BRMS1基因蛋白在声门上型喉癌中的表达及临床意义

目的 探讨乳腺癌转移抑制基因（breast cancer metastasis suppressor 1,BRMS1）在声门上型喉鳞状细胞癌组织中的表达及其临床意义。方法 免疫组化法检测60例原发性声门上型喉癌组织(肿瘤组)和其相邻的癌旁正常喉黏膜(对照组)石蜡标本组织细胞中BRMS1蛋白的表达。结果 对照组均有较强的BRMS1蛋白的表达,肿瘤组阳性表达率为35.0%(21/60),且均为低表达,两者之间差异有统计学意义(P＜0.05)。BRMS1蛋白在病理高分化标本中阳性表达率为43.6%（17/39）,在中、低分化标本阳性表达率19.0%（4/21）,两者之间差异有统计学意义（P＜0.05）;在临床Ⅱ期标本阳性表达率为72.7%（8/11）,临床Ⅲ+ Ⅳ期标本阳性表达率26.5%（13/49）,两者之间差异有统计学意义（P＜0.05）;颈部淋巴结N0组标本阳性表达率72.7%（16/22）,颈部淋巴结N+组阳性率13.7%（5/38）,两者之间差异有统计学意义(P＜0.05)。BRMS1蛋白阳性组患者与BRMS1蛋白阴性组患者的术后生存率无统计学差异(P＞0.05)。结论 BRMS1蛋白在声门上型喉癌中低表达或不表达,且其表达可能与声门上型喉癌的临床分期、病理分化以及颈部淋巴结转移有关。     

基质金属蛋白酶11在喉癌中的表达

目的:检测喉癌中基质金属蛋白酶11(MMP11)的表达,探讨MMP11的表达与喉癌浸润和转移的关系.方法:采用免疫组织化学法检测63例喉癌组织和相应的癌旁正常组织MMP11蛋白的表达,运用RT-PCR技术检测22例喉癌和相应的癌旁正常组织冻存标本中MMP11 mRNA水平的表达.结果:采用免疫组织化学法检测喉癌和癌旁正常组织MMP11的表达,癌组织MMP11的表达阳性率明显高于癌旁正常组织(P＜0.01).运用RT-PCR方法检测喉癌和癌旁正常组织MMP11 mRNA的表达,癌组织MMP11 mRNA的表达阳性率明显高于癌旁正常组织(P＜0.01).MMP11蛋白表达在T3 T4组高于T1 T2组(P＜0.01),淋巴结转移组高于非淋巴结转移组(P＜0.05).MMP11 mRNA表达在T3 T4组高于T1 T2组(P＜0.05),淋巴结转移组高于非淋巴结转移组(P＜0.05).MMP11蛋白及MMP11 mRNA的表达与肿瘤原发部位和分化程度无明显相关性(P＞0.05).结论:MMP11的表达与喉癌浸润和转移密切相关,可作为预测喉癌浸润和转移潜能的参考指标之一.     

喉癌组织中抑癌基因PTEN的表达及意义

目的检测抑癌基因PTEN在喉癌组织的表达情况,探讨PTEN与喉癌发生发展之间的关系. 方法采用免疫组织化学SABC染色法观察正常喉黏膜和喉癌组织中PTNE蛋白的表达,并比较分析其与肿瘤生长部位、病理分级、临床分期和淋巴转移的关系. 结果 PTNE在喉癌组织的表达阳性率(52.3%)明显低于正常喉黏膜组织的表达阳性率96.7%,(P＜0.05);Ⅰ、Ⅱ期喉癌(71.4%、63.3%)PTEN蛋白表达阳性率又明显高于Ⅲ、Ⅳ期喉癌(25.0%、22.2%),(P＜0.05);声门型喉癌(65.8%)明显高于声门上型和声门下型喉癌(34.8%、25.0%),(P＜0.05);高分化喉鳞癌(88.0%)明显高于低分化喉鳞癌(37.5%、18.8%),(P＜0.05);N0喉癌(78.4%)明显高于N1、2喉癌(17.9%),(P＜0.05). 结论 PTNE在喉癌的发生及发展过程中有表达缺失,缺失程度与临床分期、生长部位、病理分级和淋巴转移有相关性.     

声门上型喉癌组织中的BRMS1蛋白表达及甲基化的研究

目的:探讨声门上型喉鳞状细胞癌组织中乳腺癌转移抑制基因(BRMS1)的蛋白表达以及BRMS1基因启动子区域甲基化情况及其临床意义。方法:采用Western blotting法检测70例声门上型喉癌组织原发灶、60例癌旁正常喉黏膜组织和44例颈部淋巴结转移灶中BRMS1蛋白的表达情况;甲基化特异聚合酶链反应(MSP)法检测上述组织中的BRMS1基因启动子区域甲基化情况,探讨BRMS1基因启动子甲基化与其基因表达的相关性;分析BRMS1蛋白表达及BRMS1基因启动子甲基化情况与患者的临床分期、病理分级、颈部淋巴结转移等方面的相关分析。结果:Western blotting检测发现声门上型喉癌原发灶、癌旁正常喉黏膜组织和颈部淋巴结转移灶均有BRMS1蛋白表达,在癌组织及转移淋巴结中BRMS1蛋白表达下调(P<0.05)。MSP法检测发现BRMS1基因启动子区甲基化,在BRMS1蛋白低表达患者的原发灶中检测到34例BRMS1基因启动子区甲基化,44例BRMS1蛋白低表达的颈部淋巴结转移灶中检测到32例BRMS1基因启动子区甲基化,60例癌旁正常喉黏膜组织中均未检测到BRMS1基因启动子区甲基化,统计学分析结果表明在声门上型喉癌中BRMS1基因启动子甲基化与其基因表达下调密切相关(rs=0.66,P<0.05)。结论:声门上型喉癌组织中BRMS1蛋白表达下调。BRMS1蛋白表达下调与声门上型喉癌的P-TNM分期、病理分化程度和颈部淋巴结转移密切相关。BRMS1基因启动子甲基化与声门上型喉癌组织中BRMS1基因表达下调相关,也可能是声门上型喉癌组织中BRMS1基因表达下调的原因之一。     

声门上喉癌MMP-2和E-cadherin的表达与颈部淋巴结转移的相关性研究

目的:探讨MMP-2、E-cadherin在喉癌组织中的表达及其与喉癌颈部淋巴结转移之间的关系。方法:应用免疫组织化学SP法检测10例正常喉黏膜和48例原发性声门上喉癌组织中MMP-2和E-cadherin的表达。结果:MMP-2在声门上喉癌组织中的表达明显高于正常喉黏膜组织中的表达;淋巴结转移组明显高于无淋巴结转移组(P<0.05);E-cadherin在正常喉黏膜组织中的表达明显高于在声门上喉癌组织中的表达;在淋巴结转移组明显低于无淋巴结转移组(P<0.05)。MMP-2和E-cadherin在声门上喉癌组织中的表达呈负相关(r=-0.41)。分别用MMP-2( )、E-cadherin(-)及MMP-2( )与E-cadherin(-)联合来预测喉癌颈部淋巴结转移,MMP-2( )的敏感性最高(91.7%),特异性(58.3%)和阳性预测值(68.8%)最低。MMP-2( )与E-cadherin(-)联合的敏感性最低(79.2%),特异性(95.8%)和阳性预测值(95.0%)最高。E-cadherin(-)的各项指标介于两者之间。结论:MMP-2和E-cadherin蛋白的表达可以作为判断声门上喉癌淋巴结转移的有效指标,联合应用MMP-2和E-cadherin蛋白的检测能够提高判断声门上喉癌淋巴结转移的准确率,对于声门上喉癌的手术治疗具有指导意义。     

葡萄糖转运蛋白1在人喉鳞状细胞癌中的表达及意义

目的:观察葡萄糖转运蛋白1(GLUT1)在人喉鳞状细胞癌中的表达及其与临床病理学的关系.方法:应用免疫组织化学的方法以及RT-PCR法检测57例喉鳞状细胞癌患者的肿瘤组织、癌旁喉组织以及远离肿瘤的正常喉组织中GLUT1的蛋白和mRNA的表达,并结合喉癌患者的临床病理特征进行分析.结果:①免疫组织化学:GLUT1在喉癌组织中的表达高于癌旁喉组织和正常喉组织(P<0.01);在低分化喉癌中的表达高于高分化喉癌(P<0.05);Ⅲ期+Ⅳ期喉癌较Ⅰ期+Ⅱ期喉癌有高表达GLUT1的趋势(P<0.01);有淋巴转移的喉癌的表达高于无淋巴转移者(P<0.05);在直径≥3 cm的肿瘤中的表达高于直径＜3cm者(P<0.05).②RT-PCR结果:GLUT1在喉癌组织中的表达高于癌旁喉组织和正常喉组织(P<0.01);在低分化喉癌中的表达高于中分化和高分化喉癌(P<0.05);Ⅲ期+Ⅳ期喉癌较Ⅰ期+Ⅱ期喉癌有高表达GLUT1的趋势(P<0.05);有淋巴转移的喉癌的表达高于无淋巴转移者(P<0.05);在直径≥3 cm的肿瘤中的表达高于直径＜3 cm者(P<0.05).结论:GLUT1与喉癌发生、发展、分化、淋巴转移和转归等密切相关,可以作为喉癌的诊断、治疗和预后指标之一.     

单层上皮细胞角蛋白在声门上型喉癌中的表达

目的 探讨角蛋白(cytokeratin,CK)19,CK18在声门上型喉癌中的表达及其临床意义。方法 用免疫组化法观察60例声门上型喉癌术后标本CK19,CK18的表达。结果①60例声门上型喉癌组CK19表达阳性53例,阳性率88.3％,而CK18呈阴性表达;②60例声门上型喉癌CK19表达与病理分级有关:中分化组与低分化组(P=0.019),高分化组与低分化组(P=0.003)之间的差异显著,而与TNM分期无关(P=0.186);③60例声门上型喉癌CK19表达在有淋巴结转移组明显高于无淋巴结转移组(P=0.019);④60例声门上型喉癌CK19表达与生存时间无关(P=0.438)。结论60例声门上型喉癌CK19表达与病理分级及淋巴结转移有关,而与TNM分期及生存时间无关。     

Stathmin基因在喉鳞状细胞癌中的表达及临床意义

目的 观察stathmin基因和蛋白质在喉鳞状细胞癌(简称鳞癌)中的表达情况,探讨stathmin基因与喉鳞癌生物学行为的关系及临床意义,进一步认识喉鳞癌发生和发展的分子机制.方法选取2005年3月至2006年4月的38例喉鳞癌患者,术中从肿瘤中心部位取癌组织(实验组),在肿瘤边缘外1.0cm部位取癌旁正常组织(对照组).应用半定量逆转录-聚合酶链反应(RT-PCR)分析38例患者的喉鳞癌组织和癌旁正常组织中stathmin基因mRNA的表达水平,冰冻切片免疫组织化学方法检测喉鳞癌组织和癌旁正常组织中stathmin蛋白的表达情况.结果 RT-PCR结果显示,stathmin基因mRNA在38例喉癌患者的喉癌组织和癌旁正常组织均呈阳性表达;经半定量分析,stathmin mRNA在喉癌组织中的表达水平明显高于在癌旁正常组织的表达水平(t=9.655,P＜0.05).免疫组织化学发现,stathmin蛋白在26例(26/38,68.4%)患者的喉癌组织呈阳性表达,在13例(13/38,34.2%)患者的癌旁正常组织呈弱阳性表达;stathmin蛋白在喉癌组织中的阳性表达率明显高于在癌旁正常组织的阳性表达率(x2=8.901,P＜0.05).同时发现,stathmin mRNA的表达水平和stathmin蛋白的阳性表达率在Ⅲ期和Ⅳ期喉癌组明显高于Ⅰ期和Ⅱ期病例组(t=6.284,x2=5.810,P＜0.05),有颈部淋巴转移组明显高于无转移组(t=9.350,x2=6.923,P＜0.05).结论 stathmin基因和蛋白在喉鳞癌中的表达明显高于癌旁正常组织,在中晚期喉鳞癌中的表达明显高于早期喉鳞癌,并且与颈淋巴转移有关.stathmin基因与喉鳞癌的发生和发展均有密切关系,并可能与喉癌的预后有关.     

声门上型喉癌组织中肿瘤相关巨噬细胞浸润与微淋巴管生成关系

目的 研究声门上型喉肿瘤癌内及癌周肿瘤相关巨噬细胞(TAM)计数与微淋巴管生成的关系。方法 通过免疫组化法测定84例声门上型喉癌癌内及癌周标本微淋巴管密度（LMVD)及TAM的表达,并分析癌内及癌周LMVD、TAM计数与声门上型喉癌临床病理学因素及生存率的关系。结果 TAM浸润与肿瘤微淋巴管生成呈正相关,癌内(r=0.253, P=0.02),癌周(r=0.270, P=0.013)。癌内TAM浸润随肿瘤T分期上升而增加,癌内TAM浸润越多肿瘤预后越差,淋巴结转移组的癌周TAMs显著高于淋巴结无转移组,发生远处转移组的癌内及癌周LMVD显著高于未发生远处转移组,癌周LMVD越高肿瘤预后越差。Kaplan-Meier生存分析显示癌内高密度TAM及高密度微淋巴管组5年生存率(47.6% )显著低于低密度组(86.4%）,癌周高密度TAM及高密度微淋巴管组5年生存率(50.7% )显著低于低密度组(81.0%)(P＜0.05)。结论 TAM和微淋巴管生成与声门上型喉癌转移和不良预后密切相关。     

细胞外基质抗原在声门上型喉鳞癌中表达的意义

目的：探讨细胞外基质（ECM）抗原的表达及其在声门上型喉鳞癌中的屏障意义。方法：分别应用抗Ⅳ型胶原纤维（CTⅣ）单克隆抗体、抗层粘连蛋白（LN）单克隆抗体、抗纤维连接蛋白（FN）单克隆抗体以链霉素亲生物素－过氧化酶免疫组化法观察这3种抗原在声门上型喉鳞癌中的表达分布情况，以评价ECM包绕癌巢的完整性与肿瘤细胞分化程度、浸润方式及颈淋巴结转移的关系。结果：在低分化和肿瘤弥散浸润的喉鳞癌组织中，3种抗原表达缺人率明显高于分化良好及肿瘤边界良好的组织（P＜0．01）。3种抗原表达缺失者发生颈淋巴结转移率高于表达完整者，二者之间有较强相关性（P＜0．01）。结论：ECM 3种抗原表达的完整性可以用来评价声门上型喉鳞癌细胞分化程度及喉鳞癌组织浸润能力，也可作为预测声门上型喉鳞癌发生颈淋巴结转移的重要参数之一。     

Temporal bone pathological study on maxillary sinus carcinoma with bilateral temporal bone metastasis

We report a case in which metastasis occurred from a left-side maxillary carcinoma to bilateral temporal bones through different routes, manifested by rapidly progressing left-side mixed hearing loss, left-side vestibular dysfunction, and serous otitis media. Later the left-side hearing threshold became severely elevated, suggesting profound sensory hearing loss. Histopathology of the temporal bones revealed that the side with the lesion was severely damaged by tumor through direct and hematogenous metastasis. On the contralateral side, it showed four findings: (i) sparse and separate tumor invasion of the petrous bone, the mastoid cavity, and the facial canal (hematogenous spread); (ii) tumor involvement in the lower part of the cochlear aqueduct without invasion of the internal acoustic canal or cochlea, implying early meningeal carcinomatosis; (iii) vascular stria atrophy, spiral ganglion diminution, and well preserved hair cells; and (iv) diffuse effusion in the middle ear and mastoid cavity. Our observations revealed that tumor cells dispersed to the same side through different routes, whereas early metastasis to the contralateral side was mainly through hematogenous and subarachnoid spread.     

Nasal tip metastasis: an unusual site and mode of spread in anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is the most aggressive and lethal form of thyroid malignancy which is difficult to treat. At the time of diagnosis, majority of patients have distant metastases most commonly in lung, bone, and liver. However nasal tip metastasis is not reported in literature. Implantation of malignant cells on nasal tip is also unknown. We hereby report an interesting and unusual mechanism for nasal tip metastasis in a patient with ATC.     

Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence. STUDY DESIGN: Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center. METHODS: Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality. RESULTS: Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls. CONCLUSIONS: Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.     

Expression of CC-chemokine receptor 7 (CCR7) and CXC-chemokine receptor 4 (CXCR4) in head and neck squamous cell carcinoma

Objectives

We tried to clarify the correlation of the expression of CCR7 and CXCR4 with lymph node and distant metastasis.

Materials and methods

We examined expression of CCR7 and CXCR4 in 9 HNSCC cell lines and 25 HNSCC tissues by semi-quantitative RT-PCR and immunohistochemistry study. We examined the expression levels of CCR7 and CXCR4 in undifferentiated and differentiated human normal keratinocyte.

Results

All cell lines expressed CCR7 mRNA, and three expressed CXCR4 mRNA. CCR7 and CXCR4 mRNAs were significantly higher in HNSCC tissues than in non-neoplastic tissues (p < 0.05, respectively) and correlated with lymph node metastasis (p < 0.05, respectively). The level of CXCR4 mRNA also correlated with distant metastasis (p < 0.05). Immunohistochemistry demonstrated localization of CCR7 and CXCR4 to carcinoma cells and lymphocytes and immunohistochemical staining scores of CCR7 and CXCR4 also showed similar correlation to lymph node and distant metastasis with CCR7 and CXCR4 mRNA levels. The level of CCR7 mRNA was significantly higher in poorly and moderately differentiated than in well-differentiated HNSCC (p < 0.05). The level of CCR7 mRNA in undifferentiated keratinocyte was significantly higher than that in differentiated keratinocyte.

Conclusion

The expression of CCR7 in HNSCC increases by dedifferentiation and plays an important role in lymph node metastasis of HNSCC and CXCR4 plays an important role in lymph node metastasis as well as distant metastasis.     

Rare case of orbital tumor

Most common malignancy involving orbit is secondary deposits. Orbital metastasis from thyroid malignancy is rare (3.6%) and is usually from follicular and medullary carcinoma thyroid. Here we are presenting the case report of a lady who presented with loss of vision and on evaluation was found to have orbital metastasis from papillary carcinoma thyroid.     

Organ and Voice Preservation in Advanced Laryngeal Cancer

Papillary or follicular microcarcinoma of the thyroid comprises 10–20% of all thyroid malignancies. Most of these diseases exhibit slow progression and have a favorable prognosis. Distant metastasis caused by thyroid microcarcinoma is uncommon, and is usually found in the lung or bone. Thyroid microcarcinoma with metastasis to the kidney has not previously been reported. Clinically detectable well-differentiated metastatic thyroid carcinoma to the kidney is rare, and only 16 cases have been reported. Herein we describe a case of metastatic papillary thyroid microcarcinoma to the kidney in a patient with a pelvic fracture and pulmonary metastasis. The patient underwent a total thyroidectomy, radiotherapy, ablation treatment with ¹³¹I and thyroxine suppressive therapy. In conclusion, microcarcinoma cannot be ignored. Although uncommon, metastases may arise.     

鼻咽癌细胞表面糖蛋白结构与转移倾向关系的研究

为研究鼻咽癌细胞表面糖蛋白结构的改变与其转移间的关系，测定了15例正常鼻粘膜和102例鼻咽癌（84例原发性癌和18例转移淋巴结）细胞的花生凝集素（peanutagglutinin）受体、荆豆凝集素（ulexeuropeans）受体和刀豆凝集素（concanavalinensifomisagglutinin）受体的改变。结果发现大多数（91．6％）鼻咽癌细胞的花生凝集素受体阳性，其与癌细胞的组织类型、细胞分化程度和转移无关。转移鼻咽癌细胞的荆豆凝集素受体明显增多，而刀豆凝集素受体明显减少。因此，鼻咽癌细胞荆豆凝集素受体增多和刀豆凝集素受体减少可能与其转移能力有关。