Vascular Endothelial Growth Factor Expression Correlates with p53 Mutation and Angiogenesis in Squamous Cell Carcinoma of the Head and Neck

We present a case of squamous spindle cell carcinoma of the external auditory meatus in a 38-year-old man. The tumour was extended to the inner ear, the temporal bone, the middle cranial fossa and the meningo-cerebral tissue. The surgical intervention of temporo-occipital craniotomy removed most of the neoplasia. At pathologic examination, the tumour showed an undifferentiated spindle cell pattern. Immunohistochemistry with a large antibody panel found a weak positivity only to EMA. The diagnosis was made when the electron microscopy showed rare junctional structures and tonofilaments.     

喉癌肿瘤组织HIF-1α与VEGF的表达及意义

目的 研究缺氧诱导因子-1α(hyporia inducible factor-1 alpha，HIF-1α)与喉癌进展的关系，分析喉癌肿瘤组织中HIF—1α与血管内皮生长因子(vascular endothelial growth factor，VEGF)表达的相关性。方法 采用S—P免疫组织化学的方法检测68例不同临床分期及病理分化的喉癌术后标本中HIF-1α与VEGF的表达，同时采用SPSS统计软件分析HIF-1α与VEGF表达的相关性。结果 68例喉癌中41例HIF-1α阳性(60．29％)，46例VEGF阳性(67．65％)，HIF-1α表达与喉癌的分期及病理分级密切相关。喉癌中HIF-1α的表达与VEGF呈正相关。结论 HIF-1α在喉癌的进展中可能具有重要作用，HIF-1α可能具有促进喉癌中VEGF表达的作用。     

Disease Stage Related In Vitro Responsiveness of Peripheral Blood T-lymphocytes in Patients with Head and Neck Carcinoma

The in vitro responsiveness of peripheral blood mononuclear cells (PBMC) T lymphocytes was studied in 81 patients with limited or extended head and neck squamous cell carcinoma (HNSCC), as judged by T, N and T+N stages. Patients included in the study were males below 80 years of age, without auto-immune disease or cachexia, who were not taking any immuno-active medication at the time of diagnosis. The patients were divided into groups according to TNM stage T_0-2 vs T_3-4, N_0-1 vs N_2-3 or T+N_0-3 vs T+N_4-7. When cells from patients with early and late stage, according to T, N or T+N stage, were compared, we found a decreased level of mitogen stimulated T-cells and decreased spontaneous proliferation with increasing disease stage. The same was true if the in vitro     

Identification of Genes Overexpressed in Head and Neck Squamous Cell Carcinoma Using a Combination of Complementary DNA Subtraction and Microarray Analysis

Objectives/Hypothesis To discover unique genes specific for squamous cell carcinoma of the head and neck for eventual development as tumor markers and vaccine candidates. Study Design Molecular biological analysis of fresh‐frozen head and neck squamous cell cancer (HNSCC). Methods A subtractive library was made from two HNSCC and six normal tissues using a polymerase chain reaction (PCR)–based approach. Genes from this library were PCR amplified and placed on a microarray glass slide. RNA was prepared or obtained from 16 fresh‐frozen HNSCC and 22 normal tissue sources. Fluorescent probes were made from the polyA+ RNA derived from the tumor and normal tissues. The probes were hybridized to the glass slides and excited by a tuneable laser. One hundred seven of the genes showing the highest differential fluorescence value between tumor and normal tissue were identified by sequence analysis. Results Thirteen independent genes were found to be overexpressed in tumor tissues. Of these, nine were previously known: keratins K6 and K16, laminin‐5, plakophilin‐1, matrix metalloproteinase‐2 (MMP), vascular endothelial growth factor, connexin 26, 14–3‐3 sigma, and CaN19. The level of polyA+ RNA of these genes in the tumors was significantly different from the levels in normal tissue (P < .05). Four previously unidentified genes were also discovered to have increased expression in tumor tissue. Comparing the total tumor group (n = 16) to the normal group (n = 22), only one of these genes showed significant overexpression. Conclusion We report the identification of nine known genes that are significantly overexpressed in HNSCC as compared to normal tissue using subtractive and microarray technology. In addition, we present four previously unidentified genes that are overexpressed in a subset of tumors. These genes will be developed as tumor markers and vaccine candidates.     

Ki67和VEGF与喉鳞状细胞癌预后关系的探讨

目的：探讨细胞增殖抗原标记物（Ki67）和血管内皮生长因子（VEGF）与喉鳞状细胞癌预后的关系。方法：用免疫组织化学方法研究Ki67和VEGF在32例喉鳞状细胞癌组织中的表达,其中术后3年局部复发5例（复发组）,转移3例（转移组）,死亡8例（死亡组）,生存24例（生存组）。结果：死亡组Ki67和VEGF的表达均明显高于生存组（均P〈0．01）。Ki67在复发组和转移组中高表达,均高于未复发组和未转移组（均P〈0．01）。VEGF在复发组中亦高表达,高于未复发组（P〈0．05）。Cox多因素回归分析发现,Ki67（危险比为3．236,P〈0．01）、喉癌的T分期（危险比为1．382,P〈0．05）和术前淋巴结转移情况（危险比为0．316,P〈0．05）是影响喉鳞状细胞癌预后的独立指标。结论：Ki67和VEGF与喉鳞状细胞癌的预后有关,两指标的高表达预示着喉癌较差的预后,有助于喉癌治疗方案的制定。     

Characteristics of Expression of Matrix Metalloproteinases (MMP-2 and MMP-9) in Glottic Squamous Cell Carcinoma and Benign Vocal Fold Lesions

ObjectivesThe aim of this study was to investigate expression profile of matrix metalloproteinases (MMP-2 and MMP-9) in glottic squamous cell carcinoma (SCC) and benign vocal fold lesions (BVFLs) and to correlate it with clinical and pathological features.MethodsThe immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken from 217 patients group, including vocal fold polyps (n=39), recurrent respiratory papillomatosis (n=30), laryngeal keratosis (n=36), glottic SCC (n=112), and the normal tissue of vocal fold (n=12, control group). The expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 18 points (high expression).ResultsExpressions of both, MMP-2 and MMP-9 were significantly higher in the glottic SCC group comparing with BVFL group. Significant higher expression of parenchymal MMP-2 (P<0.001) and stromal MMP-9 (P=0.01) was revealed in the group of moderate/poorly differentiated glottic SCC comparing with well differentiated glottic SCC group. Expression of stroma MMP-2 was found to be correlated with nodal metastasis (P=0.030). Expressions of both, MMP-2 and MMP-9 were not correlated with clinical stage, tumor T value, smoking, alcohol use, age in the glottic SSC patients group. The MMP-2 stroma value of 11.2 points was determined as the optimum point (limiting value) for separating BVFL and glottic SCC patient groups.ConclusionOur results suggest that expressions of both MMP-2 and MMP-9 are up-regulated already in the development of BVFL, the next determinant step is concerned with occurrence of malignization. Limiting value of stroma MMP-2 demonstrates prognostic importance of MMP-2 in glottic SCC carcinogenesis.     

喉癌中p53蛋白与VEGF表达的相关性研究

目的检测、比较分析喉癌中p53蛋白与VEGF的表达及平均瘤内血管密度的相关性.方法采用S-P免疫组织化学的方法检测62例喉癌术后标本中p53蛋白和VEGF的表达,并计算其平均瘤内血管密度;同时采用SPSS统计软件分析p53蛋白与VEGF的表达及瘤内血管密度的相关性.结果 62例喉癌中,33例p53蛋白阳性,38例VEGF阳性,平均瘤内血管密度为(34.58±11.23)mv;p53蛋白阳性的33例中,25例VEGF表达阳性,平均瘤内血管密度为(39.65±10.66)mv;29例p53蛋白阴性的病例中,13例VEGF表达阳性,平均瘤内血管密度为(30.45±11.76)mv;统计学处理发现p53蛋白阳性的病例中,VEGF表达的阳性率高于p53阴性的病例,平均瘤内血管密度高于p53阴性的病例.结论喉癌中VEGF的表达、平均瘤内血管密度与p53蛋白的表达呈正相关,mut-p53基因可能具有促进喉癌中VEGF表达、促进喉癌中微血管形成,进而促进喉癌细胞的侵袭与转移的作用.     

Expression of the Opioid Growth Factor, [Met5]-Enkephalin,and the Zeta Opioid Receptor in Head and Neck Squamous Cell Carcinoma

Despite the prevalence of cancers of the head and neck, survival rates have not changed in the past few decades. Recent work has implicated peptide growth factors and their receptors in the genesis and progression of head and neck squamous cell carcinoma. Opioid growth factor (OGF, [Met⁵]-enkephalin) is a tonically active, autocrine and/or paracrine produced, inhibitory factor that influences the growth of normal and abnormal cells and tissues. This peptide interacts with the zeta (ζ) opioid receptor to modulate cellular proliferation, migration, and survival. Both OGF and the ζ receptor are present in mammalian tongue epithelium and skin, and modulate DNA synthesis. In the present study we examined the presence and distribution of OGF and theζ opioid receptor in the head and neck squamous cell carcinomas from seven individuals. All specimens expressed this growth factor and its receptor regardless of tumor stage, location, and histologic grade. Immunoreactivity for both OGF and the ζ receptor were associated with the cytoplasm but not the nucleus in cells of each of these carcinomas. Our findings that a potent negative growth regulator and its receptor are present in head and neck squamous cell carcinoma lead us to suggest that OGF may modulate the growth of these types of cancers.     

声门上型喉鳞状细胞癌组织VEGF、MMP-2、eIF4E的表达及临床意义

目的研究声门上型喉鳞癌及癌旁组织中VEGF、MMP-2、eIF4E的表达及与临床病理参数的关系。方法采用免疫组化SP法检测28例声门上喉鳞癌组织及癌旁组织中VEGF、MMP-2、eIF4E的表达。结果在声门上型喉癌组织中VEGF、MMP-2、eIF4E阳性表达率分别为78.57%,75%,89.28%;在癌旁组织中阳性表达率分别为21.42%,17.85%,42.85%。三者在肿瘤组织及癌旁组织中的表达差异有统计学意义(P<0.05),其表达与肿瘤淋巴结转移密切相关(P<0.05),三者间存在正相关。结论VEGF、MMP-2、eIF4E是声门上喉鳞癌组织表达较敏感的标志物,可作为反应喉癌生物学行为的客观参考指标,有助于判断患者预后,及有利于肿瘤治疗方案的制定。     

鼻咽癌中VEGF、bFGF的表达及其与颈淋巴结转移的关系

目的 探讨鼻咽癌中血管生长因子VEGF、bFGF的表达及其与颈淋巴结转移的关系。方法 采用免疫组化S－P法对35例鼻咽癌（其中15例同时取颈部转移癌组织）,20例鼻咽粘膜不典型增生组织和10例慢性炎症组织中VEGF、bFGF的表达进行了检测。结果（1）35例鼻咽癌中17例（48．6％）VEGF表达阳性,明显高于非癌对照组（6．7％,P＝0．000）,有颈淋巴结转移鼻咽癌中VEGF的表达（73．3％）明显高于无颈淋巴结转移者（30％,P＝0．018）;晚期（Ⅲ、Ⅳ期,70．6％）明显高于早期（Ⅰ、Ⅱ期,27．8％,P＝0．018）：但咽癌原发灶中VEGF的表达与颈部转移灶中的表达无相关性（P＞0．05）;（2）35例鼻咽癌中有8例（22．9％）bFGF表达阳性,明显高于非癌对照组（3．3％,P＝0．031）。但鼻咽癌中bFGF的表达与患者的年龄、性别、肿瘤的组织学类型和分期无关,也与肿瘤的N分期无关（P＞0．05）。结论 （1）VEGF与鼻咽癌的生长及颈淋巴结转移有关,它可能可以作为预测鼻咽癌颈淋巴结转移的的指标;（2）bFGF可能与鼻咽癌的生长有关系,但与肿瘤的颈淋巴结转移可能无关。     

Tissue expression,serum and salivary levels of vascular endothelial growth factor in patients with HNSCC

IntroductionVascular endothelial growth factor is thought to be an important angiogenic factor involved in tumor growth, progression, and metastasis.ObjectiveThe present study evaluated the relation between tissue expression, serum and salivary levels of vascular endothelial growth factor in head and neck squamous cell carcinomas, and their correlation with clinicopathologic features.MethodsSamples were collected from 30 patients with head and neck squamous cell carcinomas and 24 healthy volunteers. Immunohistochemical analysis was used for tissue expression and enzyme-linked immunosorbent assay was employed to measure serum and salivary levels.ResultsNo vascular endothelial growth factor staining was observed in normal tissues, whereas vascular endothelial growth factor expression was seen in 6 patients (20%). Mean serum level of VEGF was 83.7 ± 104.47 in patients and 50.04 ± 32.94 in controls. Mean salivary level of vascular endothelial growth factor was 174.41 ± 115.07 in patients and 149.58 ± 101.88 in controls. No significant difference was found by Mann–Whitney test between controls and patients (p = 0.411, p = 0.944, respectively). No correlation was found between vascular endothelial growth factor tissue expression and its serum and salivary level.ConclusionOverexpression of vascular endothelial growth factor was found in head and neck squamous cell carcinoma patients, suggesting its role in the pathogenesis of head and neck squamous cell carcinoma, but no relation was found between tissue expression, serum levels, and salivary levels of this marker.