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.     

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.     

人乳头状瘤病毒及pRb在头颈鳞状细胞癌中的表达

目的：探讨人乳头状瘤病毒(HPV)和视网膜母细胞瘤蛋白(pRb)在头颈鳞状细胞癌中的表达及其临床意义。方法：对首选手术治疗的73例头颈鳞状细胞癌患者，用GP5( )bioGP6( )介导的酶联吸附免疫PCR和type-specific PCR检测HPV；免疫组织化学法检测pRb在肿瘤组织中的表达。结果：HPV DNA在73例肿瘤组织中的阳性率为12．3％，均为HPV 16 DNA；口咽癌患者HPV阳性率为18．0％，口腔癌患者HPV阳性率为7．5％。pRb在73例肿瘤组织中的阴性率为12．3％。结论：尽管HPV阳性肿瘤临床多为进展期，常伴有颈淋巴结转移，但HPV阳性患者预后较阴性患者为好．提示HPV阳性、pRb阴性的头颈鳞状细胞癌对放疗反应敏感．     

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.     

The association between elevated EphB4 expression, smoking status, and advanced-stage disease in patients with head and neck squamous cell carcinoma

OBJECTIVE: To examine the expression of EphB4 in tumor tissue, surrounding normal tissue, and metastatic lymph node in patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate its association with disease stage and smoking. DESIGN: A retrospective study. SETTING: University of Southern California-University Hospital, University of Southern California and Los Angeles County Medical Center, and Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles. PATIENTS: Forty-eight patients with different stages of HNSCC (I-IV) were enrolled into this study. Staging was based on the staging system of the American Joint Committee on Cancer. MAIN OUTCOME MEASURES: EphB4 expression in tumor tissue, surrounding normal tissue, and metastatic lymph node was evaluated by immunohistochemical analysis, Western blot, and real-time polymerase chain reaction. EphB4 expression was then compared between patients based on disease stage and smoking status. RESULTS: EphB4 expression was detected in all tumor specimens and metastatic lymph nodes of patients with HNSCC, but expression levels were higher in the metastatic lymph nodes. There was a statistically significantly higher mean EphB4 protein expression and EphB4 gene amplification in patients with advanced disease (stage III or IV) vs patients with initial disease (stage I or II) and in smokers vs nonsmokers. CONCLUSIONS: Overexpression of EphB4 is associated with advanced stages of HNSCC as well as with patients who smoke. These data are the first to demonstrate the association of EphB4 with advanced stages of disease and smoking in HNSCC and hence provide a strong rationale for targeting EphB4 for HNSCC therapies.     

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.     

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

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.     

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.     

WT1基因在头颈部鳞状细胞癌中的表达及临床意义

目的检测头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）组织中的Wilms’tumor gene 1（WT1）基因在mRNA及蛋白水平的表达情况,分析其与各临床病理特征的关系。方法应用实时荧光定量PCR法检测46例HNSCC组织及20例正常咽部黏膜组织中的WT1 mRNA表达情况,同时应用免疫组织化学法检测两组石蜡切片中的WT1蛋白表达情况。结果① 46例HNSCC组织WT1mRNA表达均值为9.61×10-3,较正常咽部黏膜组均值1.18×10-4 显著增高(P<0.05);② WT1mRNA表达与肿瘤的分化程度显著相关,分化越差表达越高(P<0.05),且WT1表达在下咽癌组织及嗜酒人群中表达亦显著增高(P<0.05);③ WT1蛋白在HNSCC组织中阳性率为76.09%,而正常咽部黏膜组织无表达,两者差异具有统计学意义(P<0.05)。结论HNSCC组织中WT1在mRNA及蛋白水平均有异常过表达,可能扮演癌基因的角色,参与了肿瘤的发生和发展。     

头颈部鳞状细胞癌的靶向治疗研究进展

头颈部肿瘤是常见肿瘤之一,超过95%的病理类型是鳞状细胞癌,手术与放化疗结合的综合治疗方案是头颈部鳞状细胞癌(HNSCC)的主要治疗方案,但是总体生存率并不高,主要原因是肿瘤复发和/或转移;同时复发性或转移性HNSCC常无法进行手术治疗,放化疗效果也差。靶向治疗的发现为HNSCC、特别是复发性或转移性HNSCC的治疗提供了新的方法。为了进一步认识靶向治疗的临床治疗作用,就HNSCC的靶向治疗研究进展做一综述。