Glottic versus supraglottic tumors: differential molecular profile

Glottis and supraglottis, although anatomically interconnected, are embryologically distinct. Moreover, squamous cell carcinomas arising from these subsites, differ in terms of epidemiology, risk factors, clinical behaviour and prognosis. This study aims to explore any possible differences between their molecular profiles. We investigated in the two tumor types, the expression of epidermal growth factor receptor (EGFR), nuclear factor-κB (NF-κB) and retinoid X receptor α (RXRα), principal signal transducers associated with cancer, as well as cyclooxygenase-2 (COX-2), an enzyme induced in malignant neoplasms. The clinical material includes tumor specimens from 61 patients with laryngeal cancer of glottic or supraglottic origin. Subsite groups were matched for gender, age and histological grade. Paraffin-section immunohistochemistry was performed, to detect the aforementioned molecules. Staining patterns were membranic and cytoplasmic for EGFR, purely cytoplasmic for COX-2, nuclear for RXRα and cytoplasmic, as well as nuclear, for NF-κB. Intense EGFR and RXRα expression was significantly associated with glottic tumor descent (P = 0.011 and 0.001, respectively). No significant relationship was established between neoplasm location and expressions of NF-κB, COX-2. Our results show that tumors emerging from the two laryngeal regions, are different with regard to their molecular constitution. Upregulation of EGFR and RXRα in carcinomas of the glottis, might be important in the design of subsite-specific chemotherapeutic approaches.     

慢性鼻-鼻窦炎中鼻甲黏膜环氧合酶2与上游丝裂原激活蛋白激酶及核因子κB信号通路相关性探讨

目的探讨慢性鼻-鼻窦炎（chronic rhinosinusitis，CRS）患者中鼻甲黏膜环氧合酶2（cyclooxygenase 2，COX-2）与丝裂原激活蛋白激酶（mitogen-activated protein kinase，MAPK）及核因子KB（nuclear factor kappaB，NF-KB）通路关键酶的表达及其相关性，明确其在黏膜炎性反应机制中的作用。方法将24例CRS患者中鼻甲外侧黏膜按海口分型分期标准分为3组（组1为Ⅰ型2期，组2为Ⅱ型2期，组3为Ⅲ型，每组8例），8例正常鼻黏膜作为对照。应用免疫组化和荧光实时定量多聚酶链反应检测COX-2、p38丝裂原激活蛋白激酶（p38MAPK）、细胞外信号调节蛋白激酶（ERK）、c-Jun氨基端激酶（JNK）、NF-KBp65和p50的表达，并分析其相关性。结果COX-2、p38MAPK、ERK和NF-KB在3组CRS中均有表达，强度高于对照组，差异有统计学意义（P值均〈0．05）；3组CRS之间表达差异无统计学意义（P值均〉0．05）；JNK在CRS各组和对照组中均无阳性表达。相关性分析表明：CRS各组中COX-2、p38MAPK、ERK、NF-κB p65及050的蛋白质表达量同mRNA表达水平呈直线正相关（P值均〈O．05）；在同一组CRS中COX-2与p38MAPK、ERK的蛋白质和mRNA表达呈正相关（P值均〈0．05）；CRS各组中COX-2表达与NF-κB p65、p50的核内表达正相关（P〈0．05）。结论CRS中COX-2表达上调，与上游p38MAPK、ERK、NF-κB等信号转导通路具有相关性，提示COX-2在CRS鼻黏膜炎性反应中可能受后者调节。     

慢性鼻-鼻窦炎黏膜组织中核因子-κB的表达及其与DNA结合活性的研究

OBJECTIVE: To study the expression and activation of nuclear factor-kappa B (NF-kappaB) in mucosa of rhinosinusitis. METHODS: The expressions of NF-kappaB p50 and p65 in the mucosa from 18 patients and 10 norms were detected with the method of immunohistochemistry. The activation of DNA-binding proteins which was labelled with 32P-radiolabeled oligonucleotide probe for NF-kappaB was detected with electrophoretic mobility shift assays (EMSA) in mucosa. RESULTS: Plasm of epithelial and glandular cells displayed a strongly positive staining reaction to p65, and nucleus displayed a strongly positive staining reaction to p50 (7.8%-52.1%). There was significantly difference (chi2 = 22.917, P < 0.01). The DNA-binding proteins activity of 18 samples from pcotients with chronic rhinosinusitis (28.14 +/- 16.71) was stronger than that (9.28 +/- 2.84) in normal subjects (t = 4.56, P < 0.05). CONCLUSIONS: The expression and DNA-binding proteins activity of NF-kappaB was enhanceed. It indicated that NF-kappaB was activated in mucosal inflammation of chrinic rhinosinusitis.     

中耳胆脂瘤中核因子-κB的表达与活化

目的研究中耳胆脂瘤中核因子-κB(nuclearfactorkappaB,NF-κB)的表达与活化,深入阐明胆脂瘤的发病机制。方法中耳手术中收集21例中耳胆脂瘤组织及8例正常外耳道皮肤组织,分别采用免疫组化及凝胶电泳迁移阻滞法(electrophoreticmobilityshiftassay,EMSA)检测2种组织NF-κB的蛋白表达分布及DNA结合活性,并进一步以胆脂瘤鳞屑刺激人角质形成细胞系HaCaT,观察细胞NF-κB的活性变化。结果胆脂瘤上皮组织中NF-κB的表达强度显著高于正常表皮组织,其阳性细胞平均积分吸光度分别为0·168±0·051、0·088±0·019(t=4·211,P<0·01),部分胆脂瘤(12/21)上皮细胞出现明显NF-κB的核转位;EMSA结果显示胆脂瘤组电泳带相对密度扫描值平均为(16·5±10·1)%,正常皮肤组则为(1·38±1·24)%,提示胆脂瘤组织中NF-κB的DNA结合活性显著高于正常皮肤组织(t=3·600,P=0·014);在胆脂瘤鳞屑刺激下,HaCaT细胞出现NF-κB的活化,其活性变化与鳞屑组织呈剂量依赖关系。结论NF-κB在胆脂瘤组织中存在异常活化,核因子-κB可能在胆脂瘤的发生和持续发展中起重要作用。     

Association of nuclear, cytoplasmic expression of galectin-3 with beta-catenin/Wnt-pathway activation in thyroid carcinoma

OBJECTIVES: To characterize the localization of galectin-3 in benign and malignant thyroid neoplasms and to correlate this with alterations in beta-catenin and cyclin D1 expression. DESIGN: Immunohistochemical study of 116 paraffin-embedded archival specimens from 113 patients who had undergone thyroidectomy and tissue placed into a commercially available tissue microarray. SETTING: Tertiary care hospital. INTERVENTIONS: Thyroid tissue microarrays were stained by standard immunohistochemical protocols with monoclonal antibodies against galectin-3, beta-catenin, and cyclin D1. MAIN OUTCOME MEASURES: Nuclear and cytoplasmic expression of galectin-3 was correlated with clinical parameters, beta-catenin, and cyclin D1 expression. RESULTS: Both cytoplasmic (56%) and nuclear (42%) galectin-3 expression was observed in most malignant neoplasms but was absent in benign thyroid specimens (P<.001). Among carcinomas, cytoplasmic galectin-3 expression was observed in papillary thyroid carcinomas (82%) and follicular (33%) and medullary (9%) carcinomas but was absent in anaplastic carcinomas (P<.001). Galectin-3 nuclear expression was observed in papillary thyroid carcinomas (62%) and follicular carcinomas (33%) but was undetectable in medullary, anaplastic carcinomas (P<.001). Cytoplasmic but not nuclear galectin-3 was inversely correlated with American Joint Committee on Cancer TNM stage (P = .02). There was a strong correlation between cytoplasmic and nuclear beta-catenin expression and both nuclear (P = .04) and cytoplasmic (P = .003) galectin-3 expression. Similarly, there was a strong association between galectin-3 nuclear (P<.001) and cytoplasmic (P<.001) expression and cyclin D1 expression. CONCLUSION: Cytoplasmic and nuclear galectin-3 expression seem to be associated with activation of the Wnt-signaling pathway in well-differentiated thyroid neoplasms, suggesting that galectin-3 plays a role in thyroid carcinogenesis.     

Simultaneous expression of cyclooxygenase-2 and microsomal prostaglandin E synthase in squamous cell carcinoma of the larynx

CONCLUSION: In laryngeal cancer, arachidonic acid may be metabolized to PGE2 via the cooperative actions of COX-2 and mPGES, which are induced in response to various stimuli. The COX-2-mPGES-PGE2 system may induce differentiation of cancer cells and prevent metastasis, thus improving the survival rate. OBJECTIVE: To examine the expression of COX-1, COX-2, and two downstream enzymes--microsomal PGE synthase (mPGES) and PGD synthase (PGDS)--using immunohistochemistry in human laryngeal squamous cell carcinoma (SCC). PATIENTS AND METHODS: Patients with laryngeal carcinoma were referred to the Department of Otolaryngology for treatment. Formalin-fixed, paraffin-embedded laryngeal carcinoma specimens were obtained from 24 patients. Immunohistochemical expression of COX-1, COX-2, mPGES, LPGDS, and HPGDS was investigated in 24 laryngeal carcinoma samples. RESULTS: Among the carcinomas, cytoplasmic immunoreactivity for COX-2 was found in tumor cells in 18 of 24 cases (72%) and that for mPGES in tumor cells in 23 of 24 cases (92%). The localization of mPGES was very similar to that of COX-2. COX-2 in well-differentiated SCCs was higher than in poorly/moderately differentiated SCCs. In terms of lymph node metastasis, there was a significant difference in COX-2 expression.     

Cyclin-dependent kinase inhibitor p27 is related to cell proliferation and prognosis in laryngeal squamous cell carcinomas.

An immunohistochemical study of both p27 and proliferating cell nuclear antigen (PCNA) was performed on 102 cases of laryngeal squamous cell carcinomas (LSCCs), and large variations in p27 expression were found among the tumours. Reduced expression of p27 was revealed in 54 (52.9 per cent) cases and correlated with tumour size, lymph node metastasis, and clinical stage, but did not correlate with age, sex, tumour site, or tumour grade. A significant positive correlation was found between the percentage of loss of p27 expression and the PCNA index (r = 0.844, p < 0.0001). Reduced expression of p27 was significantly correlated with both reducing disease-free and overall survival by univariate analysis. By multivariate analysis, reduced expression of p27, tumour grade, tumour size, lymph node metastasis as well as clinical stage were independent prognostic factors for overall survival of LSCCs. These findings indicate that reduced expression of p27 may be correlated with the malignant biological behaviour of LSCCs.     

Tissue microarray analysis reveals prognostic significance of COX-2 expression for local relapse in T1-2N0 larynx cancer treated with primary radiation therapy

OBJECTIVE: The purpose of this analysis is to determine whether a significant correlation exists between cyclooxygenase-2 (COX-2) expression and local relapse in a large cohort of patients with T1 to 2N0 laryngeal cancer treated with primary radiation therapy. METHODS AND MATERIALS: Clinical and molecular analyses were conducted on 123 patients with biopsy-proven T1 to 2N0 laryngeal cancer. Clinical prognostic factors included pretreatment hemoglobin, age, sex, race, T stage, tumor subsite, beam energy, biologically equivalent dose, therapy duration, and treatment date. Molecular prognostic factors included COX-2, p53, and Ki-67 expression. Expression levels were determined by immunohistochemistry on paraffin-embedded tissues arrayed on tissue microarrays. Multivariate analysis was done with the Cox proportional hazards model. RESULTS: Thirty-two patients have locally relapsed, for an actuarial 5-year local relapse-free rate of 70.4%. On multivariate analysis, positive COX-2 expression predicted local relapse after radiation therapy. The relative risk (RR) for local relapse with COX-2 positivity was 2.57 (95% CI, 1.21-5.47; P = .01). Other prognostic factors for local relapse included negative Ki-67 expression (RR = 5.72; 95% CI, 2.04-16.1; P < .001), T2 stage (RR = 2.98; 95% CI, 1.39-6.38; P = .005), and therapy duration greater than 43 days (RR = 6.04; 95% CI, 1.37-26.7; P = .02). CONCLUSIONS: Positive COX-2 expression predicts for local relapse in T1 to 2N0 larynx cancer in a multivariate model. This relationship may have potential therapeutic implications regarding the use of COX-2 inhibitors during radiation therapy for optimal outcome.     

硼替佐米对喉鳞状细胞癌细胞的放射增敏作用的体内外研究

目的 探讨蛋白酶抑制剂硼替佐米对喉鳞状细胞癌(简称鳞癌)Hep-2细胞的放射增敏作用及其机制.方法 体外培养的Hep-2细胞在100 nmol/L的硼替佐米作用2 h后,经过0、2、46、8及10 Gy照射后,检测其放射敏感性的变化,并通过建立的裸鼠移植瘤模型验证其体内放射增敏作用.利用Trans AMTM NF-κB P65活性测定试剂盒检测硼替佐米对Hep-2细胞辐射诱导NF-κB活化的影响;用流式细胞仪分析细胞周期及照射前后的细胞凋亡;Hoechst 33342荧光染色法观察细胞凋亡状况.结果 克隆形成实验显示硼替佐米可增加Hep-2细胞的放射敏感性34%.裸鼠移植瘤模型的肿瘤生长延迟放射增敏值为1.46.经2 Gy和8 Gy照射后2 h可诱导NF-κB活化,且存在剂量相关性(r=0.989,P<0.05).硼替佐米在0、2、8 Gy不同的照射剂量均能降低Hep-2细胞NF-κB的活性(t值分别为20.02、14.20、17.46,P<0.01);经硼替佐米干预的细胞有明显的G2-M期阻滞作用(t=22.31,P=0.000),并在照射后明显的细胞凋亡率增加(P值均<0.01).Hoecht 33342染色可见细胞核均匀染色,凋亡细胞的核凝集,呈强蓝色荧光,细胞核碎裂呈花瓣状.硼替佐米照射组凋亡比例高于单纯照射组.结论 硼替佐米通过可影响Hep-2细胞的细胞周期分布、诱导细胞凋亡及抑制NF-κB活化的途径,从而增加其对放射的敏感性.     

Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto's thyroiditis

OBJECTIVES: Cyclooxygenases (COX) are enzymes that catalyze the conversion of arachidonic acid to prostaglandins. COX-2, unlike the constitutively expressed COX-1, is an inducible enzyme upregulated during cell proliferation and inflammation. More recently, COX-2 has been implicated in the development of numerous types of epithelial cancers. In addition, COX-2 is highly expressed in several inflammatory diseases. Because of its dual role in inflammation and cancer, we were interested in determining if COX-2 plays a role in the development of human thyroid carcinoma and Hashimoto's thyroiditis, an autoimmune condition frequently associated with thyroid malignancy. MATERIALS AND METHODS: Twenty paraffin-embedded human tissue specimens, including normal, inflammatory, and neoplastic thyroid sections, were analyzed by immunohistochemical staining for expression of human COX-2. In addition, COX-2 protein expression was verified by Western blot in two specimens. RESULTS: Immunohistochemical staining confirmed the presence of COX-2 in thyroid epithelial neoplasms, including papillary and follicular carcinomas. Moreover, COX-2 expression was observed in patients with Hashimoto's thyroiditis. COX-2 expression, however, was not observed in normal thyroid tissue, multinodular goiter, or anaplastic carcinoma. CONCLUSIONS: We have shown that cyclooxygenase-2 is expressed in thyroid carcinoma and thyroid epithelium from patients with Hashimoto's thyroiditis but not in normal thyroid. The expression of COX-2 in both of these thyroid pathologies may provide a basis for the relationship between carcinogenesis and autoimmunity.     

克拉霉素对离体鼻息肉组织中环氧合酶-2及核因子κB表达的影响

目的：检测用不同浓度梯度的克拉霉素干预后,离体鼻息肉组织中环氧合酶-2（COX-2）及核因子κB（NF-κB）的表达状况,探讨其在鼻黏膜炎症机制中的作用。方法：将鼻息肉组织块分别与克拉霉素（0、10^-6、10^-5及10^-4mol／L）于体外共同培养1d,应用Western blot和荧光实时定量PCR技术检测COX-2和NF-κB亚基的表达水平,观察克拉霉素干预后COX-2和NF-κB表达的变化规律。结果：对照组（0mol／L克拉霉素组）鼻息肉组织中COX-2、NF-κBp50和NF-κcBp65的蛋白质和核酸表达水平最高;随着克拉霉素干预剂量的增加,COX-2、NF-κBp50和NF—κBp65的表达水平呈剂量依赖性下降。相关分析表明,同一组鼻息肉组织中,COX-2核酸表达量分别与NF-κBp50、NF-κBp65呈直线正相关。结论：COX-2异常表达参与了鼻-鼻窦黏膜慢性炎症反应,克拉霉素可能通过阻断NF-κB通路来下调COX-2的合成,发挥其抗炎作用。     

Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma

An immunohistochemical analysis of over-expression of p53 and c-erbB-2 proteins was performed on 27 biopsies of laryngeal carcinoma. The aim of this study was to investigate whether there is a correlation between over-expression of these proteins and the clinicopathological features of the tumor and to reveal any possible prognostic value. Paraffin sections of laryngeal carcinoma were studied using immunohistochemical staining with mouse and rabbit monoclonal antibodies, respectively, for p53 and c-erbB-2 proteins. The positive controls were paraffin-embedded specimens from ten breast carcinomas previously shown to express these proteins. Ten benign laryngeal nodules were immunohistochemically stained as negative controls. Samples from 74% of 27 patients with laryngeal carcinomas demonstrated positive nuclear and cytoplasmic (or membranous) staining for p53 protein and 48% were positive for c-erbB-2 protein. In the present study, while there was a slight difference in the frequency of p53 over-expression among stage I–II and stage III–IV tumors, there was no difference in the frequency of p53 over-expression among primary and recurrent tumors. There was no statistically significant correlation between over-expression of the p53 and c-erbB-2 proteins and the age of the patients, tumor site, tumor grade, clinical stage, histopathological grading of the tumor, alcohol consumption, and clinical outcome. There was a statistically significant correlation between immunostaining of p53 and c-erbB-2 proteins (P = 0.037). While it was found that over-expression of p53 was significantly associated with the presence of lymph node metastasis (P = 0.006), there was no association between the expression of c-erbB-2 and lymph node status. The data demonstrated increased expression of p53 and c-erbB-2 proteins, presumed to be mutant, in laryngeal carcinomas. Hence, we conclude that p53 and c-erbB-2 over-expression as detected by immunohistochemical staining in larynx carcinomas is not predictive of poor survival or disease-free survival. Received: 20 June 2000 / Accepted: 10 April 2001     

Expression and significance of nuclear factor kappaB in laryngeal carcinoma]

OBJECTIVE: To explore the expression and significance of NF-kappaB in laryngeal carcinoma. METHOD: The protein expression of NF-kappaB p65 in laryngeal carcinoma tissue and normal laryngeal tissue was examined by Western blot; NF-kappaB DNA binding activity was examined by electrophoretic motility shift assay (EMSA) in 20 laryngeal carcinoma tissue and 12 normal laryngeal tissue. RESULT: The levels of NF-kappaB p65 protein and NF-kappaB DNA binding activity in the laryngeal carcinoma tissue were higher than those in normal laryngeal tissue. CONCLUSION: NF-kappaB may be an important oncoprotein and involves in the occurrence and development of laryngeal carcinoma.     

Galectin-3 upregulation during tumor progression in head and neck cancer

Objectives/Hypothesis: To examine the level of expression of galectin-3 in relation to neoplastic progression of hypopharyngeal squamous cell carcinomas (HSCCs) and laryngeal squamous cell carcinomas (LSCCs). Study Design: Retrospective study. Methods: Using a polyclonal antibody against galectin-3 without cross-reactivity to other galectins, we analyzed the presence of galectin-3 using quantitative immunohistochemistry in i) a series of 79 HSCCs compared with 16 normal epithelia, 20 low-grade dysplasia (Low_D) and 25 high-grade dysplasia (High_D) and in ii) a series of 58 LSCCs compared with 34 normal epithelia, 12 Low_D, and 18 High_D. In parallel, galectin-3 expression was studied using Western blotting on a series of 19 fresh biopsies from patients presenting a head and neck tumor. Results: Western blotting excluded a notable degree of proteolytic truncation of galectin-3 in situ. Immunohistochemical galectin-3 positivity expressed as percentage of cells was significantly higher in LSCCs and HSCCs than in Low_D (P = .01) or High_D (P = .0002), respectively. Increased expression of galectin-3 in HSCCs was accompanied by a shift from the cytoplasmic compartment to the nucleus (P = .007). In intertumor-type comparison, laryngeal carcinomas presented nuclear presence of galectin-3 only rarely (1 of 58 cases in laryngeal cancer vs. 27 of 79 cases in hypopharyngeal cancer, P = .00006) and a comparatively low labeling index (P < 10⁻⁶). Conclusions: Our data reveal an association between level of presence of galectin-3 and neoplastic progression of HSCCs and LSCCs.     

Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance

p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n= 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.     

内毒素刺激前后鼻黏膜上皮细胞中Toll样受体4 mRNA及核因子κB p50亚型mRNA的表达及意义

目的探讨内毒素(即脂多糖,lipopolysaccharide,LPS)刺激前后 Toll 样受体4(Tolllike receptor 4,TLR4)mRNA 和核因子 kB(nuclear factor kB,NF-kB)p50亚型 mRNA 在正常鼻黏膜上皮细胞中的表达及意义。方法在15例成人鼻中隔偏曲患者(无鼻-鼻窦炎)矫正术中,取正常中鼻甲外侧黏膜组织各2份行组织外植块培养,其中15份加 LPS 刺激培养为 LPS 组,另外为培养组。应用 HE 染色光镜下观察鼻黏膜组织上皮细胞的病理形态学改变;应用核酸分子原位杂交技术检测离体培养正常鼻黏膜组织上皮细胞中 TLR4 mRNA 和 NF-kB p50 mRNA 的表达情况。结果①LPS刺激后,光镜下见正常鼻黏膜上皮细胞纤毛有粘连成束、胞体增大的病理形态学改变;②LPS 组 TLR4mRNA 表达明显高于培养组;LPS 组表达阳性区平均吸光度为1.283±0.027,培养组为0.538±0.038,二组间差异有统计学意义(t=1.761,P<0.05);③NF-kB p50 mRNA 在 LPS 组均出现阳性表达,而培养组阳性率仅为26.7%。LPS 组明显高表达于培养组,且以胞核表达为主,LPS 组表达阳性区平均吸光度为1.668±0.037;培养组为0.372±0.052,二组间差异有统计学意义(t=2.624,P<0.01)。结论 LPS 能通过 TLR4活化 NF-kB p50,进而激活正常鼻黏膜上皮细胞。这可能在 LPS 对鼻黏膜上皮细胞激活和损伤效应中具有一定的作用。     

喉癌中脉管生成相关因子与微血管密度和淋巴管密度的关系及临床意义

目的探讨喉癌组织中缺氧诱导因子-1α(hypoxia inducible factor 1 alpha,HIF-1α)、环氧化酶-2(cyclooxygenase 2,COX-2)的表达与微血管和淋巴管密度的关系。方法通过免疫组化SP法对64例声门上型喉癌标本中HIF-1α、COX-2与微血管密度(microvessel density,MVD)CD34标记及微淋巴管密度(lymph vessel density,LVD)D2-40标记进行了检测。结果喉癌中HIF-1α及COX-2蛋白阳性表达率分别为67.18%(43/64)、70.31%(45/64),MVD为36.79±8.48,LVD为9.68±6.35。喉癌HIF-1α、COX-2表达阳性者的MVD及LVD明显高于阴性者。喉癌中HIF-1α和COX-2之间存在相关性(r=0.492,P<0.05)。颈淋巴结转移组中HIF-1α、COX-2阳性表达率(χ2分别为6.615、5.534、P<0.05)及MVD和LVD(t分别为5.58、7.43,P<0.05)明显高于非转移组,差异有统计学意义。结论 HIF-1α、COX-2可能参与喉癌的血管及淋巴管生成,HIF-1α可能通过调节下游基因的表达,在喉癌血管及淋巴管生成中发挥重要作用,共同参与喉癌颈淋巴结转移过程。     

Is syndecan-1 an independent prognostic factor in patients with laryngeal carcinoma?

Syndecan-1 is a member of the syndecan family of cell membrane heparan sulphate proteoglicans. The aim of this study was the evaluation of prognostic value of syndecan-1 expression in laryngeal cancer. The findings were correlated with the clinico-pathological parameters of the tumours, as well as with patient survival rate. Paraffin-embedded samples from 99 patients with laryngeal cancer selected from the files of the ENT-Dept. of Medical Academy in Lublin were immunostained with anti-syndecan-1 monoclonal antibody. The patients' mean age was 57 years and the over 5-year survival rate was 53.2%. Syndecan-1 immunoreactivity was observed in 99 (100%) of carcinomas. In our study, a statisti- cally significant correlation between syndecan-1 expression and patient survival rate was observed (chi2 = 9631; p = 0.008) as well as between syndecan-1 expression and various clinical stages of disease (chi2 = 6771; p = 0.034). The significant difference in the presence of syndecan-1 expression among the patients with various stage of histological differentiation of carcinoma (chi2 = 14.9; p = 0.001), and among the patients with present and absent metastatic changes in regional lymph nodes (chi2 = 16.698; p = 0.001) was observed. In a Coxs multivariate analysis syndecan-1 had an independent prognostic value (p = 0.014). Our results indicate that syndecan-1 could be used as a prognostic marker in laryngeal cancer.