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     

头颈部鳞癌及癌旁组织端粒酶活性检测

目的：研究原发头颈部鳞癌及相关癌旁组织中端粒酶活性表达,探讨春作为头颈部鳞癌分子生物学标志物的可能性。方法：采用ＴＲＡＰ－ＰＣＲ－ＥＬＩＳＡ,对３２例原发头颈部鳞癌及１５例癌旁组织进行端粒酶活性检测。结果：３２例原发头颈部鳞癌中,２７例端粒酶活化,阳性率为８４．４％;１５例癌旁组织中５例端粒酶活化,阳性率为３３．３％。有淋巴结累及者端粒酶阳性率（８６．７％）高于无淋巴结累及者（８２．４％）,低分化     

头颈鳞癌组织和细胞系中免疫球蛋白M表达的初步研究

目的 明确头颈鳞癌组织及传代细胞系中免疫球蛋白M(IgM)的表达情况.方法 采用免疫组化染色(SABC法)检测头颈鳞癌组织及阴性对照组织中IgM蛋白的表达情况,比较分析IgM在头颈鳞癌与对照组织间的表达差异;采用Western Blot、流式细胞仪间接免疫荧光法检测IgM在头颈鳞癌细胞系中的表达情况.结果 IgM在头颈鳞癌及阴性对照组织中的阳性表达率分别为68.6％和24.5％,差异具有统计学意义(P＜0.05).随着鳞状上皮及鳞癌细胞分化程度的降低,IgM的表达部位有从细胞膜向细胞浆转变的趋势(P＜0.05);头颈鳞癌细胞裂解液中存在与人IgMμ链分子量一致(75KD)且能与抗人IgMμ链抗体发生特异性反应的蛋白; 4种头颈鳞癌细胞系中IgM平均免疫荧光强度为9.25±0.82％ (CNE-1),8.76±0.54％ (Tca8113),13.72±1.73％ (Hep-2)和12.1±1.19％ (HNE-1),与阴性对照组1.87±0.24％比较,差异均具有统计学意义(P＜0.05).结论 头颈鳞癌组织和传代细胞系中存在IgM蛋白的表达,且IgM表达部位与鳞状上皮细胞的分化程度有关,但IgM在头颈鳞癌表达的临床意义、生物学作用和机制等尚有待进一步探讨和研究.     

Topoisomerase I activity in squamous cell carcinoma of the head and neck

In recent preclinical and clinical trials, topoisomerase I inhibitors have shown great promise as antitumor agents. These agents are most effective against tumors with high topoisomerase I activity. Therefore, determining topoisomerase I activity in advance may predict response to topoisomerase I inhibitors. Squamous cell carcinoma of the head and neck and normal tissue samples were obtained from 12 patients. Cellular extracts were prepared, and topoisomerase I activity assays were performed. The results suggest that topoisomerase I activity in squamous cell carcinoma of the head and neck is increased approximately sixtyfold compared to normal tissue. Increased activity often correlates with clinical responsiveness; these results predict that topoisomerase I inhibitors should be effective and selective against squamous cell carcinoma of the head and neck.     

Angiogenesis in head and neck 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. Research into this process not only offers new insights into tumour biology but is also leading to the development of realistic novel and minimally toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines and pathways have been characterized and their interrelationships are becoming increasingly complex as new findings are made. This article reviews the current understanding of tumour angiogenesis, the basic mechanisms involved and the more important and investigated pathways and proteins involved.     

Hyercalcaemia in head and neck squamous cell carcinoma

PURPOSE OF REVIEW: Patients with advanced head and neck cancer are being treated with chemo-radiotherapy, and life is being prolonged, with or without persistent disease, for longer than was previously. Hypercalcaemia may present in patients with advanced or disseminated head and neck cancer, and, as such, these patients may present to a larger variety of clinicians for advice concerning their symptoms and illness. Modes of presentation of hypercalcaemia and treatment strategies are reviewed. RECENT FINDINGS: There were previously few large series of head and neck cancer patients diagnosed with hypercalcaemia, which may or may not have been related to their cancer being treated. Investigations, by way of blood/serum calcium level, may identify such patients. Patients with cancer-related hypercalcaemia have a poor prognosis, but many may respond temporarily to treatment when offered, with an improvement of their quality of life and death. SUMMARY: Hypercalcaemia should and must be considered in all patients who have or possibly have a diagnosis of a head and neck cancer and who present unwell with symptoms of fatigue, lethargy and somnolence. Investigation must include serum calcium (corrected for serum albumin binding) and parathyroid hormone level. Patients may be treated by a combination of rehydration and bisulphonate therapy until the serum calcium is reduced to a level below 3 mmol/l. The majority of patients diagnosed with hypercalcaemia due to head and neck malignancy die of their diseases in the short term, but some may enjoy a prolongation of life with reasonable quality if diagnosed and treated aggressively.     

Inhibition of caspase-9 activity in cisplatin-resistant head and neck squamous cell carcinoma

We have previously reported that cisplatin induces caspase-9 activation in head and neck squamous cell carcinoma cells (HNSCCs) in vitro, and the use of a specific inhibitor of caspase-9 blocks cisplatin-induced apoptosis in HNSCCs. Our purpose here was to determine whether HNSCCs selected for resistance to cisplatin fail to exhibit caspase-9 activation in response to cisplatin. Cisplatin-resistant HNSCCs (CRHNSCCs) were selected for growth in the presence of cisplatin. Following cisplatin treatment, no protelyzed caspase-9 subunits were detected in the CRHNSCCs, whereas proteolytic degradation of procaspase-9 was observed in parental cisplatin-sensitive HNSCCs (CSHNSCCs). Using a direct enzymatic assay measuring cleavage of the synthetic peptide substrate (LEHD-AFC), caspase-9 activity in cisplatin-treated CRHNSCCs was less than that in cisplatin-treated CSHNSCCs. Because caspase-9 activation requires the release of mitochondorial cytochrome c (Cyt c) into the cytoplasm, we determined the level of cytoplasmic Cyt c in response to cisplatin treatment. Interestingly, following cisplatin treatment, the same extent of increase in cytoplasmic Cyt c was evident and the expression of Bcl-2 family proteins (Bcl-2 and Bcl-XL) remained unchanged in both CRHNSCCs and CSHNSCCs. These results suggest that in certain HNSCC cell types, inhibition of caspase-9 activity represents another mechanism of acquired cisplatin resistance. This inhibition mechanism may be independent of the release of Cyt c into the cytoplasm.     

Papillary squamous cell carcinoma versus verrucous squamous cell carcinoma of the head and neck

Papillary squamous cell carcinoma and verrucous squamous cell carcinoma of the head and neck may be confused. The clinicopathological profile of the two neoplasms is presented and the differential diagnosis is discussed. A correct diagnosis is imperative in order to institute the most appropriate treatment.     

Integrins in head and neck squamous cell carcinoma invasion

OBJECTIVE: To relate the invasive properties of different squamous cell cancer cell lines to the function and expression of the integrins. STUDY DESIGN: A series of in vitro and in vivo experiments were designed to assess and compare integrin expression and function in two different head and neck squamous cell carcinoma cell lines. METHODS: Invasive properties of two squamous cell carcinoma cell lines (UM-SCC-1 and JHU-022-SCC) were assessed using an in vitro artificial matrix assay as well as an in vivo system with orthotopically implanted tumor cells in mice. Whole cell and surface expression levels of integrin subunits (alpha2, alpha3, alpha5, alpha6, beta1, and beta4) were determined for each cell line using Western blot analysis and flow cytometry. We compared the ability of JHU-022-SCC and UM-SCC-1 cells to bind the extracellular matrix elements collagen IV, fibronectin, laminin 5, and laminin10 using an in vitro adhesion assay. Contributions of the different integrins to the adhesive properties were determined by selective antibody blocking of different subunits. RESULTS: The UM-SCC-1 cell line is 50% more invasive in vitro and displays a greater propensity for perineural and lymphatic invasion in vivo. The UM-SCC-1 cells exhibited greater adherence to fibronectin than JHU-022-SCC cells. Alpha6 and beta4 expression is approximately twofold greater in the JHU-022-SCC cells. Alpha2, alpha3, and beta1 expression appears to be upregulated in UM-SCC-1 cells. CONCLUSION: The UM-SCC-1 carcinoma cells are more invasive than JHU-022-SCC cells and may be related to differential expression of the integrins alpha6beta4, alpha3beta1, and alpha2beta1.     

Mononuclear phagocytes in head and neck squamous cell carcinoma

The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production.     

c-myc与c-neu癌基因在头颈部鳞状上皮癌旁组织及癌变中的表达及相互关系

用免疫组织化学定量方法观察在上皮癌变过程中c－myc及c－neu的表达及二者的相互关系及意义。标本取自病人喉部及颊粘膜，包括癌旁正常上皮（EAC）（N，14例）、慢性炎症（IF，12例）、鳞状细胞癌（SCC，30例）。一抗分别为抗c－neu及c－myc单抗。采用网格测试法对myc阳性反应细胞计数，可得出上皮不同层次myc的阳性指数；用图象分析法对neu的阳性反应定量，可得出包括阳性反应面积和反应程度的neu阳性指数neuPI。结果显示myc和neu在头颈部上皮癌变过程中都有较高的表达，从N、IF、EAC到SCC组，有逐渐增大的趋势，其表达程度主要与肿瘤细胞的分化关系密切，在SCC组中基本以分化好的SCC表达最高，c－myc在上皮癌变中的表达与neu的表达高度相关。此外发现，myc在上皮棘层细胞的表达更能反映病变的状态。     

Molecular pathogenesis of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) represents 6% of all cancers. The overall 5-year survival rate for patients with this type of cancer is among the lowest of the major cancer types and has not improved dramatically during the last decade. The pathological staging, in particular the nodal stage, is the most important factor in HNSCC. The lack of progress in head and neck oncology emphasizes the importance of molecular genetic studies to define alterations that may correlate with tumor behavior. The molecular alterations observed in HNSCC are mainly due to oncogene activation and tumor suppressor gene inactivation, leading to deregulation of cell proliferation. These alterations include gene amplification and overexpression of oncogenes such as ras, myc, EGFR and cyclin D1, and mutations and deletions leading to p16 and TP53 tumor suppressor genes inactivation. This article reviews the molecular changes commonly observed in HNSCC. The biological function of these markers and the potential clinical application are discussed. Advances in the understanding of the molecular basis of HNSCC will help in the identification of new molecular markers that could be used for a more accurate diagnosis and assessment of prognosis and may open the way for novel approaches to treatment and prevention.     

Basaloid squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.     

Proteolytic patterns of head and neck squamous cell carcinoma

The significance of plasminogen activators and matrix metalloproteases for clinical outcome, growth and metastatic behavior of head and neck squamous cell carcinoma (SCC) is still controversial. The majority of studies has been based on either immunohistological stainings, which provide only limited quantitative information, or in vitro experiments. We analyzed 44 head and neck SCC and 11 mucosa tissue samples for the expression of gelatinolytic or fibrinolytic proteases by quantitative zymographic analysis and compared lytic activities to clinical and histopathological data. We calculated activation ratios for matrix metalloproteinases-2 and –9 (MMP-2 and MMP-9) by separate evaluations of inactive and activated MMP forms. Increased gelatinolytic and fibrinolytic activity was found in head and neck SCC when compared to mucosa. Increased values were caused by MMP-9 and urokinase type plasminogen activator, respectively. No statistically significant correlations of either protease lytic activity or activation ratio could be related to T-stage, metastasis, tissue necrosis or the differentiation stage of tumors. The data recorded are compared with previously published reports. Received: 27 August 1998 / Accepted: 6 January 1999     

Basaloid squamous cell carcinoma of the head and neck

PURPOSE OF REVIEW: Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma and was first described as a distinct entity in 1986. Basaloid squamous cell carcinoma seems to have a poorer survival rate than classical squamous cell carcinoma. On the basis of a critical literature survey, we attempt to evaluate if basaloid squamous cell carcinoma is really more aggressive and presents a poorer outcome than squamous cell carcinoma. RECENT FINDINGS: All papers are retrospective, and most include small numbers of cases, which are further diminished when subdivided according to specific sites. Only in three studies was basaloid squamous cell carcinoma of the head and neck region compared with matched squamous cell carcinoma controls. These studies did not show a uniform tendency regarding the aggressiveness and outcome of basaloid squamous cell carcinoma. In addition, several recent papers confirmed the presumed greater aggressiveness and worse outcome, and other recent papers questioned these characteristics. SUMMARY: The presented literature survey does not permit conclusions regarding the aggressiveness and outcome of basaloid squamous cell carcinoma compared with squamous cell carcinoma. Greater numbers of basaloid squamous cell carcinoma should be studied and compared with site-matched, stage-matched, and age-matched controls of conventional squamous cell carcinoma.     

Proliferative activity following induction chemotherapy in squamous cell carcinoma of the head and neck

Summary Forty-six patients with advanced head and neck squamous cell carcinomas received two courses of chemotherapy with cisplatinum and bleomycin before undergoing cancer surgery. After surgery, histological serial sections of the resection specimens were examined. Biopsies from each resected specimen were shock-frozen for immunohistochemical examinations using the monoclonal antibodies Ki-67 and RPN-511, which are associated with cell proliferation. In no case did the morphologic analysis demonstrate complete tumor regression after chemotherapy. Thirty-seven patients showed partial tumor regressions histologically, as seen by tumor shrinkage of more than 50%. Nine of the specimens showed only minor regressions, with shrinkage less than 50%. The immunostaining of the frozen sections revealed in all cases the expressions of the Ki-67 nuclear antigen and the presence of specific transferrin (RPN-511) receptors in the proliferative compartments of the carcinomas.Presented at the annual meeting of the Austrian Society of Otorhinolaryngology-Head and Neck Surgery (Österreichische Gesellschaft für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie), 14–18 September 1988, Feldkirch, Austria Offprint requests to: R. Bettinger