鼻腔鼻窦恶性肿瘤p53基因突变的检测及临床意义

应用聚合酶链反应－单链构象多态性分析方法，检测２１例鼻腔鼻窦恶性肿瘤新鲜及石蜡包埋组织中，Ｐ５３基因第６外显子的突变率发现Ｐ５３基因第６外显子突变１４例，突变率为６７％。其Ⅰ－Ⅳ期的分布分别为３３％；其分化程度分布为３３％，６７％，８９％；有淋巴结转移者为１００％，无转移为５９％。     

鼻腔及鼻窦恶性肿瘤中p53基因突变的检测

目的探讨p53基因突变在鼻腔、鼻窦恶性肿瘤发生发展中的突变状况及其意义.方法用聚合酶反应-单链构象多态性分析(PCR-SSCP)方法测定36例鼻腔、鼻窦恶性肿瘤中p53基因4个突变热点,第5～8外显子.结果鼻腔及鼻窦恶性肿瘤p53基因突变率为38.9%(14/36)与正常鼻粘膜组织相比,与慢性鼻炎粘膜组织相比有显著性差异(χ2=11.874,P<0.05).淋巴结转移阳性组突变率为66.7%(10/15),阴性组突变率为19%(4/21),两者相比有显著性差异(χ2=10.219,P<0.05)但与临床分期、病理分型无关.结论 p53基因突变可能在鼻腔、鼻窦恶性肿瘤发生发展过程中是一个重要的分子事件,淋巴结转移和晚期有上升趋势.     

鼻腔鼻窦非上皮性恶性肿瘤

目的 为了加强对鼻腔鼻窦少见的非上皮性恶性肿瘤的认识,对其临床特征、病理学特征进行讨论。方法 采用ＨＥ染色及免疫组化明确病理诊断后,进行治疗并随访。结果 经１～８年随访观察,存活２～８年１０例,其中恶性黑色素瘤３例;非霍奇金淋巴瘤、恶性纤维组织细胞瘤各２例;浆细胞瘤、横纹肌肉瘤和神经源性肉瘤各１例。结论 这类肿瘤生长速度快,恶性程度高,易发生转移及侵犯周围器官,难于手术彻底切除,５年生存率低,免疫     

延边地区113例鼻腔鼻窦恶性肿瘤的临床病理分析

目的 探讨延边地区鼻腔鼻窦恶性肿瘤的临床病理特征,为防治本地区鼻腔鼻窦恶性肿瘤提供科学依据.方法 回顾性分析我院1980-2007年经病理确诊的鼻腔鼻窦恶性肿瘤113例患者的临床病理资料.结果 本组113例中鳞癌占44.2%、淋巴瘤为28.3%和涎腺型癌占14.2%;朝、汉族中鳞癌各为38.3%和50.9%、恶性淋巴瘤为30.0%和26.4%、涎腺型癌为15.0%和13.2%;朝、汉族男性鳞癌发病平均年龄各为51.9和55.2岁、淋巴瘤为46.5和55.0岁(T=2.436,P<0.05);朝鲜族女性中鳞癌较多,汉族女性中恶性淋巴瘤较多.结论 延边地区鼻腔鼻窦恶性肿瘤中鳞癌最多,其次是恶性淋巴瘤和涎腺型癌,两个民族、不同性别中肿瘤的类型和平均年龄有差异,朝鲜族男性恶性淋巴瘤发病平均年龄比汉族男性明显年轻.     

鼻腔及鼻窦恶性肿瘤

鼻腔及鼻窦恶性肿瘤较为少见,据统计约占全身恶性肿瘤的0．5％,在头颈恶性肿瘤中〈3％,在日本约占头颈部癌的23％,美国年发病率为0．5-1／100000,常发生于50-60岁老年人,男女比例约为2：1。     

喉癌中maspin与p53表达的相关性

目的 观察喉癌中maspin和p53蛋白的表达,探讨maspin和p53在喉癌发生、发展中的作用。方法 采用免疫组化法检测78例喉鳞癌组织中maspin和p53蛋白。结果 在喉癌中maspin阳性表达率为55.1%(43/78),maspin表达下降与病理分化程度低、淋巴结转移有关。p53阳性表达率为58.9%(46/78)。在maspin阳性表达的43例喉癌中,p53阳性表达率为79.1%,maspin阴性表达的喉癌中,p53阳性表达率为34.3%,差异有统计学意义(P<0.05)。Spearman等级相关分析显示,maspin在喉癌组织中的表达与p53呈负相关性,有统计学意义(rs=-0.381, P=0.006)。结论 maspin在喉癌的发生发展中起一定抑制作用。喉癌中maspin表达与p53表达呈负相关,maspin可能是p53的效应基因。     

p21、p73及PTEN在头颈部多原发癌中的表达及意义

目的:探讨p21、p73与PTEN在头颈部多原发癌组织中的表达与意义。方法:采用 免疫组织化学方法对30例头颈部多原发癌患者的42份标本、42例头颈部单发癌及30例来源于头颈部的正常上皮组织标本中p21、p73与PTEN蛋白表达进行检测,并将检测结果作统计学分析。结果:p21、p73与PTEN蛋白在头颈部多原发癌组织中阳性表达率分别为69.05％、57.14％和71.43％;在单原发癌组阳性表达率分别为76.19％、40.48％和76.19％;在正常上皮组织中阳性表达率分别为96.66％、13.33％和100.00％。在多原发癌及单发癌组织中p21与PTEN蛋白失表达率以及p73蛋白过表达率均显著高于正常上皮组织（P＜0.05）;三个指标在多原发癌与单发癌组织中的表达差异均无统计学意义。结论:p21与PTEN蛋白失表达以及p73蛋白表达上调,参与头颈部多原发癌和单发癌的形成机制,但还不能认为其在头颈部多原发癌与单发癌形成中的作用有差别。     

p53蛋白在喉鳞癌及癌旁组织中表达的研究

应用抗ｐ５３单克隆抗休琢ＬＳＡＢ免疫组织化学染色法检测喉鳞癌，喉癌旁组织及声带息肉ｐ５３蛋白的表达。结果显示：２５例喉鳞癌呈阳性反应，４例距肿瘤边缘〈０．５ｃｍ的喉癌旁组织呈弱阳以应，２０例距肿瘤边缘〉２ｃｍ的喉癌旁组织及１６例声带息肉均为阴性。     

Differential expression of p53, p63 and p73 proteins in human buccal squamous‐cell carcinomas

Abnormalities in the p53 gene are regarded as the most consistent of the genetic abnormalities in oral squamous‐cell carcinoma. Two new members of the p53 gene family, p73 and p63, have recently been identified, with the three sharing considerable sequence homology at the acidic N‐terminal transactivation, central DNA‐binding and C‐terminal oligomerization domains, indicating possible functional and biological interactions. The differential expression of p73, p63 and p53 genes in human oral squamous‐cell carcinoma does not yet appear to be completely understood, however. In this study, therefore, immunohistochemical analysis of protein expression was performed for 40 samples of well‐differentiated human buccal squamous‐cell carcinomas, with 10 specimens of normal buccal mucosa employed as controls. Differential expressions of p63, p73 and p53 proteins in the carcinoma samples were: p63+/p73+/p53 + (n = 28; 70%); p63+/p73+/p53– (n = 4; 10%); p63+/p73–/p53– (n = 8; 20%), respectively; and p63+/p73+/p53– for normal mucosa (n = 10; 100%). A significant correlation between p53, p63 and p73 immunoexpression was demonstrated for the buccal squamous‐cell carcinoma samples (P < 0.0001; Fisher's exact test). Significance was not achieved for the correlation between p73 and p53 immunoexpression and clinicopathological parameters for buccal carcinomas (P > 0.05; Fisher's exact test). Our results indicate that both p73 and p63 may be involved in the development of human buccal squamous‐cell carcinoma, perhaps in concert with p53.     

P63蛋白在甲状腺肿瘤中表达的意义

目的:探讨p63蛋白在甲状腺腺瘤、甲状腺乳头状癌、甲状腺滤泡癌、鳞状细胞癌和甲状腺髓样癌中的表达意义,探索这些甲状腺疾病的可能起源,以及这些疾病病因之间有无联系。方法:运用免疫荧光法检测10例甲状腺腺瘤、25例甲状腺乳头状癌、4例甲状腺滤泡状癌、2例髓样癌和2例甲状腺鳞状细胞癌中p63的表达。结果:p63在甲状腺腺瘤、甲状腺乳头状癌、甲状腺滤泡癌、甲状腺鳞状细胞癌和甲状腺髓样癌中均有表达。p63在鳞状细胞癌和髓样癌中表达最高,在甲状腺乳头状癌中其表达与患者年龄、性别、肿块位置、肿块大小和有无转移无明显相关性。结论:①甲状腺组织内存在p63阳性标记的干细胞;②甲状腺乳头状癌、滤泡癌、鳞状细胞癌等可能起源相似。干细胞是多功能细胞,向不同方向分化,形成不同疾病;③p63在甲状腺鳞状细胞癌和髓样癌中表达最高,说明在鳞状细胞癌中残留干细胞较多,与肿瘤的生物学特性一致。     

喉鳞状细胞癌组织中p63表达的临床意义

目的：探讨p63基因在喉鳞状细胞癌中的表达及其临床意义。方法：用免疫组织化学法检测63例喉鳞状细胞癌（喉癌组）及其45例癌旁组织（癌旁组）、24例转移淋巴结（转移淋巴结组）、40例未转移淋巴结（未转移淋巴结组）及25例喉非癌组织（非喉癌组）中p63基因的表达。结果：p63基因在喉鳞状细胞癌组织中均为细胞核阳性表达,喉癌组及转移淋巴结组的中、强阳性率为95．2％（60／63）和83．3％（20／24）;癌旁组及未转移淋巴结组中无中、强阳性表达;非喉癌组中1例乳头状瘤为弱阳性表达,其余均为上皮细胞或基底细胞核弱阳性表达。结论：p63可作为喉鳞状细胞癌有特异性的标记物,对喉鳞状细胞癌的早期诊断和鉴别诊断有重要意义。p63可能主动参与了调控喉鳞状细胞癌的发生过程,但在喉鳞状细胞癌的发展过程中处于被激活状态,可能在发展过程中发挥负反馈的作用。     

Inhibition of epidermal growth factor receptor signaling decreases p63 expression in head and neck squamous carcinoma cells

OBJECTIVES/HYPOTHESIS: Both the epidermal growth factor receptor (EGFR) and the p53 homologue p63 are overexpressed in a significant number of cases of head and neck squamous cell carcinoma (HNSCC). Epidermal growth factor receptor and p63 both possess oncogenic properties, including the potential to increase cell proliferation and antagonize apoptosis. ZD1839 ("Iressa") is an adenosine triphosphate-competitive inhibitor specific to the EGFR tyrosine kinase currently under evaluation as a chemotherapeutic agent in HNSCC. The objective was to investigate whether p63 expression is decreased after treatment of HNSCC cells with ZD1839. Downregulation of p63 by ZD1839 would identify a potential molecular relationship between EGFR signaling and p63 and could provide insight into the mechanism of action of ZD1839. STUDY DESIGN: In vitro examination of p63 expression after ZD1839 treatment. METHODS: A human HNSCC cell line, SCC-012, was treated with varying doses of ZD1839. p63 protein and messenger RNA levels were analyzed by Western and Northern blot analyses. The effect of ZD1839 on SCC-012 cell cycle was analyzed by flow cytometric analysis. RESULTS: In SCC-012 cells there was a dose-dependent decrease in p63 protein and messenger RNA levels over the course of ZD1839 treatment. Levels of phosphorylated MAPK decreased and p27KIP-1 levels increased after ZD1839 treatment. ZD1839 treatment induced a twofold increase in G1-phase cells and a 3.5-fold decrease in S-phase cells consistent with growth arrest. CONCLUSION: ZD1839 downregulates p63 expression at the messenger RNA level, suggesting that p63 is a downstream target of EGFR signaling.     

Increased expression of p63 and survivin in cholesteatomas

Conclusion. This study showed increased expression of p63 and survivin in cholesteatoma. Our finding indicates a putative role of p63 and survivin in the development of certain cholesteatomas. Objectives. Keratinocytes in cholesteatoma demonstrate uncoordinated hyperproliferation, migration, and invasion properties. p63 is a p53 homologue and a marker expressed in replicating keratinocytes. Survivin is an inhibitor of apoptosis protein that is abundantly expressed in most solid and hematologic malignancies. The purpose of this study was to investigate the differential expression of p63 and survivin in human middle ear cholesteatoma epithelium. Materials and methods. The expression levels of p63 and survivin protein were examined by immunohistochemical analysis of 40 cholesteatomas and 5 skin tissues obtained from patients during ear surgery. Results. Expression of p63 protein was diffusely observed in entire samples of cholesteatoma, especially in acquired cholesteatoma, compared with the control group. Congenital cholesteatoma showed variable p63 reactivity in a basal cell-like pattern. Primary and recurrent cholesteatomas showed no significant difference in p63 expression. Survivin was detected in 31 of 40 cholesteatoma samples. Acquired cholesteatomas showed especially increased survivin expression compared with congenital cases. The expression of p63 was correlated with survivin expression.     

p21、p73和PTEN蛋白表达联合检测在头颈部多原发癌诊断中的价值

目的：探讨联合检测p21、p73及PFEN的表达状况在头颈部多原发癌诊断与鉴别诊断的意义。方法：应用免疫组织化学方法检测12例头颈部多原发癌组织中的p21、p73和PFEN蛋白表达,比较先证癌与第二癌间指标的表达状况。结果：12例头颈部多原发癌的先证癌与第二癌组织中p21、p73或PFEN单一指标表达结果不一致的分别为7例、3例、8例;联合对比p21和p73、p21和PIEN或p73和PFEN两指标表达结果存在不一致的分别为8例、9例、9例;联合对比p21、p73及PTEN三指标表达结果存在不一致的为10例。结论：应用免疫组化方法联合检测p21、p73及PFEN蛋白表达可提高头颈部多原发癌诊断的敏感性。多种相关基因蛋白表达的联合检测可成为头颈部多原发癌,临床诊断与鉴别诊断的方法之一。     

Gleevec suppresses p63 expression in head and neck squamous cell carcinoma despite p63 activation by DNA-damaging agents

OBJECTIVES: The objectives of this study were to determine the effects of Gleevec on p63 expression in head and neck squamous cell carcinoma (HNSCC) cell lines and to investigate the role of Gleevec in regulating p63 stabilization under DNA-damaging conditions. METHODS: Immunohistochemical staining was performed to determine p63 expression in HNSCC tissue. Annexin V staining was used to assess the effects of p63 on early apoptosis. Immunoblotting was used to examine the effects of Gleevec on p63 protein levels in HNSCC cell lines in response to DNA damage. Immunofluorescence staining was performed to study the expression pattern of p63 and c-Abl. RESULTS: In HNSCC, p63 protein levels are induced by DNA-damaging agents, including ionizing radiation, doxorubicin, and ultraviolet light. We demonstrate that Gleevec reduces p63/DeltaNp63 expression in a dose-dependent manner in HNSCC and overrides the protein induction by DNA-damaging agents. Overexpression of c-Abl in the absence of Gleevec results in higher levels of p63 than those treated with Gleevec, implicating c-Abl kinase activity as a regulator of p63 protein stability. CONCLUSIONS: Gleevec downregulates p63/DeltaNp63 levels in HNSCC in a dose-dependent manner under both normal and DNA-damaging conditions. This downregulation can be explained by Gleevec's inhibition of c-Abl, which destabilizes p63. Based on our data, treating cancers with high expression of TAp63 with Gleevec may result in the unfavorable inhibition of a tumor suppressor, whereas downregulation of DeltaNp63 would be advantageous. Further development of antibodies that can discriminate between TAp63 and DeltaNp63 will be needed to determine the specific effects of Gleevec on p63 in HNSCC.