46例下咽癌的临床病理分析及GLUT-1、HIF-1α在头颈部鳞状细胞癌中的表达及临床意义
发布时间：2018-09-06 13:19
【摘要】：背景和目的：下咽癌的确切病因至今并不清楚,其发病率较其他头颈部位者低,但因下咽位置比较深在、隐蔽,下咽癌早期症状没有特异性,其早期诊断较为困难,患者就诊时多已是晚期,较早常见颈部转移,常浸润喉、口咽、颈段食管和咽旁间隙等,5年生存率通常低于50%,是预后最差的头颈部恶性肿瘤之一,对于下咽癌的治疗,目前主要还是手术、放疗和化疗,而且更趋向于综合治疗。但是,不管是何种治疗,目前预后都不是很理想,影响其预后的真正原因尚不明了。本课题拟分析46例下咽癌患者临床病理因素和生存率的相关性,寻求影响预后的相关临床病理因素。 材料与方法：收集2006.1～2012.1期间我院耳鼻咽喉科收治的46例下咽癌病例进行回顾性分析,观察患者年龄、性别、肿瘤分化程度、TNM分级、临床分期、治疗方式、随访结果,分析与预后之间的关系。 结果 一、46例下咽癌的临床特点 男性44例,女性2例,年龄43～77岁,平均61.3岁。病史(到就诊住院时间)从1个月～10年,肿瘤位于35例位于梨状窝,1例位于环后区,9例位于咽后壁,原发肿瘤不能评估1例。TNM分级：TjNoMo8例,T2NoMo5例,T3NoMo6例,T4NoMo2例,T1N1Mo2例,T2N1Mo8例,T3N1Mo6例,T2N2Mo3例,T3N2M01例,T4aN1Mo2例,T4aN2Mo2例,TxNoMo1例；临床分期Ⅰ期8例,Ⅱ期5例,Ⅲ期22例,Ⅳa期11例。46例中手术切除21例,手术+术后放化疗20例,5例仅放化疗,其中31例(67.4%)保留喉功能。26例行保留喉功能手术,术后1例(3.8%)出现出血再次手术止血；24例手术后14天能正常进食无呛咳,2例(7.7%)出现呛咳,经进食训练1～3周后恢复吞咽功能；25例(96.2%)术后2～3周拔除气管套管,1例(3.8%)因双侧声带固定于正中位未能拔管,戴管出院。 随访时间3个月～75个月,平均31个月。46例中11例死亡,失访4例,平均中位生存时间为57.5个月。其中11例(23.9%)患者复发,4例(8.7%)发生远处转移4例均为肺转移,其中1例合并骨转移。8例(17.4%)为多原发癌。单因素分析,生存率与临床资料的关系中：T分期与总的生存率有关,T1+T2总生存率为55.6%,T3+T4总生存率为35.0%(p=0.029,),T1+T2期3年、5年生存率分别为83.5%、55.6%,T3+T4期3年、5年生存率分别为46.6%、35.0%；复发与生存率有关,复发的总生存率为29.1%,无复发的生存率为51.8%(p=0.005,),无复发的3年、5年生存率分别为80.6%、51.8%,复发的3年、5年生存率分别为29.1%、29.1%；其它指标年龄、肿瘤位置、临床分期、病理分级、有无远处转移、有无多原发癌、治疗方法与总体生存率无统计学差异。采用Cox Regression多因素分析,发现仅T分级与总体生存率有统计学差异(p=0.033)。 结论 1.本组资料显示,46例下咽癌23.6%出现复发,17.4%出现多原发癌； 2.单因素分析,46例下咽癌总的生存率与T分期、复发有关,多因素分析显示仅T分期是独立的预后影响因素； 3.保留喉功能与否的治疗,对下咽癌的生存率没有影响,提示下咽癌的保留喉功能手术切实可行 背景和目的随着免疫学、分子生物学技术的进步和不断发展,现在大多数学者认为肿瘤的浸润和转移是多因素、多步骤的发展过程,基因表达是其重要的机制之一因此,从分子水平探讨头颈部鳞状细胞癌发生、发展的机制,对于认识头颈部鳞状细胞癌的发病机制、判断预后、发现潜在的治疗靶点具有重要意义。 我们前期研究发现葡萄糖转运蛋白-1(glucose transporter-1,Glut-1)的表达与头颈部癌的一些生物性行为有关,但这种结果同样存在着争议。因此,Glut-1在头颈部鳞状细胞癌中的意义,需进一步研究。缺氧诱导因子(Hypoxia inducible factor, HIF)是Glut-1的调节基因,HIF-1α和Glut-1均为肿瘤缺氧的标记,两者共同表达是癌预后差的标记。在头颈部鳞癌中很少见两者联合表达与生物性行为之间相互关系的报道的,而在下咽癌未见的类似报道。采用免疫组织化学方法检测下咽癌组织及喉癌组织中HIF-1α和Glut-1蛋白的表达,分析两者与头颈部鳞状细胞癌的预后及其它生物性行为之间的关系,探讨HIF-1α和Glut-1影响HNSCC预后的可能作用。 材料与方法69例病理确诊的头颈部癌,其中23例下咽鳞癌、46例喉癌。免疫组织化学EliVisionTM法检测上述标本的HIF-1α和Glut-1蛋白表达情况分析各临床病理因素以及HIF-1α和Glut-1表达与生存率的相关性。 结果：头颈部鳞癌Glut-1免疫组化染色阳性率(72.5%)显著高于声带息肉和黏膜白斑病(33.3%)(P0.01)。头颈部鳞癌HIF-1α免疫组化染色阳性率(71.0%)显著高于声带息肉和黏膜白斑病(13.3%)(P0.01)。Pearson Chi-Square分析：单因素分析年龄、性别、部位、T分期、N分期、病例分型、复发和远处转移这8个临床因素与GLUT-1、HIF-1α的相关性,结果显示Glut-1表达与肿瘤位置、N分期和远处转移有关(P0.05),HIF-1α阳性表达与复发、远处转移有统计学意义(P0.05)69例HNSCC中Glut-1、HIF-1α两者共同阳性表达37例,经Pearson相关性分析：两者的表达有一定的相关性(r=0.338,P=0.004) 69例头颈部鳞状细胞癌的总生存率与肿瘤的原发部位、T分级、临床分期、淋巴结转移、复发、远处转移、Glut-1阳性表达、HIF-1α阳性表达有关。Glut-1阳性表达的HNSCC患者的3年、5年生存率分别为：46.7%、37.3%,无Glut-1表达的HNSCC患者的3年、5年生存率分别为：87.5%、82.4%；HIF-1α阳性表达的HNSCC患者的3年、5年生存率分别为：61.0%、42.7%,无HIF-1α表达的HNSCC患者的3年、5年生存率分别为：85.0%、78.5%。Cox Regression比例风险模型多因素分析：发现肿瘤原发位置(p=0.031)、肿瘤局部复发(p=0.000)与总体生存率有统计学差异。 结论 1.本组资料显示Glut-1、HIF-1α表达增高与头颈部鳞状细胞癌的发生可能有关：与炎性病变组织、癌前病变组织相比,头颈部鳞状细胞癌组织中Glut-1表达增高明显； 2. Glut-1表达增高与头颈部鳞状细胞癌位置、N分期和远处转移有关；HIF-1α表达增高与头颈部鳞状细胞癌的复发、远处转移有关； 3.单因素预后分析：Glut-1表达及HIF-1α表达,连同肿瘤的原发部位、T分级、临床分期、淋巴结转移、复发、远处转移与头颈部鳞状细胞癌的预后有关；多因素分析,肿瘤原发位置、肿瘤局部复发与头颈部鳞状细胞癌的预后有关。
[Abstract]:BACKGROUND AND OBJECTIVE: The exact etiology of hypopharyngeal carcinoma is still unclear. The incidence of hypopharyngeal carcinoma is lower than that of other head and neck cancers. However, because the hypopharyngeal position is deep and concealed, the early symptoms of hypopharyngeal carcinoma are not specific, it is difficult to make early diagnosis. The 5-year survival rate is usually less than 50%. It is one of the worst prognosis head and neck malignancies. At present, the treatment of hypopharyngeal cancer is mainly surgery, radiotherapy and chemotherapy, and more inclined to comprehensive treatment. However, no matter what kind of treatment, the prognosis is not very good, the real reason affecting the prognosis is still unknown. To analyze the correlation between clinicopathological factors and survival rate in 46 patients with hypopharyngeal carcinoma, and to explore the related clinicopathological factors affecting prognosis.
Materials and Methods: 46 cases of hypopharyngeal carcinoma admitted to our department of Otolaryngology from January 2006 to January 2012 were retrospectively analyzed. Age, sex, tumor differentiation, TNM classification, clinical stage, treatment, follow-up results, and the relationship between prognosis and prognosis were observed.
Result
Clinical characteristics of 46 cases of hypopharyngeal carcinoma
There were 44 males and 2 females with an average age of 61.3 years, ranging from 43 to 77 years. History (to hospital stay) ranged from 1 month to 10 years. The tumors were located in the pyriform fossa in 35 cases, in the posterior ring area in 1 case, in the posterior pharyngeal wall in 9 cases, and primary tumors could not be evaluated in 1 case. TNM grading: TjNoMo8 cases, T2NoMo5 cases, T3NoMo6 cases, T4NoMo2 cases, T1N1Mo8 cases, T2N1Mo8 cases, T3N1Mo6 cases, and T2N2Mo cases. T3N2M01 cases, T4aN1Mo2 cases, T4aN2Mo2 cases, TxNoMo 1 case, clinical stage I 8 cases, stage II 5 cases, stage III 22 cases, stage IVa 11 cases.46 cases of surgical resection, surgery + postoperative radiochemotherapy 20 cases, 5 cases only radiochemotherapy, of which 31 cases (67.4%) retained laryngeal function surgery, postoperative bleeding occurred in 1 case (3.8%) reoperation hemostasis; One patient could eat normally 14 days after operation without coughing, two patients (7.7%) had cough and recovered swallowing function after 1-3 weeks of training, 25 patients (96.2%) had tracheal cannula removed 2-3 weeks after operation, and one patient (3.8%) was discharged from hospital because bilateral vocal cords were fixed in the median.
The follow-up time ranged from 3 months to 75 months, with an average of 31 months. 11 of 46 patients died and 4 were lost to follow-up. The median survival time was 57.5 months. T stage was associated with overall survival rate, which was 55.6% for T1+T2, 35.0% for T3+T4, 83.5% for T1+T2, 55.6% for T1+T2, 46.6% for T3+T4, 35.0% for T3+T4, and 29.1% for recurrence, 51.8% for non-recurrence, and 51.8% for non-recurrence. The 3-year and 5-year survival rates were 80.6% and 51.8%, respectively. The 3-year and 5-year survival rates were 29.1% and 29.1% respectively. Other indicators, such as age, tumor location, clinical stage, pathological grade, distant metastasis, multiple primary cancer, treatment method and overall survival rate were not significantly different. The survival rate was statistically different (p=0.033).
conclusion
1. according to the data of the group, 23.6% of the 46 hypopharyngeal carcinomas recurred, and 17.4% showed multiple primary cancers.
2. Univariate analysis showed that the overall survival rate of 46 cases of hypopharyngeal carcinoma was related to T stage and recurrence. Multivariate analysis showed that only T stage was an independent prognostic factor.
3. The preservation of laryngeal function has no effect on the survival rate of hypopharyngeal carcinoma, suggesting that the preservation of laryngeal function surgery for hypopharyngeal carcinoma is feasible.
BACKGROUND AND OBJECTIVE With the progress and development of immunology and molecular biology technology, most scholars think that tumor invasion and metastasis is a multi-factor, multi-step process of development, and gene expression is one of the important mechanisms. Therefore, to explore the mechanism of the occurrence and development of head and neck squamous cell carcinoma from the molecular level, for understanding the head and neck. The pathogenesis of squamous cell carcinoma of the body, the prognosis, and the potential therapeutic targets are of great significance.
Our previous study found that the expression of glucose transporter-1 (Glut-1) is related to some biological behaviors of head and neck cancer, but this result is also controversial. Therefore, the significance of Glut-1 in head and neck squamous cell carcinoma needs further study. Hypoxia inducible factor (HIF) is Glut-1. HIF-1a and Glut-1 are both markers of tumor hypoxia and co-expression are markers of poor prognosis in head and neck squamous cell carcinoma. The expression of HIF-1a and Glut-1 proteins in human head and neck squamous cell carcinoma tissues was analyzed. The relationship between the expression of HIF-1a and Glut-1 proteins and the prognosis of head and neck squamous cell carcinoma was analyzed. The possible role of HIF-1a and Glut-1 in the prognosis of HNSCC was discussed.
Materials and Methods The expression of HIF-1a and Glut-1 in 69 cases of head and neck carcinoma confirmed by pathology, including 23 cases of hypopharyngeal squamous cell carcinoma and 46 cases of laryngeal carcinoma, was detected by immunohistochemical EliVisionTM method.
Results: The positive rate of Glut-1 immunohistochemical staining in head and neck squamous cell carcinoma (72.5%) was significantly higher than that in vocal cord polyps and leukoplakia (33.3%) (P 0.01). The positive rate of HIF-1a immunohistochemical staining in head and neck squamous cell carcinoma (71.0%) was significantly higher than that in vocal cord polyps and leukoplakia (13.3%) (P 0.01). Pearson Chi-Square analysis: Univariate analysis of age, sex, location, T. GLUT-1 and HIF-1a were correlated with the clinical factors of stage, N stage, case classification, recurrence and distant metastasis. The results showed that Glut-1 expression was correlated with tumor location, N stage and distant metastasis (P 0.05). The positive expression of HIF-1a was correlated with recurrence and distant metastasis (P 0.05). Pearson correlation analysis showed that there was a certain correlation between the two expressions (r=0.338, P=0.004).
The overall survival rate of 69 cases of head and neck squamous cell carcinoma was related to the primary site, T grade, clinical stage, lymph node metastasis, recurrence, distant metastasis, Glut-1 positive expression and HIF-1a positive expression. The 3-year and 5-year survival rates of Glut-1 positive HNSCC patients were 46.7%, 37.3%, respectively, and those without Glut-1 expression were 3-year and 5-year survival rates. The 3-year and 5-year survival rates were 61.0% and 42.7% for HIF-1a positive HNSCC patients and 85.0% and 78.5% for non-HIF-1a positive HNSCC patients respectively. The survival rate was statistically different.
conclusion
1. The increased expression of Glut-1 and HIF-1a may be related to the occurrence of head and neck squamous cell carcinoma. Compared with inflammatory lesions and precancerous lesions, the expression of Glut-1 in head and neck squamous cell carcinoma increased significantly.
2. The increased expression of Glut-1 was related to the location, N stage and distant metastasis of head and neck squamous cell carcinoma, and the increased expression of HIF-1a was related to the recurrence and distant metastasis of head and neck squamous cell carcinoma.
3. Univariate prognostic analysis: Glut-1 expression and HIF-1a expression were associated with the prognosis of head and neck squamous cell carcinoma, including the primary site, T-grade, clinical stage, lymph node metastasis, recurrence and distant metastasis; Multivariate analysis showed that the primary location and local recurrence of the tumor were associated with the prognosis of head and neck squamous cell carcinoma.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R739.63
本文编号：2226469
[Abstract]:BACKGROUND AND OBJECTIVE: The exact etiology of hypopharyngeal carcinoma is still unclear. The incidence of hypopharyngeal carcinoma is lower than that of other head and neck cancers. However, because the hypopharyngeal position is deep and concealed, the early symptoms of hypopharyngeal carcinoma are not specific, it is difficult to make early diagnosis. The 5-year survival rate is usually less than 50%. It is one of the worst prognosis head and neck malignancies. At present, the treatment of hypopharyngeal cancer is mainly surgery, radiotherapy and chemotherapy, and more inclined to comprehensive treatment. However, no matter what kind of treatment, the prognosis is not very good, the real reason affecting the prognosis is still unknown. To analyze the correlation between clinicopathological factors and survival rate in 46 patients with hypopharyngeal carcinoma, and to explore the related clinicopathological factors affecting prognosis.
Materials and Methods: 46 cases of hypopharyngeal carcinoma admitted to our department of Otolaryngology from January 2006 to January 2012 were retrospectively analyzed. Age, sex, tumor differentiation, TNM classification, clinical stage, treatment, follow-up results, and the relationship between prognosis and prognosis were observed.
Result
Clinical characteristics of 46 cases of hypopharyngeal carcinoma
There were 44 males and 2 females with an average age of 61.3 years, ranging from 43 to 77 years. History (to hospital stay) ranged from 1 month to 10 years. The tumors were located in the pyriform fossa in 35 cases, in the posterior ring area in 1 case, in the posterior pharyngeal wall in 9 cases, and primary tumors could not be evaluated in 1 case. TNM grading: TjNoMo8 cases, T2NoMo5 cases, T3NoMo6 cases, T4NoMo2 cases, T1N1Mo8 cases, T2N1Mo8 cases, T3N1Mo6 cases, and T2N2Mo cases. T3N2M01 cases, T4aN1Mo2 cases, T4aN2Mo2 cases, TxNoMo 1 case, clinical stage I 8 cases, stage II 5 cases, stage III 22 cases, stage IVa 11 cases.46 cases of surgical resection, surgery + postoperative radiochemotherapy 20 cases, 5 cases only radiochemotherapy, of which 31 cases (67.4%) retained laryngeal function surgery, postoperative bleeding occurred in 1 case (3.8%) reoperation hemostasis; One patient could eat normally 14 days after operation without coughing, two patients (7.7%) had cough and recovered swallowing function after 1-3 weeks of training, 25 patients (96.2%) had tracheal cannula removed 2-3 weeks after operation, and one patient (3.8%) was discharged from hospital because bilateral vocal cords were fixed in the median.
The follow-up time ranged from 3 months to 75 months, with an average of 31 months. 11 of 46 patients died and 4 were lost to follow-up. The median survival time was 57.5 months. T stage was associated with overall survival rate, which was 55.6% for T1+T2, 35.0% for T3+T4, 83.5% for T1+T2, 55.6% for T1+T2, 46.6% for T3+T4, 35.0% for T3+T4, and 29.1% for recurrence, 51.8% for non-recurrence, and 51.8% for non-recurrence. The 3-year and 5-year survival rates were 80.6% and 51.8%, respectively. The 3-year and 5-year survival rates were 29.1% and 29.1% respectively. Other indicators, such as age, tumor location, clinical stage, pathological grade, distant metastasis, multiple primary cancer, treatment method and overall survival rate were not significantly different. The survival rate was statistically different (p=0.033).
conclusion
1. according to the data of the group, 23.6% of the 46 hypopharyngeal carcinomas recurred, and 17.4% showed multiple primary cancers.
2. Univariate analysis showed that the overall survival rate of 46 cases of hypopharyngeal carcinoma was related to T stage and recurrence. Multivariate analysis showed that only T stage was an independent prognostic factor.
3. The preservation of laryngeal function has no effect on the survival rate of hypopharyngeal carcinoma, suggesting that the preservation of laryngeal function surgery for hypopharyngeal carcinoma is feasible.
BACKGROUND AND OBJECTIVE With the progress and development of immunology and molecular biology technology, most scholars think that tumor invasion and metastasis is a multi-factor, multi-step process of development, and gene expression is one of the important mechanisms. Therefore, to explore the mechanism of the occurrence and development of head and neck squamous cell carcinoma from the molecular level, for understanding the head and neck. The pathogenesis of squamous cell carcinoma of the body, the prognosis, and the potential therapeutic targets are of great significance.
Our previous study found that the expression of glucose transporter-1 (Glut-1) is related to some biological behaviors of head and neck cancer, but this result is also controversial. Therefore, the significance of Glut-1 in head and neck squamous cell carcinoma needs further study. Hypoxia inducible factor (HIF) is Glut-1. HIF-1a and Glut-1 are both markers of tumor hypoxia and co-expression are markers of poor prognosis in head and neck squamous cell carcinoma. The expression of HIF-1a and Glut-1 proteins in human head and neck squamous cell carcinoma tissues was analyzed. The relationship between the expression of HIF-1a and Glut-1 proteins and the prognosis of head and neck squamous cell carcinoma was analyzed. The possible role of HIF-1a and Glut-1 in the prognosis of HNSCC was discussed.
Materials and Methods The expression of HIF-1a and Glut-1 in 69 cases of head and neck carcinoma confirmed by pathology, including 23 cases of hypopharyngeal squamous cell carcinoma and 46 cases of laryngeal carcinoma, was detected by immunohistochemical EliVisionTM method.
Results: The positive rate of Glut-1 immunohistochemical staining in head and neck squamous cell carcinoma (72.5%) was significantly higher than that in vocal cord polyps and leukoplakia (33.3%) (P 0.01). The positive rate of HIF-1a immunohistochemical staining in head and neck squamous cell carcinoma (71.0%) was significantly higher than that in vocal cord polyps and leukoplakia (13.3%) (P 0.01). Pearson Chi-Square analysis: Univariate analysis of age, sex, location, T. GLUT-1 and HIF-1a were correlated with the clinical factors of stage, N stage, case classification, recurrence and distant metastasis. The results showed that Glut-1 expression was correlated with tumor location, N stage and distant metastasis (P 0.05). The positive expression of HIF-1a was correlated with recurrence and distant metastasis (P 0.05). Pearson correlation analysis showed that there was a certain correlation between the two expressions (r=0.338, P=0.004).
The overall survival rate of 69 cases of head and neck squamous cell carcinoma was related to the primary site, T grade, clinical stage, lymph node metastasis, recurrence, distant metastasis, Glut-1 positive expression and HIF-1a positive expression. The 3-year and 5-year survival rates of Glut-1 positive HNSCC patients were 46.7%, 37.3%, respectively, and those without Glut-1 expression were 3-year and 5-year survival rates. The 3-year and 5-year survival rates were 61.0% and 42.7% for HIF-1a positive HNSCC patients and 85.0% and 78.5% for non-HIF-1a positive HNSCC patients respectively. The survival rate was statistically different.
conclusion
1. The increased expression of Glut-1 and HIF-1a may be related to the occurrence of head and neck squamous cell carcinoma. Compared with inflammatory lesions and precancerous lesions, the expression of Glut-1 in head and neck squamous cell carcinoma increased significantly.
2. The increased expression of Glut-1 was related to the location, N stage and distant metastasis of head and neck squamous cell carcinoma, and the increased expression of HIF-1a was related to the recurrence and distant metastasis of head and neck squamous cell carcinoma.
3. Univariate prognostic analysis: Glut-1 expression and HIF-1a expression were associated with the prognosis of head and neck squamous cell carcinoma, including the primary site, T-grade, clinical stage, lymph node metastasis, recurrence and distant metastasis; Multivariate analysis showed that the primary location and local recurrence of the tumor were associated with the prognosis of head and neck squamous cell carcinoma.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R739.63
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