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。     

头颈部多原发癌

多原发癌(multiple primary carcinoma，MPC)由Billroth(1882)首先报道。近年来，随着诊断技术的日臻完善，治疗手段的不断更新，恶性肿瘤患者的存活率提高，加上严格的追踪随访，患者寿命延长，MPC的发病率也呈不断升高趋势。在肿瘤患者的远期并发症中，MPC最为严重，它不仅有较高的发病率，而且死亡率也较高。Brownson等     

头颈部多原发癌

多原发癌(multiple primary carcinoma,MPC)系指机体不同部位、器官同时或不同时发生2种或2种以上的原发性恶性肿瘤,包括交界肿瘤.     

头颈部多原发癌的致病危险因素

头颈部多原发癌发病率较高,是影响头颈部肿瘤患者生存期的重要因素之一.头颈部多原发癌的致病因素复杂,包括环境因素和患者自身因素等多方面.现将头颈部多原发癌的相关致病危险因素作一综述.     

头颈部多原发癌1例

患者,女,52岁.因"右鼻反复出血2个月余"入院.体检:右鼻腔见红色肿物,质韧,触之易出血,表面有破溃,凹凸不平.于2009年9月4日行鼻内镜下鼻腔肿物切除加鼻窦开放术(右).     

p53、p63、p73在鼻腔鼻窦恶性肿瘤中表达的临床意义

目的:探讨p53、p63、p73在鼻腔鼻窦恶性肿瘤中表达的临床意义及相关性。方法:用免疫组织化学方法检测67例鼻腔鼻窦恶性肿瘤、36例癌旁组织和36例鼻腔鼻窦的非癌组织中p53、p63和p73的表达。结果:p53、p63在鼻腔鼻窦恶性肿瘤中的阳性表达率明显高于癌旁和非癌组织(均P<0.01),p53与p63在鼻腔鼻窦恶性肿瘤中的表达存在正相关(P<0.01);p73在鼻腔鼻窦恶性肿瘤、癌旁和非癌组织中的表达差异无统计学意义(P>0.05)。结论:p53与p63在鼻腔鼻窦恶性肿瘤的发生发展过程中可能存在相关性,是鼻腔鼻窦恶性肿瘤发生过程中的重要因素之一,而p73在鼻腔鼻窦恶性肿瘤的发生过程中可能不发挥作用。     

中耳胆脂瘤上皮PTEN基因的表达及意义

目的探讨PTEN基因在中耳胆脂瘤形成机制中的作用。方法应用免疫组化染色和逆转录聚合酶链反应(RT-PCR)方法检测32例中耳胆脂瘤组织和10例正常外耳道皮肤组织中PTEN的表达情况。结果中耳胆脂瘤组织和正常外耳道皮肤组织均有PTENmRNA和蛋白的表达,且两组间无统计学差异(P>0.05)。结论在胆脂瘤形成过程中,PTEN的作用更趋向于维持上皮细胞的正常生理状态,而不是发生基因异常导致细胞非正常增殖。     

G1细胞周期调控与头颈部多原发癌的关系

细胞周期调控障碍与人类肿瘤的发生、发展关系密切。近年 来随着头颈部肿瘤局控率的不断提高,头颈部多原发癌也日渐增多,其发生的分子生物学机制复杂多样。本文通过复习相关文献,就G1细胞周 期调控障碍与头颈部多原发癌发生、发展的研究进展情况作一回顾。     

头颈部多原发癌68例临床分析

目的 探讨头颈部多原发癌(MPC)的发病情况、临床特征及治疗预后。 方法 对2014年1月1日至2017年12月31日收治的68例MPC的临床资料进行回顾性分析,采用SPSS 21.0软件进行统计学分析。 结果 在福建医科大学附属第二医院耳鼻咽喉科同期收治的8758例患者中有恶性肿瘤648例,其中有68例多原发癌,占比为0.78%。自2014年至2017年多原发癌年占比依次为:0.72%、0.72%、0.77%、0.86%。多原发癌组中男61例、女7例,其男女比例较单原发癌组高(χ2=8.18, P=0.004)。二重癌62例、三重癌6例。同时性MPC 35例、异时性MPC 33例。44例患者既往有吸烟/饮酒史,男性吸烟饮酒事件明显高于女性(χ2=6.40, P=0.006)。下咽癌的多原发癌发病率(23.81%)最高,其次为口腔癌(14.71%)、喉癌(9.33%)。口腔癌、下咽癌和喉癌最常见的第二原发癌均为食管癌。有45例(66.18%)第二癌与首发癌间隔时间小于5年。22例患者曾行放化疗,有放化疗史的多原发癌患者中异时性更多见(χ2=18.64, P<0.001)。 结论 发生MPC概率最高的头颈部肿瘤依次为下咽癌、口腔癌、喉癌。头颈部MPC并发食管癌等上消化道肿瘤的可能性大,故对头颈部肿瘤患者,建议将电子胃镜检查列为常规的术前检查及术后定期的随访检查手段;应加强首发癌治疗后长期,尤其前5年的密切随访。放疗过程中要加强对靶器官外的组织器官的放射防护。     

中耳胆脂瘤上皮中Livin、p73的表达与其发生关系研究

目的 观察凋亡抑制蛋白家族成员Livin及p53基因家族成员p73在中耳胆脂瘤上皮的表达情况,探讨它们在胆脂瘤发病机制中的作用.方法 采用免疫组织化学技术SP法(streptavidin-perosidabe,链霉菌抗生物素蛋白-过氧化物酶连结法)检测30例胆脂瘤标本及16例外耳道正常皮肤组织中的Livin及p73的表达情况,并结合胆脂瘤对听小骨骨质破坏程度,采用SPSS 10.0软件包进行统计学分析.结果 Livin表达于细胞核及部分细胞质,而D73表达于胞浆,上述两指标在中耳胆脂瘤中的阳性表达率分别为76.7%、40%,Livin在胆脂瘤上皮中的表达高于外耳道正常皮肤(P<0.05),而p73在胆脂瘤及外耳道皮肤中的表达差异无显著性(P>0.05),听小骨骨质破坏程度与上述指标的表达差异无统计学意义(P>0.05).结论 Livin在中耳胆脂瘤的异常表达可能在胆脂瘤的发生、发展过程中起相应作用,可能参与胆脂瘤上皮的凋亡调控过程,而p73在中耳胆脂瘤的发生和发展中的作用尚难确定.     

p53家族新成员p63,p73与头颈部肿瘤

p53是研究较为广泛的抑癌基因，随着p53的广泛和深入研究，其家族成员p63与p73陆续被发现后，即成为人们关注的热点。本文就p63、p73的表达类型、结构和功能及其与头颈部肿瘤的相关性作一综述。     

p73和PCNA的表达与喉鳞状细胞癌的预后

目的：探讨喉鳞状细胞癌（LSCC）中p73、增殖细胞核抗原（PCNA）基因的表达与患者临床、病理参数和预后的关系。方法：采用免疫组织化学SABC技术检测65例LSCC组织及23例癌旁组织中p73、PCNA基因的表达情况。结果：p73、PCNA蛋自在65例LSCC组织中的表达水平较23例癌旁组织明显增强（均P〈0．05）。65例LSCC组织中,p73蛋自在TNM分期Ⅲ～Ⅳ期、远处转移及复发患者中的表达水平较Ⅰ～Ⅱ期、无转移及初发患者表达增强（P〈O．05）。PCNA蛋自在TNM分期Ⅲ～Ⅳ期患者、低分化癌、复发患者和有颈淋巴结转移及远处转移患者中的表达水平较Ⅰ～Ⅱ期、高中分化、初发患者和无转移患者中的表达增强（P〈O,05）。PCNA蛋白的表达与患者预后明显相关。经Cox比例风险模型进行分析,PCNA表达是患者预后不良的重要指标（其相对危险度RR=2.43,P〈0．05）。LSCC组织中p73、PCNA的基因表达存在正相关性（P〈0、05）。结论：p73蛋自在LSCC的发生、发展过程中可能扮演了癌基因的角色。PCNA蛋白的表达与LSCC的危险性存在密切关系,可作为判断LSCC患者预后的重要指标。LSCC中p73、PCNA的表达存在正相关关系。     

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.     

Statistical survey of multiple primary cancers of the head and neck]

The incidence and factors associated with multiple primary cancer were surveyed and analyzed from April 1978 through December 1990 in our clinic. Fifty-nine cases with multiple primary cancers were selected for study from among 579 cases with malignant head and neck region tumors. The cancers involved the larynx in 17 cases (8.4%), oral cavity in 14 (19.4%), oropharynx in 13 (41.9%), hypopharynx in 7 (8.0%) and nasal cavity or paranasal sinus in 7 (8.0%). Twenty-one cases (35.6%) arose synchronously within one year. From our observations, heavy drinking and smoking were most strongly suspected to be risk factors for induction of malignancy. Most multiple primary cancers in the head and neck region were observed to coexistent in a "so called multicentric zone" consisting of the oral area, pharyngeal area, larynx, esophagus, stomach, and tracheobronchial tree. To avoid overlooking concealed cancer in the multicentric zone, upper gastro-intestinal endoscopy, bronchial endoscopy, chest X-ray and sputum examination should be performed for screening of patients with head and neck malignancies.     

Immunoglobulin allotypes in head and neck cancer patients with multiple primary cancers

Immunoglobulin allotypes G1m, G2m, G3m, A2m and Km were determined in patients with a single head and neck cancer and in head and neck cancer patients with multiple primary tumours. Frequencies were compared with those of healthy controls. In all 39 patients with multiple primary tumours studied, Km(1) was absent vs. 82% and 75% absence in healthy controls and patients with a single head and neck cancer, respectively. This difference is highly significant. We conclude that head and neck cancer patients lacking the Km(1) are susceptible to the development of new cancers, and therefore should be screened thoroughly for more tumours.     

Multiple primary cancers of the head and neck

Multiple primary cancers of the head and neck are not always rare. We have experienced 30 cases of multiple primary cancers in the Department of Otolaryngology, Ehime University School of Medicine from 1976 to 1989. The incidence ranged from 3.6% to 8.9% with flexible criteria. The minimum was 14 of 393 cases of all index cancers, strictly conformed with Warren's definition. The maximum was 29 of 327 cases of index cancers on the mucosal surfaces, including a combination of both head and neck cancers. In view of organic specificity of the index cancers, the incidence was high in the larynx and oral cavity, low in the nasopharynx and maxillary sinus. The concept of "multicentric cancerization" was verified by the result that 60% of the additional cancers were head and neck, esophagus and lung. During following-up studies of oropharyngeal, hypopharyngeal and laryngeal cancers, we have to examine the esophagus periodically due to high risk of occurrence of cancer. To compare the data of multiple primary cancers of the head and neck between institutions, adequate and detailed criteria should be established.