EGFR在局部晚期口腔鳞癌中的表达及与TPF诱导化疗的关系

目的:探讨EGFR在晚期口腔鳞癌患者中的表达及与TPF诱导化疗的关系。方法:以256例局部晚期口腔鳞癌的前瞻性临床随机对照试验患者为研究对象,采用免疫组织化学方法,检测口腔鳞癌治疗前组织中EGFR的表达情况,分析其与临床病理各项指标的关系。采用SPSS 18.0软件包对数据进行统计学分析。结果:EGFR阳性表达强度与患者的年龄显著相关(P=0.015),未发现其与患者其他临床病理指标之间的显著相关性;在病理和临床疗效方面,EGFR阳性表达强度与TPF诱导化疗疗效无显著相关性。EGFR表达与口腔鳞癌患者的预后无显著相关,包括肿瘤复发、总体生存率、无瘤生存率、无肿瘤复发生存率和无肿瘤转移率。结论:EGFR的表达强度与患者的年龄相关,其在口腔鳞癌中的临床应用价值有待进一步研究。     

Cyclooxygenase-2-765G>C functional promoter polymorphism and its association with oral squamous cell carcinoma

Aim: Cyclooxygenase‐2 is a key enzyme in the conversion of arachidonic acid to prostaglandins, and has critical role in the progression of several malignancies, including oral squamous cell carcinoma. Methods: We designed a case‐control study to evaluate the susceptibility of the functional ?765G>C genetic variation in oral squamous cell carcinoma patients. Polymerase chain reaction‐based restriction fragment length polymorphism analysis was used to determine the polymorphism in oral squamous cell carcinoma (n = 150) patients and healthy controls (n = 150). Results: The genotype frequencies of cyclooxygenase‐2 765G>G, 765G>C, and 765C>C were 73.3%, 18.66%, and 8.0% in the cancer patients, and 94.66%, 4% and 1.3% in the controls, respectively. The cyclooxygenase‐2 GC and CC genotypes were significantly associated (P = 0.0003 and P = 0.01, respectively) with oral squamous cell carcinoma patients, when compared to the controls. The 765G>C genotypes were statistically significant, with habitual tobacco chewing and alcohol consumption + smoking (P = 0.05). Conclusions: This study highlights the genetic variant that might play a role in mediating susceptibility to oral squamous cell carcinoma in this population.     

Prediction of occult cervical lymph node metastasis in patients with stage I -II squamous cell carcinoma of the oral cavity

The presence of lymph node metastasis is the most important prognostic factor in oral cancer. The purpose of this study was to find useful markers for predicting occult cervical lymph node metastasis in patients with stage I or II squamous cell carcinoma of the oral cavity. We investigated 6 clinicopathologic factors and 2 genetic markers to predict late or occult cervical metastasis in 33 patients with stage I and II oral squamous cell carcinoma who underwent partial glossectomy through the mouth without elective neck dissection. In this study, we performed fluorescence in situ hybridization (FISH) with specimens obtained by fine-needle aspiration biopsies (FNA biopsies) of primary oral cancer material, to investigate numerical aberration of the gene. Late cervical lymph node metastasis occurred in 16 of the 33 patients (48.5%) during follow-up after treatment of the primary tumor. Factors significantly associated with the development of cervical metastasis were the mode of invasion (p = 0.009), cyclin D1 (p = 0.003) and EGFR numerical aberration (p = 0.024). The rate of disease-free survival from metastatic disease was significantly lower in patients with mode of invasion 4 C-4 D than in those with 1-3, and was significantly lower in patients with cyclin D 1 or EGFR gene numerical aberrations than in those without such aberrations (log rank test, p = 0.0064, p = 0.0016 or p = 0.0150). Our results indicate that patients with stage I - II squamous cell carcinoma of the oral cavity with the mode of invasion 4 C or 4 D, cyclin D 1 and EGFR gene numerical aberration should be considered a high-risk group for late cervical lymph node metastasis.     

Role of the MIR146A polymorphism in the origin and progression of oral squamous cell carcinoma

Gene expression and cell behavior are regulated by several factors, including small non‐coding RNAs. MicroRNAs affecting cell growth, differentiation, and apoptosis are thought to play an important role in tumorigenesis. The levels of miR‐146 appear to be associated with cancer development and progression, including that of oral squamous cell carcinoma. The aim of this investigation was to ascertain whether the single nucleotide polymorphism, rs2910164, mapping in the MIR146A gene, has a role in oral squamous cell carcinoma progression. A genetic association study was performed with a sample set of 346 oral squamous cell carcinomas collected in Italy. Our data indicate that the rs2910164 polymorphism is not associated with tumor development. However, a slight increase in the frequency of the variant allele was observed in Stage II tumors. Further investigations are needed to verify a possible role of the variant allele or rs2910164 in oral squamous cell carcinoma progression.     

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。     

复发性口腔鳞癌挽救性手术近期疗效

目的　探讨不同期复发性口腔鳞癌挽救性手术治疗的疗效。方法　对 30例首次复发的复发性口腔鳞癌患者临床再分期后行挽救性手术并跟踪随访。结果　复发性口腔鳞癌早期患者的总生存时间及无瘤生存时间均比复发进展期者长 ,且复发早期 1年生存率及 1年无瘤生存率均高于复发进展期。结论　对复发性口腔鳞癌进行临床的再分期有利于评价预后及制定治疗方案 ;挽救性手术是复发性口腔鳞癌的有效治疗手段 ,尤其对复发性口腔鳞癌早期的患者     

MiR-200c inhibited the proliferation of oral squamous cell carcinoma cells by targeting Akt pathway and its downstream Glut1

ObjectiveOur study aimed to investigate the functionality of miR-200c in oral squamous cell carcinoma.MethodsTumor tissues and adjacent tissues were obtained from oral squamous cell carcinoma patients, and blood samples were extracted from both oral squamous cell carcinoma patients and healthy controls. Expression of miR-200c in those tissues was detected by qRT-PCR. All patients were followed-up for 5 years and ROC curves as well as survival analyses were performed to evaluate the diagnostic as well as prognostic values of serum miR-200c for oral squamous cell carcinoma. miR-200c and Glut1 overexpression oral squamous cell carcinoma cell lines were constructed and cell proliferation was detected by CCK-8 assay. Glucose uptake was determined by glucose uptake assay. Interactions between miR-200c, Akt and Glut1 were explored by western blot.ResultsExpression of miR-200c was significantly downregulated in tumor tissues comparing with adjacent tissues in most oral squamous cell carcinoma patients. Serum level of miR-200c was lower in oral squamous cell carcinoma patients than that in healthy controls, and it was decreased with increased primary tumor stages. Serum levels of miR-200c can been used to effectively distinguish oral squamous cell carcinoma patients from healthy control, and patients with lower serum level of miR-200c showed shorter survival time. miR-200c overexpression inactivated Akt and Glut1 expression, while Akt activator and Glut1 overexpression showed no significant effects on miR-200c. Akt activator promoted Glut1 expression, but Glut1 overexpression showed no significant effects on Akt. MiR-200c inhibited cell proliferation and glucose uptake, while Akt activator and Glut1 overexpression reduced the inhibitory effect of miR-200c overexpression on cell proliferation.ConclusionmiR-200c can inhibit the proliferation of oral squamous cell carcinoma cells by targeting Akt pathway and its downstream Glut1.     

Clinical behavior of T1–T2 squamous cell carcinoma of the oral cavity

ObjectivesThe main aim of the present study is to analyze the differences in the clinical behavior of pT1 and pT2 oral squamous cell carcinoma of the oral cavity and the importance of tumor thickness in these groups of patients.MethodsA retrospective analysis was conducted using the records of patients diagnosed with pT1 and pT2 oral squamous cell carcinoma between 2006 and 2015 to identify significant differences between these two groups of patients. Several pathological features such as T-stage, N-stage, tumor thickness, surgical margins, and locoregional failure were analyzed.Results194 patients were included in this study. Tumor thickness >0.4 cm was significantly related with nodal involvement and overall survival (p < 0.001). T and N stage, tumor thickness, extracapsular spread and surgical margins were associated with poorer outcomes in terms of overall survival (p < 0.001).ConclusionTumor thickness represents an extremely important prognostic factor and to include depth of invasion (DOI) in the staging of oral squamous cell carcinoma will help in the choice of better treatment strategies and to improve overall survival.     

Impact of interleukin-8 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan

Oral Diseases (2012) 18 , 307–314 Objectives: Interleukin‐8 (IL‐8), which is an angiogenic chemokine with a high expression level in tumor tissues, plays important roles in developing many human malignancies including oral squamous cell carcinoma (OSCC). This study was designed to examine the association of IL‐8 gene polymorphisms with the susceptibility and clinicopathological characteristics of OSCC. Methods: A total of 270 patients with OSCC and 350 healthy control subjects were recruited. Four single nucleotide polymorphisms (SNPs) of IL‐8 genes were analyzed using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) genotyping analysis. Results: Results showed that four IL‐8 SNPs (?251 T/A, +781 C/T, +1633 C/T, and +2767 A/T) were not associated with oral cancer susceptibility as well as clinicopathological parameters. But among 345 smokers, IL‐8 polymorphisms carriers with betel quid chewing were found to have a 17.41‐ to 23.14‐fold risk to have oral cancer compared to IL‐8 wild‐type carriers without betel quid chewing. Among 262 betel quid chewers, IL‐8 polymorphisms carriers with smoking have a 10.54‐ to 20.44‐fold risk to have oral cancer compared to those who carried wild type without smoking. Conclusions: Our results suggest that the combination of IL‐8 gene polymorphisms and environmental carcinogens might be highly related to the risk of oral cancer.     

口腔鳞癌中Shh/Gli1的表达及其临床生物学意义

目的：明确Hedgehog信号通路关键分子Shh及Gli1在口腔鳞癌中的表达情况,并初步探讨其与口腔鳞癌临床生物学的关系及对预后的影响。方法：采用免疫组织化学方法分别检测35例正常口腔黏膜及35例口腔鳞癌中Shh和Gli1的表达及细胞内定位情况。采用SPSS11.0软件包对Shh、Gli1的表达与口腔鳞癌患者的各项临床病理参数进行非参数统计分析,应用生存表法分析Shh及Gli1的表达水平与口腔鳞癌患者预后的关系。结果：Shh及Gli1在35例正常黏膜中均无表达,在口腔鳞癌组织中Shh的阳性率为60%,Gli1胞质、胞核阳性率分别为54.3%及42.9%,与正常黏膜相比差异显著（P〈0.05）。非参数分析显示,Shh的表达水平与口腔鳞癌患者的肿瘤大小及临床分期显著相关（P〈0.05）;生存分析表明,Shh的表达水平与口腔鳞癌患者预后相关,高表达的口腔鳞癌患者预后较差（P〈0.05）。Gli1的表达水平与口腔鳞癌患者预后不相关。结论：Hedgehog信号通路的主要配体Shh及核转录因子Gli1在口腔鳞癌中有不同程度的表达,其中Shh的表达水平与肿瘤大小、临床分期及患者预后明显相关,提示Hedgehog信号通路的异常激活在口腔鳞癌中发挥一定的作用。     

Specimen‐driven intraoperative assessment of resection margins should be standard of care for oral cancer patients

With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five‐year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on locoregional control and survival. It is not uncommon that the resection margins of oral tumors are inadequate. However, when providing the surgeon with intraoperative feedback on the resection margin status, it is expected that obtaining adequate resection margins is improved. In this respect, it has been shown that specimen‐driven intraoperative assessment of resection margins is superior to defect‐driven intraoperative assessment of resection margins. In this concise report, it is described how a specimen‐driven approach can increase the rate of adequate resections of oral cavity squamous cell carcinoma as well as that it is discussed how intraoperative assessment can be further improved with regard to the surgical treatment of oral cavity squamous cell carcinoma.     

Marginal and segmental mandibulectomy in patients with oral cancer: a statistical analysis of 106 cases.

PURPOSE: The treatment of oral squamous cell carcinoma may require mandibular resection to secure adequate margin. This bone resection often is segmental or marginal mandibulectomy. The purpose of this work was to evaluate the local control and survival after surgical treatment of oral cancer, according to these 2 different mandibular resection procedures. PATIENTS AND METHODS: We conducted a retrospective study of a 20-year cohort of 106 patients who underwent marginal or segmental mandibulectomy for oral cancer. All patients had a biopsy-confirmed diagnosis of squamous cell carcinoma involving either the floor of the mouth, mandibular gingiva, retromolar trigone, tongue, buccal mucosa, or oropharynx. The type of mandibular resection and treatment outcome were compared, using an univariate analysis by the Pearson chi(2) test, logistic regression model for multivariate analysis, and Kaplan-Meier method to determine survival. RESULTS: The 5-year observed survival rate was 60.35%. The presence of histologic mandibular invasion increased the local recurrence rate. Early tumor stages (P =.02) were found to be associated with decreased local recurrence rates. Our findings indicate that tumor stage and size of mandibulectomy are more important than the type of mandibulectomy in predicting histologic bone involvement. The cases treated with a greater than 4 cm bone resection showed a lower survival rate than those treated with less than 4 cm mandibulectomy (P =.01). Patients in advanced stages (P =.006) and those with surgical margin (P =.0001) or the bone (P =.003) affected by the tumor showed a statistically significant lower survival rate. However, no statistically significant differences were found between patients treated by marginal or segmental mandibulectomy. CONCLUSIONS: Among the prognostic factors studied, the status of the surgical resection margin, the bony involvement and the size of mandibulectomy affected the prognosis for oral carcinoma. Mandibular conservation surgery is oncologically safe for patients with squamous carcinoma in early stages. The marginal technique was not associated with worse prognosis.     

口腔鳞癌组织中doc1基因mRNA表达的意义

目的:doc1基因的转录产物p12蛋白与肿瘤的发生、发展密切相关.本研究旨在检测doc1基因mRNA在不同分化的口腔鳞状细胞癌中的表达,探讨其在口腔鳞状细胞癌组织中表达的意义.方法:用半定量RT-PCR方法检测30例口腔鳞状细胞癌和20例正常口腔黏膜中doc1基因mRNA的表达,并分析doc1基因mRNA表达量与临床病理特征的关系.结果:doc1基因mRNA在高、中、低分化口腔鳞状细胞癌中的灰度平均值为:1.35±0.04,1.20±0.05,1.08±0.03;正常口腔黏膜上皮doc1 mRNA的灰度平均值为:1.58±0.15,表达高于口腔鳞状细胞癌组织,两者之间的差异具有显著性意义,高中低分化的口腔鳞状细胞癌两两比较,均有统计学差异.结论:doc1基因可能在口腔鳞状细胞癌早期具有重要作用,doc1 mRNA低表达可能是口腔鳞状细胞癌中的早期事件.     

STAT3 mRNA、EGF mRNA和EGFR mRNA在口腔鳞癌组织中的表达及意义

目的：探讨STAT3 mRNA、EGF mRNA和EGFR mRNA在口腔鳞状细胞癌组织中的表达及其临床意义。方法：采用原位杂交法检测60例口腔鳞癌患者的癌组织、30例不典型增生组织及60例正常口腔黏膜组织中STAT3 mRNA、EGF mRNA和EGFRmRNA的表达,并结合病理分级、有无淋巴结转移等临床指标进行统计学分析。结果：在口腔鳞癌癌变过程中STAT3、EGF和EGFRmRNA的表达在正常口腔黏膜组织、不典型增生组织及癌组织中的表达率均依次增高,分别为25.0%（15/60）、40.0%（12/30）、68.3%（41/60）和33.3%（20/60）、43.3%（13/30）、80.0%（48/60）及18.3%（11/60）、46.7%（14/30）、75.0%（45/60）,组间比较差异有统计学意义（P〈0.05）。在口腔鳞癌组织中STAT3表达与癌的组织学分级、浸润深度及淋巴结转移密切相关（P〈0.05）;EGF表达与癌的组织学分级、浸润深度及淋巴结转移密切相关（P〈0.05）;EGFR表达与癌的组织学分级、浸润深度及淋巴结转移密切相关（P〈0.05）。口腔鳞癌中STAT3、EGF和EGFR mRNA的表达具有相关性。结论：STAT3、EGF和EGFR mRNA可能在口腔癌的浸润、转移及黏膜上皮癌变过程中起重要作用,STAT3、EGF和EGFR mRNA的联合检测可望成为口腔鳞癌早期诊断和判断预后的客观指标之一。     

Invasive front in oral squamous cell carcinoma: image and flow cytometric analysis with clinicopathologic correlation

OBJECTIVE: Pathologists have drawn attention to the invasive tumor front (ITF) in the determination of the biologic aggressiveness of oral cancer. We have attempted to discover the prognostic significance of cancer cells with abnormal DNA content at the ITF of oral squamous cell carcinoma. STUDY DESIGN: A comparative DNA analysis by means of image cytometry and flow cytometry was conducted to confirm the usefulness of image cytometry in detecting cancer cells having abnormal DNA content at the ITF. The prognostic value of cancer cells with abnormal DNA content ws examined by a multivariate analysis for 195 patients with oral squamous cell carcinoma. RESULTS: In the comparative DNA analysis, it was suggested that image cytometry is useful for detecting cancer cells with abnormal DNA content (4c exceeding rate [4cER]), which is associated with poor prognosis of patients with oral squamous cell carcinoma. In the multivariate analysis, 3 independent factors were found to significantly influence cause-specific survival. These are, in decreasing order of influence, (1) abnormal DNA content (4cER), (2) clinical stage, and (3) growth type. CONCLUSION: The presence of cancer cells with abnormal DNA content of the ITF in conjunction with clinical findings (clinical stage and growth type) can give additional useful information when selecting treatment strategies for oral cancer patients.     

口腔鳞状细胞癌患者血清TSGF、SCC-Ag、CEA的表达及其临床意义

目的　探讨联合检测血清中恶性肿瘤特异性生长因子(TSGF) 、鳞状细胞癌抗原(SCC-Ag)及癌胚抗原（CEA）在口腔鳞状细胞癌诊断中的价值。方法　采集58例口腔鳞状细胞癌患者、36例口腔良性肿瘤患者及30例健康人血液,分别检测血清中TSGF、SCC-Ag和CEA含量。结果　口腔鳞状细胞癌组TSGF、SCC-Ag、CEA含量明显高于口腔良性肿瘤组和健康组(P< 0.05)。口腔鳞状细胞癌组TSGF、SCC-Ag、CEA阳性率分别为74.14%、55.17%、24.14%,联合检测阳性率为86.21%。结论　血清TSGF、SCC-Ag、CEA分别检测对口腔鳞状细胞癌的诊断有一定意义,联合检测提高口腔鳞状细胞癌的诊断率。     

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....     

Expression of carbonic anhydrases I/II and the correlation to clinical aspects of oral squamous cell carcinoma analyzed using tissue microarray

J Oral Pathol Med (2012) 41 : 533–539 Background: Carbonic anhydrases (CA), a family of metalloenzymes, play an important role in catalyzing the equilibration of carbon dioxide (CO₂) and carbonic acid (H₂CO₃). The role of CAs in tumorigenesis is controversial, especially regarding the expression of CA isoenzymes between various tumor types. This study explores the correlation between the expressions of CA I and CA II and the characteristic features of oral cancer. Methods: We immunohistochemically examined the expressions of CA I and CA II in 279 cases of oral squamous cell carcinoma (OSCC) using tissue microarrays. Additionally, the oral cancer cell line SCC‐9 was used to confirm the relationship between CA I and CA II expression and cell growth. Results: We found a significant correlation between positive CA I and CA II stains and OSCC for more advanced clinical stage (P = 0.014 or 0.012) and larger tumor size (P = 0.008 or 0.038), but not for positive lymph node metastasis, distal metastasis, and recurrence. In vitro analysis also showed that treatment with a CA inhibitor, acetazolamide, inhibited the growth of SCC‐9 cells. Conclusion: We conclude that expressions of CA I and CA II in OSCC samples can be used to predict local tumor growth in OSCC patients.     

TGFβ1mRNA在颌骨骨折愈合过程中的表达及意义

为了进一步探讨ＴＧＦβ在骨生长和骨愈合中的作用，建立了颌骨骨折愈合的动物模型，利用原位杂交方法检测骨折愈合过程中ＴＧＦβ１ｍＲＮＡ的表达。结果发现，在骨折愈合过程中的软骨形成和膜内骨骨化阶段，ＴＧＦβ１的转录水平较高，在膜内成骨时转录水平较低，而在伤后即刻反应阶段无ＴＧＦβ１的转录。说明ＴＧＦβ在骨折修复过程中最初的形态发生，随后的细胞增殖及最终的组织重建中起着重要的作用。