后判断中的意义。方法 采用免疫组织化学染色半定量的方法检测72例术前未接受放、化疗或其他特殊治疗的原发性舌鳞癌患者标本及15例正常舌黏膜中SUZ12的表达情况,结合临床资料,对其与舌鳞癌临床病理特征和预后的相 关性进行统计学分析。结果 SUZ12在舌鳞癌组中的表达明显高于正常舌黏膜。舌鳞癌组织中SUZ12的表达与患者年龄、性别、抽烟、饮酒、肿瘤大小、病理分级、临床分期之间在统计学上无显著性差异,与颈部淋巴结转移（P=0.0325）、总体生存率（P=0.0225）及无瘤生存率（P=0.0179）相关。结论 SUZ12在舌鳞癌组织中过表达与颈淋巴结转移及低生存率相关,可能作为舌鳞癌诊断和预后判断的指标。     

口腔鳞癌腮腺淋巴结转移的临床病理特征与预后分析

目的:探讨口腔鳞癌患者腮腺淋巴结转移的临床病理特征及预后影响因素.方法:回顾性分析2003年1月—2017年12月上海交通大学医学院附属第九人民医院收治的60例伴或不伴腮腺淋巴结转移的口腔鳞癌患者的临床病理资料及影像学资料,分析其临床病理和影像学特征及其与预后的相关性.采用SPSS 23.0软件包对数据进行统计学分析....     

早期舌癌不同颈部处理方式对无病生存率影响的多因素分析

目的探讨影响T1/T2N0M0期舌鳞癌患者无病生存率的影响因素,比较不同颈部处理方式对无病生存率的影响。方法回顾性调查97例舌癌患者的住院病历和随访记录,采用Cox比例风险模型对性别、年龄、T分期、原发灶治疗方式、颈部处理方式和肿瘤细胞分化程度共6个可能影响患者无病生存率的因素进行筛选,Kaplan-Meier法对各影响因素进行生存率分析并计算生存率,log- rank法比较各因素不同水平生存分布的差异。重点考察不同颈部处理方式对生存率的影响。结果T分期、原发灶治疗方式、颈部处理方式和细胞分化程度是影响患者无病生存率的主要因素,其P值分别为P<0.001、P=0.04、P=0.003、P<0.001,相对风险率分别为4.387、0.496、0.504、2.620。各有影响因素下不同水平间的无病生存率有统计学差异（ P<0.05）。结论cN0患者颈部不同处理方式对患者无病生存率有明显影响,颈淋巴清扫术加放疗可减少复发风险49.6%;TNM分期对早期舌癌预后有良好的描述能力。     

Prognostic value of response to preoperative chemoradiotherapy and residual tumor grades in tongue carcinoma

OBJECTIVE: The purposes of the present study were to analyze our experience with preoperative chemoradiotherapy followed by surgery for advanced tongue carcinoma and to assess the prognostic value of response to preoperative therapy in these tumors.Study Design: Between May 1988 and December 1999, a total of 43 patients with advanced but potentially resectable squamous cell carcinoma of the tongue were candidates for this study. A minimum tumor size of 3 cm was required. The mean age was 59.8 years (range, 26-85 years); 13 cases were advanced stage II, 23 cases were stage III, and 7 cases were stage IV. All patients were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy; 2-6 weeks later, they underwent curative surgery. Tumor regression rate, residual tumor grade, and histologic regression grade to the preoperative therapy were analyzed to determine their influence on the prognosis. RESULTS: With a median follow-up of 60.5 months, overall survival rates were 86.0% for all cases, 92.3% for stage II cases, 77.3% for stage III cases, and 100% for stage IV cases. The progression-free survival rates according to tumor regression rate were 33.3% for group 1 (< 50% tumor regression), 66.7% for group 2 (> or = 50% and < 75% regression), 100% for group 3 (> or = 75% and < 100% regression), and 96.0% for group 4 (complete regression). The higher the tumor regression rates, the higher the survival rates. When patients who achieved a regression rate of 75% or higher were compared with those who did not, there was a significant difference in survival (P < .0001). The factors of residual tumor grade and histologic regression grade also had good correlations with the prognosis (residual tumor grade, P =.0324; histologic regression grade, P < .0001). CONCLUSIONS: The findings of the present study suggest that response to preoperative chemoradiotherapy, such as tumor regression rate, residual tumor grade, and histologic regression grade, could be of prognostic value in patients with tongue carcinoma.     

舌鳞状细胞癌浸润前沿细胞增殖的研究

目的　研究舌磷癌浸润前沿分级、检测增殖细胞核抗原 (PCNA)、Ki6 7、核仁组织区相关嗜银蛋白 (AgNOR)在浸润前沿中的表达。 方法　对 5 7例舌鳞癌行浸润前沿分级 ,采用免疫组化SP法及银染色法检测浸润前沿和中心PCNA、Ki6 7、NORs的表达。结果　浸润前沿PCNA、Ki6 7的表达和AgNOR均数均明显高于非前沿部分 ,差异有极显著性 (P <0 .0 0 1) ;浸润前沿PCNA标记指数 (P <0 .0 5 )、AgNOR均数 (P <0 .0 1)与浸润前沿分级 (IFG)总分呈正相关关系 ;单因素COX分析显示 ,IFG总分 (P <0 .0 1)、浸润前沿AgNOR均数 (P <0 .0 5 )对判断预后有意义 ;多因素COX分析显示 ,IFG总分 (P <0 .0 1)可作为预测总体生存率和累积生存率的有意义的因子。结论　舌鳞癌浸润前沿肿瘤细胞分化较差 ,增殖活性明显高于非前沿部分 ;IFG总分和浸润前沿AgNOR均数与舌癌预后有关     

临床病理因素对舌癌病人生存期的影响

目的　分析评价临床病理因素对舌癌病人生存期的影响。方法　回顾随访 86例本院治疗的舌鳞癌病例 ,对 TNM分期、吸烟饮酒、治疗方法、病理分化、肿瘤浸润方式、浸润深度、瘤细胞分裂计数、淋巴细胞浸润、淋巴结转移、复发等因素与舌癌相关 5年生存率的关系进行单因素和 Cox多因素的分析。结果　舌癌相关 5年生存率为 70 .9% ,单因素分析中 ,只有 T分期和吸烟饮酒未发现对生存率有显著影响 (P>0 .0 5 ) ,多因素分析则只有病理检出淋巴结转移和术后局部复发 (P<0 .0 1)以及术前化疗、病理分化 (P<0 .0 5 )显著影响生存率。结论　淋巴结转移和局部复发是舌癌病人预后恶化的重要原因 ,平阳霉素化疗加手术的治疗方法可改善预后     

口腔癌的临床病理特征与预后

口腔鳞状细胞癌占口腔恶性肿瘤的90％以上，恶性程度较高，寻找与其预后相关的因素有利于肿瘤的治疗和预后评估。目前的研究发现，一些临床病理指标在预测口腔癌的预后中具有一定价值。在与肿瘤大小有关的因素中，肿瘤厚度（侵袭深度）是唯一具有独立预后价值的指标；对肿瘤侵犯前沿进行组织学分级，在预测淋巴结转移、局部复发、生存率方面的价值显著高于传统的对整个肿瘤的组织学分级；肿瘤手术切缘状况与肿瘤复发、患者生存率相关，但安全手术切缘的界定标准尚有待统一；肿瘤是否有淋巴结转移、淋巴结转移程度特别是肿瘤的淋巴结包膜外浸润在预测肿瘤复发、远处转移、生存率方面具有重要意义。     

EMMPRIN expression in tongue squamous cell carcinoma

Background:  Extracellular matrix metalloproteinase inducer (EMMPRIN) is identified as a tumor-cell membrane protein that stimulates matrix metalloproteinases (MMPs) production. Several studies have shown that higher EMMPRIN expression is associated with shorter survival time and correlated significantly with more advanced clinico-parameters of cancer. The aim of this study was to investigate the relationship between clinico-pathologic characteristics and EMMPRIN, and prognostic significance of EMMPRIN expression in human tongue squamous cell carcinoma.
Methods:  Extracellular MMP inducer expression was examined immunohistochemically on paraffin-embedded tissue specimens from 68 patients with tongue squamous cell carcinoma and who underwent radical surgeries from 1996 to 2006. The 68 patients were followed up from 1 to 119 months, with an average of 27.5 months. Nonparametric tests were performed for the comparison of EMMPRIN expression between two independent groups. Survival analysis was performed to find the prognostic significance of EMMPRIN expression.
Results:  We found that EMMPRIN expression in tongue squamous cell carcinoma is significantly higher than that in non-cancerous epithelium adjacent to carcinoma of tongue. In addition, EMMPRIN expression is significantly associated with tumor diameter and clinical stage in the samples, but did not correlate with gender, age, tumor metastasis, and pathological grade. Finally, survival analysis indicates that EMMPRIN overexpression correlates significantly with poor overall survival in the patient cohort.
Conclusion:  These results suggest that EMMPRIN might represent an attractive target for immunotherapeutic approaches in a subgroup of patients with tongue squamous cell carcinoma.     

cN0期舌鳞癌患者颈淋巴结转移的相关因素及预后分析

目的: 探讨cN0期舌鳞癌患者颈淋巴结转移的相关因素及术后生存质量,为临床预测颈部隐匿性转移及提高生存率提供理论依据。方法: 收集南京医科大学附属淮安第一医院cN0期舌鳞癌患者283例,通过卡方检验及Logistic回归分析颈淋巴结转移与患者临床病理参数之间的相关性,通过单因素及多因素Cox回归分析探讨舌鳞癌患者预后的独立危险因素,通过生存分析研究颈淋巴结转移与患者预后之间的相关性。采用SPSS 21.0软件包对数据进行统计学分析。结果: 卡方检验及Logistic回归分析表明,浸润深度、T分期、病理学分级与颈淋巴结转移密切相关（P<0.05）,而浸润深度是导致术后颈淋巴结转移的主要因素（OR=2.175）;浸润深度、病理分级及颈淋巴结转移与舌鳞癌患者预后密切相关（P<0.05）。结论: 浸润深度、T分期、病理学分级可作为预测cN0期舌鳞癌隐匿性颈淋巴结转移的指标,浸润深度、病理分级及颈淋巴结转移可作为预测cN0期舌鳞癌患者预后的指标。     

Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma

BACKGROUND: Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. METHODS: The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90 years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I-IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. RESULTS: Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant (P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity (P = 0.0138). CONCLUSION: This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC.     

Prediction of delayed neck metastasis in patients with stage I/II squamous cell carcinoma of the tongue

BACKGROUND: The incidence of delayed neck metastasis (DNM) in patients with squamous cell carcinoma (SCC) of the tongue is reported to be 20% to 50%. Although clinically negative cervical lymph nodes (N0) are associated with a good outcome, the prognosis is poor in patients with DNM. The aim of this study was to evaluate the clinicopathological and immunohistochemical parameters associated with DNM in patients with stage I/II SCC. METHODS: Fifty nine patients, with previously untreated stage I/II carcinoma, underwent examination of clinicopathological and immunohistochemical parameters and incidence of DNM. A linear discriminant analysis was used to analyze prognostic factors and to determine the probability of DNM occurring. RESULTS: DNM occurred in 14 (24%) subjects of the 59 study patients, level I to level III, within 5 years. Parameters such as gender and age, disease stage, tumor size and histological grade, tumor location, degree of tumor invasion and expression of VEGF, E-cadherin or Ki-67 showed no significant correlation with the occurrence of DNM; however, factors such as tumor morphology, tumor thickness greater than 4 mm, and Flt-4 expression were significantly associated with development of DNM. CONCLUSIONS: Such factors provide useful information with regard to DNM and the prognosis. We concluded that patients with early SCC whose tumors are > 4 mm in thickness and immunopositive for Flt-4 are particularly at risk of developing DNM.     

舌鳞状细胞癌患者血清VEGF水平的定量分析(英文)

目的 血管生成是肿瘤发生、发展和转移过程中的关键步骤。最近,许多血管生成因子陆续被分离出来。血管内皮生长因子（VEGF）是其中的一种,对血管内皮细胞的有丝分裂具有选择性作用。本研究目的是检测舌癌患者血清中VEGF含量,并探讨其与舌癌的临床病理特征及预后的关系。方法 研究对象包括10名正常献血员和31名舌癌患者。采用双抗体夹心法 ELISA定量检测血清中 VEGF浓度。结果处理采用独立样本t检验（independent-samples t test）。结果 正常对照组血清中VEGF的平均浓度为148.80±64.17pgml-1（范围,59～231pg.ml-1）,舌癌患者血清中VEGF的平均浓度为567.97±338.17pgml-1（范围,136～1892pg·ml-1）,两者之间的差异具有显著性（P<0.001）。舌癌患者血清中VEGF水平的高低与转移和临床分期密切相关（P<0.05）,而与性别和肿瘤的分化程度无关（P>0.05）。 结论 VEGF水平升高是舌癌发生、发展和转移的重要原因。检测舌癌患者血清中VEGF含量有助于判断有无转移及预后。     

Immunohistochemical expression of secreted frizzled receptor protein 1 in the invasive front of tongue squamous cell carcinoma

The Wnt signalling pathway is involved in the development of oral cancer. When inactivated, secreted frizzled receptor protein 1 (SFRP1), a cellular Wnt‐inhibitor protein, may enhance cancer development. The aim of this study was to assess the expression of SFRP1 in the invasive front of tongue squamous cell carcinoma (SCC). Immunohistochemical expression of SFRP1 in the cohesive and discohesive invasive front of 36 resection specimens of tongue SCC was investigated. Immunostaining was compared with tumour size, tumour thickness, and neural invasion. Immunoreactivity increased in depth from the surface of the tumour to the invasive front. There was a statistically significant association between type of invasive front and pattern of SFRP1 expression. A discohesive invasive front showed more intense immunoreactivity. No statistically significant associations were found between the intensity of staining and relevant prognostic factors. Tongue SSC has variable SFRP1 expression in different parts of the tumour and the greatest expression is in the invasive front. The more intense staining in the discohesive invasive front compared with the cohesive invasive front might contribute to the worse prognosis of cancers with a discohesive invasive front.     

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.     

Expression of heat shock proteins in squamous cell carcinoma of the tongue: an immunohistochemical study

Ito T, Kawabe R, Kurasono Y, Hara M, Kitamura H, Fujita K, Kanisawa M: Expression of heat shock proteins in squamous cell carcinoma of the tongue: an immunohistochemical study. J Oral Pathol Med 1998; 27: 18–22. © Munksgaard, 1998.
Twenty-four specimens of squamous cell carcinoma of the tongue were immuno-stained for heat shock proteins (HSPs) to reveal differences in stainability among normal epithelium, dysplasia and carcinoma and to clarify the prognostic significance of HSPs in comparison with survival period, clinical stage, lymph node metastasis, histological grade, and p53 immunostaining. Normal epithelium was positively stained in the suprabasal layer for HSP60 and HSP70, but was negative for HSP27 and HSP90. Dysplastic lesions were positive for HSP27, HSP70 and HSP90, but stained variously for HSP60. In squamous cell carcinoma, the cytoplasm of suprabasal tumor cells was often positive for HSP27 and HSP90 (18/24, 17/24, respectively). Although HSP immunohistochemistry has revealed changes in HSP expression during tumorigenesis of squamous epithelium of the tongue, there was no correlation between HSP staining and survival period, stage, lymph node metastasis, histological grade or p53 immunostaining.     

口腔黏膜鳞癌术后复发相关因素的观察和研究

目的：分析影响口腔鳞癌预后及复发的临床病理因素,为进行综合治疗及其预后评价提供临床依据。方法：对407例原发口腔鳞癌患者以病变部位、肿瘤厚度、临床T分期、区域淋巴结转移、治疗方式、手术方式、术后组织学分级等指标研究与口腔鳞癌术后及复发相关的因素。结果：口腔鳞癌术后的复发率与病变部位、肿瘤厚度、临床T分期、区域淋巴结转移及组织学分级等因素有关,诱导化疗联合手术的综合治疗可有效降低口腔鳞癌的复发率。结论：临床工作中,我们应综合分析各种临床病理因素,对与术后复发关系较为密切的因素进行仔细评估,制定出有效的预防措施,提高口腔鳞癌的手术治愈率及生存率,降低复发率。     

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低表达组和高表达组患者肿瘤复发、颈淋巴结转移、隐匿性淋巴结转移及生存率比较,均存在明显差异(P<0.05)。Cox风险回归模型结果显示,UHRF1的表达水平是影响口腔鳞癌患者生存率的危险因素(P=0.002)。结论 UHRF1在口腔鳞癌肿瘤组织中高表达,其表达水平与患者的临床预后密切相关,可作为口腔鳞癌有价值的预后指标。     

The value of histological grading of biopsy and resection specimens in early stage oral squamous cell carcinomas

Introduction

In oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival.

Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue

BACKGROUND: Osteopontin (OPN) expression in squamous cell carcinoma (SCC) of the tongue has not been clearly elucidated. METHODS: We selected 46 cases of tongue SCC and investigated the expression of OPN by immunohistochemical staining. The immunopositive reaction and score for each case were semiquantitatively evaluated. RESULTS: Scores were significantly higher in carcinoma nests than in neighboring normal epithelium or epithelial dysplasia. The OPN was expressed clearly in the cytoplasm of carcinoma cells. In cases of early invasive carcinoma, in particular, expression of OPN showed a remarkable increase at the invasion front compared with the non-invaded regions. However, there was no significant correlation between expression of OPN in the primary tumor nest and lymphatic metastasis, recurrence, or survival rate. CONCLUSION: This suggests that OPN is a useful biomarker of early invasion by SCC in tongue.