头颈鳞癌的DNA等位基因微卫星不稳定性分析

DNA等位基因微卫星不稳定性（microsatelliteinstability,MSI）广泛参与肿瘤的发生与发展,是肿瘤常见的遗传学改变之一。某些染色体或某一染色体的某些特定区域在头颈鳞癌（headandnecksquamouscellcarcinoma,HNSCC）发生发展中存在着高频发的MSI。有些MSI常发生于HNSCC的早期。弄清这些与HNSCC有良好相关性并与许多抑癌基因紧密连锁的微卫星有否等位基因缺失或不稳定性将有助于进一步阐明HNSCC的发生与发展机制。     

微卫星不稳定和错配修复基因异常在喉鳞状细胞癌中相关性研究

目的 研究喉鳞状细胞癌中微卫星不稳定（microsatellite instability,MSI）发生的临床意义及其与错配修复基因（mismatch repair gene,MMR）表达的相关性。方法 50例喉鳞状细胞癌患者的石蜡切片选自北京同仁医院2002年至2003年的手术标本,利用显微切割-多聚酶链反应-单链长度多态性分析-银染的方法进行MSI的检测,统计MSI的发生率及其与临床资料的相关性,应用免疫组织化学观察MMR中hMLH1和hMSH2的表达。五个微卫星位点位于染色体1P,3p,5q,9p,17p上,分别临近BCAR3（breast cancer anti-estrogen resistance3）,FHIT,APC,CDKN2A（p16）,TP53等基因。结果 在五个微卫星位点（D17S796,D3S3544,D5S656,D1S375,D9S162）提供统计信息的病例数分别是44,42,45,44和40例。MSI的发生率低于杂合性缺失（loss of heterozygosity,LOH）的发生率。MSI的发生率分别是：D17S796（TP53）20．5％（9／44）,D3S3544（FHIT）14．3％（6／42）,D5S65631．1％（14／45）,D1S375（BCAR3）20．5％（9／44）,D9S162（CDKN2A）15．0％（6／401。MSI的发生与年龄、性别、吸烟史、肿瘤部位、肿瘤分化、TNM分期的关系没有统计学意义（P〉0．05）,但是与肿瘤复发的相关性具有统计学意义（P〈0．01）。MSI的发生与MMR的表达存在相关性（P〈0．01）。MMR阳性细胞和阴性细胞共存在同一张切片内是MMR免疫组织化学的特点。结论 微卫星不稳定和错配修复基因异常可能参与部分喉鳞状细胞癌的发生,微卫星不稳定可能是喉鳞癌复发的特征性指标。     

Proteomic signatures in laryngeal squamous cell carcinoma

Laryngeal cancer remains a worldwide health problem. The identification of biomarkers unique to laryngeal cancer may provide new insights into its pathogenesis, as well as provide potential targets for novel therapies and early detection. In order to identify potential biomarkers, we performed a proteomic analysis of laryngeal cancer specimens. Using two-dimensional differential in-gel electrophoresis and mass spectroscopy, protein expression profiles from two laryngeal carcinoma specimens and corresponding adjacent normal tissue were analyzed. The results of our analysis showed that the expression of a number of proteins was significantly altered in the tumor specimens when compared to matched normal controls. The differentially expressed proteins were identified, and they included stratifin, S100 calcium-binding protein A9, p21-ARC, stathmin, and enolase. With these findings, we have identified potential biomarkers which may contribute to the pathogenesis of laryngeal carcinoma, and which may be suitable as targets for novel therapeutic and/or diagnostic modalities.     

端粒酶与喉癌相关性研究进展

端粒酶激活与恶性肿瘤发生发展之间存在着密切的关系。本文就端粒酶结构、功能及其与喉癌发生发展关系的最新研究进展作简要综述。     

喉鳞状细胞癌中脆性组氨酸三联体基因微卫星的不稳定性和杂合性丢失

目的　探讨脆性组氨酸三联体 (fragilehistidinetriad ,FHIT)基因微卫星不稳定性(microsatelliteinstability ,MSI)和杂合性丢失 (lossofheterozygosity ,LOH)与喉鳞状细胞癌 (简称鳞癌 )发生、发展的关系。方法　采用聚合酶链式反应 简单序列长度多态性 银染技术 ,分析 4 1例喉鳞癌中FHIT基因D3S12 34和D3S130 0位点的MSI及LOH。结果　D3S12 34位点LOH发生率为 4 4 4 % (16 /36 ) ,MSI发生率为 19 4 % (7/ 36 ) ;D3S130 0位点LOH发生率为 36 4 % (12 / 33) ,MSI发生率为 2 4 2 % (8/33)。两个位点总的LOH发生率为 5 2 6 % (2 0 / 38) ,总的MSI发生率为 2 8 9% (11/ 38)。总的LOH发生率与喉鳞癌患者TNM分期、病理分级、淋巴结转移及复发有关 (P <0 0 5 ) ,总MSI发生率与喉鳞癌患者淋巴结转移有关 (P <0 0 5 )。结论　FHIT基因LOH和MSI与喉鳞癌的发生、发展有关 ,并可能为喉鳞癌的早期诊断提供新的途径和依据     

基质金属蛋白酶MMP20与喉癌的浸润和转移

目的探讨基质金属蛋白酶MMP20与喉癌浸润和转移的关系.方法用RT-PCR和免疫组化的方法,研究MMP20在喉癌组织和其相邻的正常黏膜组织的差异表达量,分析其表达与喉癌浸润和转移的关系.数据分析借助SPSS10.0软件完成.结果 36例配对标本中MMP20基因在31例喉癌组织中的表达与其相应的正常黏膜组织差异表达不明显,而在5例喉癌组织中差异表达明显;MMP20蛋白绝大多数在癌巢细胞浆内表达（占93.2%,68/73）,少数主要在细胞核内表达（占6.8%,5/73）,MMP20蛋白在大多数喉癌组织中的表达明显高于其相应的正常黏膜组织;有淋巴结转移病例中,MMP20蛋白表达差异明显的病例数高于没有淋巴结转移者（P=0.023）;5例MMP20蛋白喉癌组织细胞核内表达中有4例与淋巴结转移有关.结论 MMP20蛋白在喉癌的淋巴结转移中起着重要的作用;MMP20蛋白的过度表达可作为喉癌淋巴结转移的标志.     

Eosinophilic infiltration in advanced laryngeal squamous cell carcinoma

Tumor-associated tissue eosinophilia (TATE) has been related to prognosis in epithelial cancers, including cancers at several head and neck sites. This study prospectively examined 248 patients with stage in and IV laryngeal squamous cell carcinoma to determine prevalence and potential prognostic significance of TATE. Pretreatment tumor specimens were histopathologically evaluated. Presence and degree of TATE were analyzed with regard to other tumor characteristics, patient characteristics, and outcome criteria. Median follow-up was 48 months. Eosinophilia was found in 22.5% of specimens and was not related to tumor site, stage, patient age or sex, or treatment modality. Overall and disease-free survival rates and response to induction chemotherapy did not differ significantly with respect to TATE. This study represents the first long-term, prospective evaluation of TATE and its prognostic significance in a single head and neck site. Contrary to the findings of earlier preliminary reports, our results suggest that TATE is not a clinical useful prognostic parameter in advanced laryngeal squamous cell carcinoma.     

喉癌前病变及喉鳞状细胞癌微卫星杂合性缺失的变化及其意义

目的:探讨喉癌前病变及喉鳞状细胞癌病变组织上杂合性缺失(LOH)的特征及其意义。方法:选取染色体3p、9p和17p上6个多态性微卫星位点D3S1234、D9S171、D9S1748、D9S162、INFA和p53,利用聚合酶链式反应-简单序列长度多态性-银染技术,对49例喉癌前病变和喉癌组织进行LOH分析。结果:6个微卫星标记物LOH发生率分别为:单纯过度增生3.70%,轻度不典型增生10.81%,重度不典型增生26.03%,喉鳞状细胞癌38.67%。其中LOH的总检出率在不同病理组间差异有统计学意义(χ2=17.686,P<0.01),其频率随病变程度加重而明显升高。6个多态性微卫星位点中,LOH发生率最高的位点D9S171(35.00%)。结论:基因水平的改变发生在喉癌变的早期阶段,微卫星标志物可能成为喉癌前病变早期诊断的有用标志物。     

Bcl-Xl protein expression in laryngeal squamous cell carcinoma

The Bcl-2 family of proteins regulate one of the steps in an evolutionary conserved apoptotic pathway. The long splice variant of Bcl-X (Bcl-Xl) is a potent antagonist of apoptosis. The aim of the study was to evaluate the relation between the presence of immunohistochemically detectable Bcl-Xl protein in laryngeal squamous cell carcinomas (LSCCs) and clinicopathological data, as well as DNA ploidy status and proliferative activity. In 50 specimens of LSCC, Bcl-Xl protein expression was evaluated immunohistochemically. Proliferative activity (SG2M-phase index) and DNA ploidy were measured by flow cytometry. In our study, Bcl-Xl protein expression decreased with decreasing tumour differentiation (P = 0.04). The majority of patients with Bcl-Xl protein immunoreactivity had no metastatic lymph node involvement (P = 0.01). Other factors such as age, gender, primary tumour size (pT) and type of cancer (keratinizing/non-keratinizing) were not associated with Bcl-Xl protein level. There was no correlation between Bcl-Xl protein and SG2M-phase index or DNA ploidy status. Our findings show that expression of Bcl-Xl protein is increased in a great fraction of laryngeal cancers. Further studies, however, are needed to clarify association between Bcl-Xl protein expression and clinical course of patients.     

Laser Doppler flux-metry in laryngeal squamous cell carcinoma

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Novel antiangiogenic therapy for solid tumours including laryngeal cancer is entering clinical trials. Quantifying microvessel density is considered the gold standard for measuring baseline angiogenesis and indeed 'the response to intervention'. We hypothesize that laser Doppler flux-metry could provide a non-invasive reliable method of quantifying blood flux within tumours. The aims were to determine whether a laser Doppler flux meter could be used as a reliable and reproducible method of estimating blood flux in the human larynx and to establish baseline Doppler flux recordings for the human larynx. The method used was a validation study in patients with laryngeal squamous cell cancer and normal controls. Statistical analysis was performed using SPSS software. We have demonstrated good reproducibility of laser Doppler measurements in human laryngeal mucosa (correlation coefficient 0.956 @P = 0.01). We have also derived arbitrary means of laser Doppler flux-metry in normal laryngeal mucosa and in squamous cell carcinoma of the larynx. Comparisons between normal and tumour laser Doppler flux-metry (LDF) readings showed no significant difference. We suggest that Laser Doppler flux-metry is a potentially useful tool with which to study blood flow in the larynx and propose arbitrary LDF levels for the normal and diseased human larynx.     

Hyponatremia associated with laryngeal squamous cell carcinoma

An association between laryngeal squamous cell carcinoma and inappropriate antidiuresis is described in a 76-year-old man. Even though all accepted diagnostic criteria for the syndrome of inappropriate secretion of antidiuretic hormone were fulfilled, abnormal levels of antidiuretic hormone were not demonstrated, leaving the mechanisms of this hyponatremia unclear.     

Langerhans cell related inflammatory reaction in laryngeal squamous cell carcinoma

The major cells involved in cancer cell kill are the T lymphocytes. However, T cells need to be activated upon antigen presentation, which is mediated by the antigen presenting cells, one of which is the Langerhans cell (LC). The purpose of this study was to assess the significance of LC and inflammatory cell infiltration in the laryngeal squamous cell carcinoma (LSCC). Forty-five patients who were operated on for LSCC between 1992 and 1999 were included in the study. The clinical and histopathological features of the patients were reviewed. A semiquantitative estimation of the lymphocyte dominant inflammatory reaction within and around the tumor was performed. Anti S-100 antibodies were used for immunohistochemical detection of LCs. Horseradish peroxidase method was used. LCs were present in almost all of the specimens within and around the tumor tissue. The S-100 results did not associate with grade, T and N stages, tumor stage, laryngeal site of involvement and survival (P>0.05). The S-100 results significantly associated with inflammatory reaction in the tumor tissue (P<0.01). In conclusion, the LC related response is not important to inhibit regional metastasis by cancer cells. The LC is not a reliable tool to determine prognosis of the patients with LSCC in the clinical practice.     

Jab1在喉鳞状细胞癌中的表达及临床意义

目的：探讨Jab1在喉鳞状细胞癌(LSCC)中的表达及其与LSCC临床病理和预后的关系。方法: 采用免疫组化SP法检测23例正常喉黏膜(NLT)和72例LSCC组织中Jab1的表达。结果: 在54.17%的LSCC中Jab1呈现过表达,并且与临床分期和淋巴结转移呈显著正相关,与患者的总生存率呈负相关(P<0.05)。结论: Jab1可能通过调节p27kip1蛋白的降解而参与LSCC的发生、发展, Jab1可以作为LSCC的一个预后指标。     

Expression of c-myc oncoprotein in laryngeal squamous cell carcinoma

Objective c-myc seems to play a pivotal role in normal growth and development as well in cellular transformation and carcinogenesis. Overexpression of the c-myc oncogene has been observed in many hematopoetic and solid tumors. The role of c-myc protein in squamous cell carcinoma of the head and neck in general and laryngeal squamous cell carcinomas (LSCCs) in particular is far from clear. The aim of this study was to evaluate the relations between the level of c-myc protein in LSCCs and the clinicopathological data of patients, DNA ploidy and the SG₂M phase index (PI).

Material and Methods The c-myc protein level was evaluated immunohistochemically in tumor specimens from 50 patients with LSCC. The DNA index and SG₂M PI were determined by means of flow cytometry.

Results We found c-myc protein in 34 (68%) tumors. Expression of c-myc protein was demonstrated to be frequent in non-metastatic cases (p=0.016). There was no association between c-myc protein level and age, primary tumor size, histological grading or type of cancer. In 13 (26%) cases we observed DNA aneuploid tumors. The mean value of the SG₂M PI was 22.5%. Expression of c-myc protein was not related to SG₂M PI or DNA ploidy.

Conclusions We have shown that c-myc oncoprotein may be involved in the genesis of LSCC. Our findings suggest that the detectability of c-myc protein is associated with a lower metastatic potential. The c-myc oncogene is probably not as important in laryngeal cancers compared to other cancers. Further investigations must be performed to establish the value of predicting nodal metastases in LSCC.     

Polo样激酶1在喉鳞状细胞癌中的表达及意义

目的 分析喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)中Polo样激酶1(polo like kinase 1,PLK1)蛋白的表达情况及其与临床因素的相关性.方法 用免疫组化SP法检测70例LSCC组织和21例癌旁组织中PLK1蛋白的表达情况,分析PLK1蛋白表达及与临...     

Expression of c-myc oncoprotein in laryngeal squamous cell carcinoma

OBJECTIVE: c-myc seems to play a pivotal role in normal growth and development as well in cellular transformation and carcinogenesis. Overexpression of the c-myc oncogene has been observed in many hematopoetic and solid tumors. The role of c-myc protein in squamous cell carcinoma of the head and neck in general and laryngeal squamous cell carcinomas (LSCCs) in particular is far from clear. The aim of this study was to evaluate the relations between the level of c-myc protein in LSCCs and the clinicopathological data of patients, DNA ploidy and the SG2M phase index (PI). MATERIAL AND METHODS: The c-myc protein level was evaluated immunohistochemically in tumor specimens from 50 patients with LSCC. The DNA index and SG2M PI were determined by means of flow cytometry. RESULTS: We found c-myc protein in 34 (68%) tumors. Expression of c-myc protein was demonstrated to be frequent in nonmetastatic cases (p = 0.016). There was no association between c-myc protein level and age, primary tumor size, histological grading or type of cancer. In 13 (26%) cases we observed DNA aneuploid tumors. The mean value of the SG2M PI was 22.5%. Expression of c-myc protein was not related to SG2M PI or DNA ploidy. CONCLUSIONS: We have shown that c-myc oncoprotein may be involved in the genesis of LSCC. Our findings suggest that the detectability of c-myc protein is associated with a lower metastatic potential. The c-myc oncogene is probably not as important in laryngeal cancers compared to other cancers. Further investigations must be performed to establish the value of predicting nodal metastases in LSCC.     

在喉鳞状细胞癌中的表达

目的:研究癌基因STK15在喉鳞状细胞癌中的表达，探讨STK15与喉鳞状细胞癌的相关性。方法：应用SP免疫组织化学法检测40例喉鳞状细胞癌及30例声带息肉中STK15的蛋白表达。结果：STK15在喉鳞状细胞癌和声带息肉中的阳性率分别为67.5%（27/40）、33.3%（10/30），二者之间差异有统计学意义（P＜0.05）。STK15蛋白表达与喉鳞状细胞癌的TNM分期及淋巴结转移有关（P＜0.05），与喉鳞状细胞癌病理学分级、原发部位及患者的性别、年龄无关（P＞0.05）,且STK15蛋白阳性表达强度与喉鳞癌患者的TNM分期有关（P＜0.05）。结论：STK15在喉鳞状细胞癌的发生、发展中起重要作用，可能成为喉鳞状细胞癌基因治疗的新靶点。     

喉癌E－钙粘附素蛋白表达

目的探讨上皮钙粘附索蛋白表达与喉鳞状细胞癌的临床和病理特征关系。方法应用免疫组化SP法检测60例喉癌中上皮钙粘附素(E—cad)蛋白表达情况,并将其表达与喉癌临床分型、临床分期、病理分化程度及颈淋巴结转移情况作统计学分析。结果E-cad蛋白在喉癌中表达下降,其表达与喉癌的临床分期、病理分化程度以及颈部淋巴结转移有关,与肿瘤原发部位无关。结论E-cad异常表达在喉癌的发生发展特别是颈淋巴结转移中发挥了重要作用,可作为判断喉癌恶性程度和淋巴结转移的一个生物学指标。