声门上型喉癌中端粒酶活性的检测及其意义

目的：探讨端粒酶活性在声门上型喉癌中的表达及其意义。方法：采用端粒重复序列扩增法检测了ＨＥＰ－２喉癌细胞系,２６例声门上型喉癌组织和１５例癌旁组织。结果：ＨＥＰ－２喉癌细胞系呈端粒酶阳性,癌组织的端粒酶阳性率为８４．６％,明显高于癌旁组织的阳性率４０％（Ｐ〈０．０１）,喉癌组织端粒酶活性的表达与临床分期和有无颈淋巴结转移未出现出相关性（Ｐ〉０．０５）。结论：端粒酶活化是喉癌发生的重要遗传学改变,但     

头颈部鳞癌端粒酶活性的定量检测

目的：了解头颈部鳞癌及其颈淋巴结转移癌端粒酶的表达情况,探讨粒酶活性定量分析在头颈鳞癌诊断中的价值。方法：采用端粒重复序列液体闪烁计数法检测端粒酶活性。共检测取自２５例头颈部鳞癌患者的组织样本５５份,其中７例患者同时取有原发癌及其颈淋巴结转移癌两份样本,以２３份正常组织为对照。结果：①３２份原发鳞癌组织中端粒酶活性（ｃｐｍ值）在１０００以上的２８份,除２份外,均明显高于正常组织;２３份正常组织的端     

喉鳞状细胞癌与端粒酶亚单位表达

目的 检测喉鳞状细胞癌（简称喉鳞癌）相关组织中端粒酶亚单位（端粒酶逆转录酶、端粒酶相关蛋白1和端粒酶RNA组分hTR）mRNA的表达,研究不同的端粒酶亚单位的表达与喉鳞癌发生的关系。方法 对34例喉鳞癌病例,采用逆转录聚合酶链（RT-PCR）技术检测上述三种端粒酶亚单位在喉癌组织、对应的癌旁组织和转移淋巴结中的mRNA表达。结果 喉癌组织、对应癌旁组织和转移淋巴结中端粒酶逆转录酶mRNA的阳性率分别为88．2％（30／34）、5．9％（2／34）和90．0％（9／10）,三种组织的阳性率间存在显著性差异（P〈0．05）,喉癌组织和转移淋巴结组织的阳性率显著高于癌旁组织（P〈0．05）。端粒酶相关蛋白1和端粒酶RNA组分mRNA在喉癌组织、对应癌旁组织和转移淋巴结中的阳性率均为100％。结论 本研究结果提示端粒酶依赖途径是喉鳞癌发生的方式之一。与端粒酶相关蛋白1和端粒酶RNA组分比较,端粒酶逆转录酶表达的上调在端粒酶依赖途径的喉鳞癌的发生中占有更重要的地位。     

喉癌标本端粒酶活性的检测

目的：探讨端粒酶生在喉癌发生过程中的作用。方法：采用ＴＲＡＰ方法检测３４例头颈肿瘤组织标本中的端粒酶活性。结果：在２７例喉癌患者中有２３例同端粒是笥，阳性率８５．２％，２７例相应癌旁组织有７例检出端粒酶阳性，阳性率２５．９％，７例喉乳头瘤瘤患者中有３例检出，阳性率４２．９％，结论：端粒酶活化并非只发生在喉癌进展的晚期阶段，在肿瘤形成的早期也有一定程度的端粒酶激活。端粒酶活性可能民癌的恶性程度有关。     

喉癌和癌旁组织的端粒酶活性检测

目的：探索端粒酶活性与喉癌发生发展的关系。方法：采用重复序列扩增法（TRAP－PCR）检测56例手术切除的喉癌组织和癌旁粘膜组织的端粒酶活性。喉癌组织均经病理证实,喉癌旁粘膜组织中有正常喉粘膜41例,轻度不典型增生15例。结果：喉癌组织端粒酶活性阳性率为91．07％（51／56）,正常喉粘膜和轻度不典型增生喉粘膜的阳性率分别为9．76％（4／41）和33．33％（5／15）,喉癌组织和癌旁粘膜组织中端粒酶活性阳性率有显著差异（P<0．01）。癌旁上皮端粒酶活性阳性的9例患者其喉癌组织端粒酶活性皆为阳性。结论：端粒酶激活与喉癌的发生发展有密切关系,并可作为喉癌分子诊断的肿瘤标记物。     

鼻咽癌病人端粒酶表达的研究

目的：研究端粒酶（ＴＬＭＡ）在鼻咽癌（ＮＰＣ）中的表达。方法：采用ＴＲＡＰ ＰＣＲ ＥＬＩＳＡ法探讨１８例ＮＰＣ，２例放疗后ＮＰＣ，４例癌旁组织及４例慢性鼻咽炎鼻咽部活检组织中ＴＬＭＡ表达。结果：１８例ＮＰＣ ＴＬＭＡ阳性率为８８．９％。４例癌旁组织阳性率为７５．０％，慢性鼻咽炎全部为阴性。１例复发性ＮＰＣ为阳性，１例疗后未复发为阴性。ＴＬＭＡ表达与ＮＰＣ分期、颈淋巴结转移似无明显关系。结论：ＴＬ     

喉癌和癌旁组织的端粒酶活性检测

目的：探索端粒酶活性与喉癌发生发展的关系。方法：采用重复序列扩增法（ＴＲＡＰ－ＰＣＲ）检测５６例手术切除的喉癌组织和癌旁粘膜组织的端粒酶活性。喉癌组织均经病理证实,喉癌旁粘膜组织中有正常喉粘膜４１例,轻度不典型增生１５例。结果：喉癌组织端粒酶活性率为９１．０７％（５１／５６）,正常喉粘膜和轻度不典型增生喉粘膜的阳性率分别为９．７６％（４／４１）和３３．３３％（５／１５）,喉癌组织和癌旁粘膜组织中端     

CD44s及CD44v 6在喉鳞癌组织中的表达

目的：探讨标准型ＣＤ４４（ＣＤ４４ｓ）及变异型ＣＤ４４（ＣＤ４４ｖ６）在喉鳞癌的表达与临床病理特征的关系,及其在喉鳞癌发生发展中的作用。方法：应用免疫组化ＳＰ法检测４６例喉鳞癌及２０例癌旁正常组织中ＣＤ４４ｓ和ＣＤ４４ｖ６的表达情况。结果：ＣＤ４４ｓ在喉鳞癌淋巴结转移者（９４．４％）及Ｔ３－４者（９６．２％）的表达水平,较无淋巴结转移者（６７．９％）及Ｔ１－２者（５５．０％）高;ＣＤ４４ｖ６在喉鳞     

人类鼻咽癌端粒酶活性的研究及其临床意义

目的 探讨端粒酶在鼻咽癌中的表达及其临床意义。方法 采用ＴＲＡＲ－银染法对４２例鼻咽部低分化鳞状细胞癌、１０例鼻咽部正常粘膜和８例鼻咽纤维血管瘤进行端粒酶活性检测及血清ＶＣＡ／ＩｇＡ检测,并分析其与临床病理的关系。结果 鼻咽部正常粘膜和鼻咽癌端粒酶阳性率分别为２０％和８８．１％,８例鼻咽纤维血管瘤均未检测到端粒酶活性。鼻咽癌伴颈部淋巴结转移者端粒酶阳性率高于无颈部淋巴结转移者（Ｐ＝０．０３５）,临     

头颈部恶性肿瘤组织中端粒酶活性定量检测及其意义

目的：探讨头颈部恶性肿瘤组织中端粒酶活性水平及其与肿瘤发生、发展的关系。方法：用改进的PCR—TRAP法对36例头颈部肿瘤组织、正常组织、癌旁组织分别进行端粒酶活性定量检测。结果：36例头颈部恶性肿瘤中有32例(88．9％)阳性表达，癌旁组织有4例(11．1％)阳性表达，正常组织有l例(2．8％)阳性表达，肿瘤组织与癌旁组织和正常组织之间，差异有显著性意义(P＜0．05)。端粒酶活性水平与临床分期、病理类型和分化程度不呈线性相关，癌旁组织和正常组织阳性病例的端粒酶定量水平较肿瘤组织低。结论：端粒酶的激活与头颈部恶性肿瘤的发生、发展可能密切相关；端粒酶活性有可能成为恶性肿瘤分子诊断的标志物和治疗的新靶点。     

Quantitative assay of telomerase activity in head and neck squamous cell carcinoma and other tissues

OBJECTIVES: To confirm the applicability and use of a new technique to detect and quantify telomerase activity of specimens from head and neck malignant neoplasms and to explore whether the levels of telomerase activity can be a useful marker for cancer risk assessment in head and neck malignant neoplasms. DESIGN: Ninety-six specimens from 39 patients with head and neck malignant neoplasms were obtained. The specimens included 39 from patients with primary tumors (25 with head and neck squamous cell carcinoma and 14 with others), 10 from patients with neck metastases, 10 from patients with dysplasias, and 37 from patients with normal tissue. HeLa cell lines were used as positive control samples. MAIN OUTCOME MEASURE: The levels of telomerase activity were determined using a liquid scintillation counter. RESULTS: The new method has a high rate of outcome reproducibility. The intrabatch and extrabatch variations were 15.6% and 16.4%, respectively. The linear relationship was good between the telomerase activity and the value within 700 radioactive cpm (rcpm) to approximately 7000 rcpm. The levels of telomerase activity determined by radioactive count were more than 1000 rcpm in 42 of the 49 malignant specimens and much more than that in the normal tissues, with the exception of 3 specimens. The levels of telomerase activity in normal tissues were less than 1000 rcpm in every sample and less than that in the malignant neoplasm samples, with the exception of 1 specimen (P < .000). Higher levels of telomerase activity in 2 of 10 tissues from patients who had dysplasias were detected (2 specimens from patients who had severe dysplasia). The differences in the levels of telomerase activity between the head and neck squamous cell carcinomas and the other tumors were not statistically significant (P > .05). CONCLUSIONS: Detection of telomerase activity in head and neck malignant neoplasms can be a useful marker for the assessment of cancer. Telomerase reactivation may play an important role in tumorigenesis in head and neck squamous cell carcinoma. The quantification of telomerase activity may have clinical diagnostic value for head and neck malignant neoplasms.     

Reactivation of telomerase in squamous epithelial carcinomas in the area of the head and neck

BACKGROUND: Head and neck cancer development involves the accumulation of multiple cellular alterations over a long period of time. Selection and expansion of altered cell clones can lead to the evolution of a malignant phenotype. The theory of carcinogenesis suggests that unlimited cell proliferation is required for development of malignant disease and cancer must attain immortality for progression to malignant states. One step in the immortalization process may be the reactivation of telomerase. This enzyme complex can prevent the continuous shortening of telomeres which is observed at each cell cycle. RESULTS: Telomerase activity was detected in 68% of squamous cell carcinomas of pharynx and larynx and 58% of histologically tumor-free resection margins. Recurrences occurred with a higher rate in cases with telomerase positive primary tumor. The importance of telomerase activity in histologically negative resection margins needs further investigations. Telomerase activity was found in 90% of corresponding lymph nodes without any correlation to metastasis in the lymph node. CONCLUSIONS: The reactivation of telomerase seems to be an important step in carcinogenesis of head and neck cancers. Further studies are necessary in order to understand the role of the enzyme as a possible marker for tumor progression and clinical outcome.     

Sentinel Lymph Node Radiolocalization in Head and Neck Squamous Cell Carcinoma

Objectives: To determine the feasibility of sentinel node radiolocalization in stage N0 in head and neck squamous cell carcinoma and to gain insight as to whether the sentinel node could be prognostic of regional micrometastatic disease. Study Design: A prospective report on the application sentinel node radiolocalization in eight patients with N0 squamous cell carcinoma of the head and neck region. Methods: For each patient a peritumoral submucosal injection of filtered technetium (^99mTc) prepared with sulfur colloid was performed immediately following intubation. After at least 30 minutes, focal areas of accumulation corresponding to a sentinel node were marked on the skin surface. Complete neck dissections were performed, and the sentinel nodes were identified for later histological evaluation and comparison to the remaining lymphadenectomy specimen. Results: Sentinel node radiolocalization accurately identified two or more sentinel lymph nodes in all eight cases. In one patient, two of the three lymph nodes containing micrometastatic disease were sentinel lymph nodes. There was no instance in which sentinel node was negative for micrometastatic disease while being positive in a nonsentinel lymph node. Conclusions: Accurate localization of the sentinel lymph node using radiolabeled sulfur‐colloid is feasible in patients with squamous cell carcinoma of the head and neck region. Although sentinel node radiolocalization in head and neck squamous cell cancer may potentially reduce the time, cost, and morbidity of regional lymph node management, more experience with technique is required before its role can be determined.     

Impact of positron emission tomography on the initial staging and therapy in locoregional advanced squamous cell carcinoma of the head and neck

OBJECTIVE: To evaluate the impact of 18F-fluoro-deoxy-glucose positron emission tomography after standard diagnostic workup in patients with advanced head and neck squamous cell carcinoma on staging and radiation treatment planning. STUDY DESIGN: Prospective controlled study. METHODS: Forty-eight patients (42 men and 6 women; mean age, 61 y; age range, 35-85 y) with histologically confirmed, advanced-stage (any T, N> or =N2 or T> or =T3, any N) mucosal head and neck squamous cell carcinoma underwent positron emission tomography. The routine workup consisting of physical examination, panendoscopy, chest x-ray film, and contrast-enhanced high-resolution helical computed tomography scan (HRCT) was used for comparison. End points were the extent of lymph node disease, distant metastases, and second primary tumors. RESULTS: In 41 of 48 patients (85%) the lymph node findings between HRCT and positron emission tomography were concordant. In three patients positron emission tomography led to an upstaging of the tumor in its N category, and in four patients positron emission tomography underestimated lymph node involvement. Positron emission tomography revealed more difficulties in delineating lymph node metastases adjacent to the primary tumor than did HRCT, but was superior for the detection of distant and contralateral lymph node metastases. Positron emission tomography suggested distant metastatic lesions in 6 of 48 patients (13%). Cytological workup confirmed distant metastases in two (4%) and second primary tumors in another two patients (4%). Positron emission tomography results were false-positive in two (4%) patients because of inflammatory changes. CONCLUSIONS: Whole-body PET is able to assess lymph node involvement, distant metastases, and second primaries in a single study. Even after a routine clinical staging, positron emission tomography leads to a change of treatment in approximately 8% of patients.     

喉癌端粒酶活性检测及其与颈淋巴结转移的相关性

目的 :探讨喉鳞状细胞癌端粒酶活性表达及其与颈淋巴结转移的相关性。方法 :采用多聚酶链反应 -酶联免疫吸附法 (PCR- EL ISA) ,对 47例喉鳞状细胞癌组织及 10例声带炎性息肉组织的端粒酶活性进行定量检测。结果 :47例喉鳞癌组织中 39例端粒酶呈阳性 (83% ) ,而 10例声带炎性息肉组织均为阴性 ,两组差异有极显著性意义 (P <0 .0 1) ;端粒酶活性在伴有颈淋巴结转移的喉癌中显著高于无淋巴结转移者 (P <0 .0 5 )。结论 :端粒酶在喉癌组织中有较高的表达 ,可作为喉癌的肿瘤标志物。喉癌组织端粒酶活性有可能作为预测喉癌转移和预后的指标 ,并可望指导临床有针对性地应用选择性颈廓清术。     

Simultaneous bilateral neck dissections

From April 1985 to December 1989, 65 patients with advanced head and neck squamous cell carcinoma, underwent simultaneous bilateral neck dissection (SBND) at Saitama Cancer Center. Three and five year survival percentages were 53 and 42%, respectively. In patients without histologic involvement of cervical nodes, five year survival rate was 83%, whereas in those with nodal involvement five year survival fell to 32% (p less than 0.005). The conclusion were the following: (1) Of 38 patients diagnosed to have lymph node involvements on one side of neck before operation, 8 patients (22%) were found to have bilateral lymph node metastasis in clinicopathological study. Of 13 patients having no clinical lymph node metastasis on both sides of neck, 7 patients (54%) were found to have unilateral lymph node metastasis. Of 16 patients diagnosed to have bilateral lymph nodes involvement, 10 patients were found to have bilateral neck metastasis and 2 had unilateral neck metastasis. (2) Of 35 cases of hypopharyngeal canners, 19 cases had clinically positive lymph nodes on one side of neck. Of these 19 cases, 5 cases (26%) had histologically positive nodes on the opposite side. 14 (40%) of 35 cases had metastasis on the opposite side. In conclusion, SBND is a proper treatment for metastatic cervical cancer from a primary lesion of the head and neck, especially in hypopharyngeal cancers, because the rate of recurrence seems to be related more to the difficulty in controlling lymph node metastasis than to the failure in treatment of the primary cancer.     

Telomerase Activity Is Upregulated in Laryngeal Squamous Cell Carcinoma

Objective/Hypothesis The immortalizing enzyme telomerase has been linked to carcinogenesis and is being targeted as a novel molecular marker. This study investigated telomerase expression in patients with laryngeal squamous cell carcinoma and correlated telomerase activity with conventional prognostic parameters. Study Design A consecutive series of patients with laryngeal squamous cell carcinoma undergoing surgical salvage for persistent or progressive disease after failed radiation therapy. Methods Twenty patient samples of laryngeal squamous cell carcinoma and 20 adjacent histologically normal mucosal samples were assayed using the telomeric repeat amplification protocol (TRAP) method for detection of telomerase activity. The leukemic cell line, K562, acted as a positive control and the human fibroblast line, Hs21Fs, as a negative control. A sample was classified as telomerase positive when an RNase‐sensitive hexameric repeat ladder was observed. Absence of laddering was considered a negative result. Results Seventeen of 20 (85%) tumor samples and 4 of 20 (20%) adjacent histologically normal samples were telomerase positive. No statistically significant difference was observed when densitometric readings were compared by T category, tumor grade, or site (by ANOVA). Conclusions Although telomerase activity is present in laryngeal cancer, levels of activation do not correlate with conventional parameters used for prognostication. Our study indicates that the marker may be a useful adjunctive method in the diagnosis of malignancy after radiation failure.