Expression of epidermal growth factor receptor in glottic carcinoma and its relation to recurrence after radiotherapy.

The expression of EGFR was determined immunohistochemically in two groups of patients with glottic carcinoma, one that recurred after a full course of radiotherapy and one that did not. Using a 4-graded scale (-,+,++, ) 80% (12/15) of the recurrent carcinomas had a staining intensity and proportion of stained cells of ++ or more. The same figure for non-recurrent carcinomas was 39% (7/18). The difference is statistically significant (chi-squared with Yates' correction, P less than 0.05). The results indicate that an increased expression of EGFR may influence the rate of recurrence of glottic squamous cell carcinoma after radiotherapy.     

喉癌组织中核表皮生长因子受体与Aurora-A激酶的表达及其临床意义

目的 分析喉癌组织中核表皮生长因子受体(nuclear EGFR)、Aurora-A激酶的表达及其在评价喉癌生物学行为和预后中的价值。方法 回顾性分析50例喉癌患者临床病理资料及随访结果,免疫组化法检测肿瘤组织中核表皮生长因子受体(EGFR)、Aurora-A激酶的表达。结果 50例喉癌患者的组织中,核EGFR、Aurora-A激酶阳性表达率分别为50%(25/50)、58%(29/50),均高于癌旁组织(P<0.05);核EGFR的表达与喉癌的原发灶分期、区域淋巴结转移、复发有关(P均<0.05);Aurora-A的表达与原发灶分期、区域淋巴结转移有关(P值均<0.05);核EGFR与Aurora-A表达的相关分析差异有统计学意义(r=0.446,P<0.05);Kaplan Meier生存分析显示患者3年和5年生存率分别为84.0%和67.8%,Log-rank检验显示原发灶分期、区域淋巴结转移、核EGFR、Aurora-A的表达和患者预后有关(P<0.05)。Cox比例分析模型分析显示原发灶分期、区域淋巴结转移、核EGFR表达为影响喉癌患者预后的独立危险因素(P<0.05)。结论 在喉癌发生和发展过程中存在核EGFR、Aurora-A激酶的异常表达,并与肿瘤的生物学行为和预后有关。     

Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy

OBJECTIVE: TNM staging system is not a sufficiently accurate method for predicting the response of an individual patient to a course of radiotherapy. After irradiation, it can become very difficult to assess data obtained by imaging and endoscopy for the diagnosis of both minimal persistent disease and early recurrence. The search for biological parameters that could be used to identify patients who will respond to radiotherapy is crucial. At this study we aimed at evaluating the prognostic significance of immunohistochemical expression of Ki-67, p53 and epidermal growth factor receptor (EGFR) in laryngeal glottic cancer involving the anterior commissure and treated with radiotherapy. METHODS: From January 1995 to August 2005, 24 patients with glottic cancer involving the anterior commissure were primary treated with radiotherapy. Six patients presented with T1a, 12 patients with T1b and 6 patients with T2. Biopsies were taken before the radiotherapy treatment started. Radiotherapy was done with the same technique for all patients using a linear accelerator device with beam energy of 4-MV photons. Immunohistochemical staining was performed using avidine-biotin-peroxidase technique with antibodies to Ki-67, p53 and EGFR. RESULTS: p53 and EGFR positive expression values and labeling indices were greater in radioresistant than in radiosensitive tumors but without significant differences. On the other hand, Ki-67 was expressed in all radiosensitive tumors and Ki-67 labeling indices were significantly higher in radiosensitive tumors than radioresistant tumors (p=0.01). CONCLUSION: We identified overexpression of Ki-67 as predictive marker of radiosensitivity in glottic cancer involving the anterior commissure, with the results showing significant difference between radiosensitive and radioresistant tumors.     

Expression of epidermal growth factor receptor in the inverted papilloma and squamous cell carcinoma of nasal cavity

The present study was undertaken to compare positive rate of immunostaining (PR) and positive intensity of immunostaining (PI) of epidermal growth factor receptor (EGFR) in inverted papilloma (IP), synchronous carcinoma with IP and metachronous carcinoma with IP of the nasal cavity. Ten subjects with nasal polyps, ten subjects with inverted papilloma (IP), five subjects with synchronous carcinoma with IP and ten subjects with metachronous carcinoma with IP were enrolled with a control group of ten subjects of inferior turbinate. Each specimen was divided into two portions: one for RNA isolation and the other for detection of EGFR protein. Positive rate of immunostaining, positive intensity of immunostaining for EGFR protein and EGFR mRNA were significantly up-regulated in the IP, synchronous carcinoma with IP and metachronous carcinoma with IP when comparing polyp and normal mucosa. A role for EGFR in the malignant transformation from IP to SCC of the nasal cavity is suggested.     

Expression of epidermal growth factor receptor in laryngeal dysplasia and carcinoma

The immunoreactivity of epidermal growth factor receptor (EGFR) was studied in laryngeal biopsy specimens from 24 patients. The study comprised 5 cases of normal laryngeal mucosa, 5 cases of dysplasia, 7 cases of well differentiated squamous cell carcinoma, and 7 cases of poorly to moderately differentiated squamous cell carcinoma. EGFR was in general not expressed in normal and dysplastic epithelia, whilst all carcinomas showed a rather strong positive immunoreactivity. There was no significant difference in staining patterns between the well and poorly to moderately differentiated carcinomas. The results suggest that EGFR constitutes a component of neoplastic, but probably not preneoplastic, laryngeal disease. The study failed to reveal any difference in staining pattern between different types of laryngeal squamous cell carcinoma.     

The role of supracricoid laryngectomy for glottic carcinoma recurrence after radiotherapy failure: a critical review

Conclusions.In the near future salvage supracricoid laryngectomy (SCL) will be used more extensively for failures of radiotherapy for glottic carcinoma. Objectives. Primary radiotherapy has been used for patients with early glottic carcinomas in northern Europe and North America for more than half a century. Local recurrences after radiotherapy for glottic malignancies occur in 5–25% for T1 carcinomas and in 15–50% for T2 carcinomas. The classic choice as salvage surgery in cases of glottic squamous cell carcinoma recurrence after irradiation failure is total laryngectomy. The development of extended conservation procedures such as SCL has permitted an increasing number of successful partial laryngectomies that save laryngeal functions after radiotherapy failure. SCL allows the creation of a neo-larynx, permitting both swallowing and speech; in most cases the tracheostoma can be closed. Methods. The electronic database Pubmed was searched without publication date limits. Results. Considering available data (103 cases), 84.5% of the cases treated with salvage SCL for irradiation failure did not present a new local recurrence; laryngeal recurrences after salvage SCL (15.5%) were successfully treated with total laryngectomy in 66.7% of the cases. Tracheostoma closure was possible in all except two cases after a mean period ranging between 12 and 28 days. Swallowing results seemed good, with longer recovery time in irradiated than in non-irradiated patients who underwent SCL. Voice quality determined with psychoacoustic methods had acceptable intelligibility.     

Expression and clinical significance of epidermal growth factor receptor and type 1 insulin-like growth factor receptor in nasopharyngeal carcinoma

OBJECTIVES: Epidermal growth factor (EGF) and type 1 insulin-like growth factor (IGF-1) receptors play an important role in the growth and apoptosis of nasopharyngeal carcinoma (NPC). They were separately found to be associated with prognosis in patients with NPC. To date, their expression correlation and clinicopathologic significance have never been specifically addressed in NPC. METHODS: Seventy-five patients with NPC and 21 noncancerous nasopharyngeal epithelial samples were accrued between 1998 and 2006 in a single hospital. The expressions of EGF and IGF-1 receptors were detected by immunohistochemical staining in the 75 NPC samples and the 21 noncancerous samples. Furthermore, the messenger RNA and protein expressions were assessed by real-time quantitative polymerase chain reaction and the Western blot technique, respectively, in NPC cell lines and normal nasopharyngeal epithelial cells. RESULTS: The 5-year survival rates, assessed by the Kaplan-Meier method, were 71.4% and 66.6% in the EGF and IGF-1 receptor protein-negative groups, respectively, whereas they were only 28.6% and 33.3% in the receptor protein-positive groups. The levels of these two proteins significantly correlated with each other, and the overexpression rates of EGF and IGF-1 receptors were 65.3% and 56% in nasopharyngeal samples, respectively. Furthermore, both protein expressions were significantly higher in NPC patients with cervical lymph node or distant metastasis than in NPC patients without lymph node or distant metastasis. Recurrence more often appears in cases positive for both proteins than in cases negative for both proteins. The expression levels of the receptor messenger RNA and proteins were higher in several NPC cell lines than in normal nasopharyngeal epithelial cells. CONCLUSIONS: These findings demonstrate that both receptor proteins may play an important role in the invasion, metastasis, and recurrence of NPC. Both receptors are valuable markers for assessing the prognosis of NPC. Their expression at such high frequencies provides the basis of combined targeted therapy with specific pharmacologic inhibitors to enhance the effects of radiotherapy and chemotherapy.     

Expression of epidermal growth factor receptor and its ligands in chronic sinusitis

The epidermal growth factor receptor (EGF-R) system plays a crucial role in mucus production in vitro and in rats. However, the role of the EGF-R system in humans is not known. We compared the localization of EGF-R and its ligands (epidermal growth factor and transforming growth factor alpha) in the epithelia of sinuses with chronic sinusitis and in those of healthy controls. Immunohistochemical techniques were employed to identify the presence of EGF-R and its ligands in the sinus mucosa. We found EGF-R in goblet cells, basal cells, and submucosal gland cells, but not in ciliated cells. Immunoreactivity for both epidermal growth factor and transforming growth factor alpha was found in the epithelial cells and inflammatory cells and in some submucosal gland cells. There was stronger staining of EGF-R and its ligand proteins in chronic sinusitis specimens than in controls. The interrelated localization of EGF-R and its ligands suggests a role in mucus production in the epithelium of the sinus mucosa.     

Immunohistochemical expression of epidermal growth factor receptor and cyclooxygenase-2 in pediatric nasopharyngeal carcinomas: no significant correlations with clinicopathological variables and treatment outcomes

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were separately found associated with prognosis in adult patients with nasopharyngeal carcinoma (NPC). To date, their expression patterns and prognostic utility have never been specifically addressed in children and adolescents. Thirty consecutive NPC patients aged相似文献   

表皮生长因子受体及血管内皮生长因子在喉乳头状瘤中的表达

目的探讨表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）在喉乳头状瘤（IJP）中的表达及意义。方法采用免疫组化二步法检测10例成人型喉乳头状瘤（ALP）、19例幼年型喉乳头状瘤（JLP）石蜡标本中EGFR、VEGF的表达与分布;并以10例声带息肉作为对照组。结果EGFR和VEGF在ALP、JLP组上皮层的表达水平明显高于对照组（P〈0．05）。EGFR在ALP、JLP表皮组织全层均有强阳性表达,VEGF呈现以基底层、棘层细胞显著表达,到颗粒层表达逐渐减弱的模式。VEGF在ALP、JLP和对照组间质的血管内皮细胞、炎症细胞、成纤维细胞中也有表达,但3组问VEGF的表达元显著统计学差异（P〉0．05）。JLP组上皮中VEGF的表达评分结果（7．133±0．061）比ALP组（6．934±0．041）高,两组比较有统计学意义（P〈0．05）。结论VEGF、EGFR在LP组织中的过度表达可能在LP的上皮细胞过度增生和血管大量形成中发挥重要作用,JLP比ALP具有更强的增殖活性。     

Ploidy status and the response of T1 glottic carcinoma to radiotherapy

Flow cytometric DNA ploidy measurements were performed on formalin fixed paraffin embedded tumour specimens from patients with a T₁ glottic laryngeal carcinoma in order to evaluate the role of DNA content in relation to local control. From 1980 to 1987, a consecutive series of 90 patients with a T₁ glottic laryngeal carcinoma were treated by radiotherapy with curative intent. Biopsies from 44 of these patients were readily available for DNA flow cytometry. In this group aneuploidy was associated with a significantly higher risk (P= 0.018) of local recurrence within 2 years after completion of radiotherapy (38% vs. 9% in the diploid group).     

Prognostic significance of epidermal growth factor receptor in squamous cell carcinoma of the maxillary sinus

Summary The expression of epidermal growth factor receptor (EGFR) was determined immunohistochemically in two groups of maxillary sinus squamous cell carcinomas, one with recurrences at the primary site after combination therapy with radiotherapy, chemotherapy and/or surgery and one without local recurrences. Using a four-graded scale (-,+,++,+++), 9 of the 10 recurrent carcinomas had a staining intensity and proportion of stained cells of ++ or more. A comparable staining intensity was found in 9 of the 18 non-recurrent carcinomas. This difference is statistically significant (Fisher's exact probability test, P < 0.05). These results indicate that an increased expression of EGFR may influence the recurrence rate of squamous cell carcinoma of the maxillary sinus after combined therapy.     

Voice quality after laser surgery or radiotherapy for T1a glottic carcinoma

OBJECTIVE: To compare the effect on phonation of radiotherapy and endoscopic laser surgery for stage T1a glottic squamous cell carcinoma. STUDY DESIGN: Retrospective. METHODS: Patients treated for stage T1a glottic carcinoma from August 1994 to March 2000 and who had been followed for at least 1 year were candidates. Eight patients who underwent radiotherapy and 22 who underwent laser surgery were enrolled. Indirect laryngoscopy and stroboscopic examination were performed, and voice quality was analyzed using standard parameters. RESULTS: Maximum phonation time, average airflow rate, sound pressure level, and average fundamental frequency during unconditional phonation were similar after laser surgery and radiotherapy. However, compared with normal men who were 50 years of age or older, the average fundamental frequency was higher after laser surgery. CONCLUSIONS: Contrary to some reports, the voice quality is minimally affected by laser surgery for T1a glottic carcinoma, and outcome is similar to radiotherapy. The average fundamental frequency is higher than normal after laser surgery, but the effect on the quality of life was trivial.     

Expression of epidermal growth factor, epidermal growth factor receptor and transforming growth factor-alpha in the human fetal inner ear

The expression of epidermal growth factor (EGF), EGF receptor and transforming growth factor (TGF)-alpha was analyzed in the human fetal inner ear using immuno-histochemical methods. EGF receptor was observed only in 9.5-week-old fetal vestibular epithelia. In 14- and 16-week-old fetuses, EGF receptor could not be detected. TGF-alpha was observed strongly in the 9- and 11-week-old vestibular epithelia, whereas only trace amounts were detectable in the 14- and 16-week-old vestibular epithelia. These findings suggest that EGF and TGF-alpha probably have a mitogenic effect in the sensory epithelia of the fetal inner ear, especially at early stages of development.     

The role of supracricoid laryngectomy for glottic carcinoma recurrence after radiotherapy failure: a critical review

CONCLUSIONS: In the near future salvage supracricoid laryngectomy (SCL) will be used more extensively for failures of radiotherapy for glottic carcinoma. OBJECTIVES: Primary radiotherapy has been used for patients with early glottic carcinomas in northern Europe and North America for more than half a century. Local recurrences after radiotherapy for glottic malignancies occur in 5-25% for T1 carcinomas and in 15-50% for T2 carcinomas. The classic choice as salvage surgery in cases of glottic squamous cell carcinoma recurrence after irradiation failure is total laryngectomy. The development of extended conservation procedures such as SCL has permitted an increasing number of successful partial laryngectomies that save laryngeal functions after radiotherapy failure. SCL allows the creation of a neo-larynx, permitting both swallowing and speech; in most cases the tracheostoma can be closed. METHODS: The electronic database Pubmed was searched without publication date limits. RESULTS: Considering available data (103 cases), 84.5% of the cases treated with salvage SCL for irradiation failure did not present a new local recurrence; laryngeal recurrences after salvage SCL (15.5%) were successfully treated with total laryngectomy in 66.7% of the cases. Tracheostoma closure was possible in all except two cases after a mean period ranging between 12 and 28 days. Swallowing results seemed good, with longer recovery time in irradiated than in non-irradiated patients who underwent SCL. Voice quality determined with psychoacoustic methods had acceptable intelligibility.     

自动定量分析法测定表皮生长因子受体在口咽癌中的定量表达

目的 评价自动定量分析法（automated quantitative analysis,AQUA）测定表皮生长因子受体（epidermal growth factor receptor,EGFR）在口咽部鳞状细胞癌组织中的表达水平,了解其在判定预后中的价值.方法 AQUA系统分析了一个由95例口咽癌石蜡标本组成的组织微阵列中EGFR的表达,并进行临床和组织病理学资料的相关性分析,将细胞角蛋白（cytokeratin）设为标志物,将数码相机自动拍摄的显示其表达强度的图像载入自动分析系统,设定了每个微阵列点的肿瘤范围,同时用荧光色素原Cy5的耦连抗体显示靶抗原EGFR,并自动计算EGFR表达的像素密度,将其表达数字化,这样就产生了一个数字化的连续变量,它与单位面积内阳性表达的靶抗原分子数量成正比.按表达变量的中位数划分其表达强弱,分成高、低表达组.结果 ①5年局部复发率,肿瘤组织中EGFR细胞高表达组为57.8%,而低表达组为17.2%,相比有显著的统计学意义（P＜0.01）;在肿瘤组织中EGFR细胞核高表达组的5年局部复发率为54.4%,低表达组为21.4%,相比也有统计学意义（P＜0.05）;②在5年无瘤生存率方面,EGFR肿瘤细胞高表达组（19.0%）及细胞核高表达组（19.0%）,分别与细胞低表达组（43.4%）和细胞核低表达组（44.8%）相比也有显著的统计学差异（P均＜0.05）;③多变量风险回归分析,肿瘤细胞和细胞核EGFR高表达都是一个独立的预后负相关因子,有统计学意义.结论 AQUA系统可以有效地对石蜡组织切片中EGFR的表达进行连续变量分析,揭示了EGFR的表达与其产生的生物学作用的联系,EGFR的AQUA数值有望成为能预测EGFR靶向治疗敏感性的一个生物学指标.     

An overview of the role and inter‐relationship of epidermal growth factor receptor,cyclin D and retinoblastoma protein on the carcinogenesis of squamous cell carcinoma of the larynx

rafferty m .a ., fenton j .e . & jones a .s . (2001) Clin. Otolaryngol. 26, 317–320 An overview of the role and inter‐relationship of epidermal growth factor receptor, cyclin D and retinoblastoma protein on the carcinogenesis of squamous cell carcinoma of the larynx Recent developments in both molecular and cellular biology have improved the understanding of the tumorigenesis of laryngeal squamous cell carcinoma. Loco‐regional recurrence of this condition still poses a significant oncological management dilemma for a subset of these tumours. Therefore, the possibility that specific tumour characteristics (demonstrable by immunohistochemical and molecular biological study) may aid the clinician in choosing the optimal treatment for a specific tumour holds great promise. This article concentrates on the role and inter‐relationship of epidermal growth factor receptor status on the function of cyclin D, and how this is related to the presence of retinoblastoma protein. A review of recent studies evaluating these markers, the potential clinical utility of these findings and the possible directions for further study are discussed.     

Northern印迹法检测喉鳞状细胞癌中表皮生长因子受体mRNA的表达

目的 :探讨喉部鳞状细胞癌的发病机制。方法 :采用Northern印迹法检测喉部鳞状细胞癌中表皮生长因子受体mRNA的表达。结果 :在喉部鳞状细胞癌中可见 5 80 0mRNA异常表达。结论 :喉部鳞状细胞癌的生物学行为与其 5 80 0mRNA介导异常表达密切相关。