喉癌前病变100例分析

对１００例喉癌前病变进行临床及病理学分析。发现喉癌病变的发病和过度使用嗓音及长期大量吸烟有密切关系，其病理表现为上皮典型增生及轻、中、重度非典型增生（亦称异型）。扫描电观察到随喉粘膜上皮细胞异型程度的增加，细胞表面形状、大小、边级、细胞间连接等有显著不同。１００例中有２０例转为恶性。其中，慢性肥厚性喉炎的恶变率为１１．６％，喉角化症为１９５，喉乳头状瘤为３６。临床表现及病理均证明为喉息肉的病例也有     

MicroRNA-34c-5p在喉癌前病变组织中的特征性差异表达及临床病理分析

目的　探讨microRNA-34c-5p（miR-34c）在喉癌前病变组织中差异表达情况,并进行临床病理相关性分析。方法　按照2005年世界卫生组织（WHO）病理诊断标准,94例喉癌前病变分为轻度异型增生、中度异型增生、重度异型增生及原位癌;实时定量聚合酶链式反应（quantitative real-time polymerase chain reaction,qRTPCR） 方法检测94例喉癌前病变组织中miR-34c在各组间的差异表达情况,并结合临床资料及随访结果分析miR-34c与喉癌前病变病例临床因素的相关性。结果　94例喉癌前病变病例年龄37~86岁,平均58岁,男性85例（90.4%）,女性9例（9.6%）。轻度异型增生组20例（21.3%）,中度异型增生组23例（24.5%）,重度异型增生组26例（27.7%）,原位癌组25例（26.6%）。随喉癌前病变级别增高,miR-34c在喉癌前病变组织中呈上调表达趋势,总体组间存在统计学差异（F =10.182,P =0.00）,而在浸润性鳞状细胞癌组下降,甚至明显低于正常鳞状上皮组织的表达均值。临床病理分析显示饮酒病例中表达明显高于非饮酒病例,且miR-34c与喉癌前病变患者饮酒因素存在明显线性依存关系（r =0.31,P =0.03）。结论　MiR-34c在喉癌前病变组织中的上调表达趋势,可能为辅助喉癌前病变病理分级和早期喉癌诊断提供一定的分子病理参考价值,miR-34c的上调表达与喉癌前病变饮酒因素呈线性相关,对于指导喉癌前病变病例的临床管理可能具有重要临床意义。     

9例喉疣状癌和乳头状鳞状细胞癌的临床分析

目的：探讨喉疣状癌（VC）和乳头状鳞状细胞癌（PSCC）的临床、病理特点及鉴别诊断。方法：回顾性分析我院收治的4例喉VC及5例PSCC的临床资料,观察喉Vc及PSCC的临床及病理学特点。结果：4例喉VC均可见鳞状上皮高度增生,伴有角化珠形成,基底膜不受侵犯,肿瘤基质可见中至重度炎性浸润,未见颈部淋巴结转移,无局部复发,预后良好。5例喉PSCC均可见外生性恶性增殖并有血管纤维核心的鳞状细胞,细胞病理学表现与传统的鳞状细胞癌（SCC）基本一致,未见颈部淋巴结转移,预后较传统SCC好。结论：VC和PSCC两者在外观上较相似,但肿瘤细胞的分化、异型性,间质的炎性浸润,复发,局部转移,治疗及预后等方面存在差异,临床及病理医生需密切配合检查,以便鉴别诊断两类疾病。     

形态计量和DNA定量测定在鼻咽癌诊断中的价值

应用图像分析技术对７２例鼻咽部取材标本进行了１３项参数及ＤＮＡ定量测定。结果，在Ｉ～Ⅳ组间（Ｉ组正常鼻咽粘膜上皮，Ⅱ组单纯增生或化生，Ⅲ组异型增生或化生，Ⅳ组鼻咽癌），细胞形态参数及ＤＮＡ含量、倍体类型的百分比均值随细胞增生程度而逐渐递变。１３项参数均值进行多元逐步判别分析，优选出４项参数，建立判别函数，回代判别准确率为１００％。ＤＮＡ含量测定以倍体（ｐｌｏｉｄ）表示，认为细胞形态和ＤＮＡ定量分析是一种较为可靠的诊断方法，并提示鼻咽异型增生或化生属癌前病变。     

喉癌前病变恶变机理的探讨

选自北京同仁医院耳鼻咽喉科1992年5月～1994年6月收集的标本61例，其中喉癌前病变标本34例，利用免疫组化（P(53)、PCNA）及原位杂交技术，重点对不同病变阶段的10例慢性肥厚性喉炎、13例喉角化症和11例喉乳头状瘤（成人）进行检测，并与16例喉单纯息肉和11例喉原位癌标本进行了比较。分析了各种检测的阳性表达率在病变发展过程中的变化规律，对喉癌前病变的转归进行评估和预测。喉单纯息肉、喉癌前病变和原位癌三种病变中，P(53)蛋白的表达率分别是0％，35．29％和63.64％；PCNA指数分别是6．32％、26．16％和62．02％。在喉癌前病变和原位癌中，HPV(16.18)的阳性表达率分别是32．40％和63．63％。在癌前病变中重度非典型增生与轻、中度非典型增生P(53)和PCNA的阳性表达率有明显的差异（P＜0.05）。     

喉上皮增生性病变类型及HPV DNA亚型检测相关性研究

本文对４３例喉上皮非典型增生性病变及２４例喉鳞状细胞癌进行病理组织学观察，并分别应用Ｄｉｇ标记的ＨＰＶｇｂ／１１，１６，１８型ＤＮＡ，用原位杂交进行检测，其结果在轻度非典型增生１２例中原位杂交ＨＰＶ６ｂ／１１，１６，１８型检出率分别为１２／１２（１００％），２／１２（１６％），３／１２（２５％）；中度非典型增生１９例，检出率分别为１４／１９（７３％），８／１９（４２％），１４／１９（７３％）重度非     

喉癌及癌前病变等位基因不平衡性的相关研究

目的探讨喉鳞状细胞癌变过程中微卫星DNA等位基因不平衡性的特征及其意义。方法选取染色体3P、9P和17P上6个多态性微卫星位点D3S1234、D9S171、D9S1748、D9S162、INFA和D17S796,利用聚合酶链式反应一简单序列长度多态性一银染技术,对49例喉癌癌前病变和喉癌组织进行等位基因不平衡分析,统计杂合性缺失（10ssofheterozygosity,LOH）和微卫星不稳定性（microsatelliteinstability,MSI）的发生率及其与临床病理特征的相关性。结果6个微卫星标记物LOH和MSI发生率分别为：喉癌癌前病变中单纯过度增生为3．7％和14．8％,轻度不典型增生为10．8％和21．6％,重度不典型增生为26．0％和23．3％;喉鳞状细胞癌为38．7％和21．3％。其中LOH的总检出率在不同病理组间有统计学意义（X2=17．686,P=0．000）,而MSI的检出率统计学意义（X2=0．314,P〉0．05）。不同病理组间D9S171和D9S162单个位点LOH检出率有统计学意义（P=0．022,P=0．025）。在癌前病变早期MSI发生率高于LOH。结论等位基因不平衡可能参与喉癌发生发展,微卫星分析法为喉癌癌前病变的早期诊断提供新的途径。     

增殖细胞核抗原在喉上皮癌前病变中的表达及意义

用免疫组化技术对１１例喉上皮单纯性增生（ＳＨＥ），３２例非典型性增生（ＡＨＥ）及４２例喉鳞状细胞癌（ＬＳＣＣ）的增殖细胞核抗原（ＰＣＮＡ）表达进行了原位检测。结果表明；在ＳＨＥ、ＡＨＥ及ＬＳＣＣ中，ＰＣＮＡ指数分别为９．５７％、２７．３３％、６８．０５％，差异极有显著性意义（Ｐ＜０．００１）。在轻、中、重度ＡＨＥ中，ＰＣＮＡ指数分别为１３．７９％、３０．８４％、３９．９４％，差异有非常显著性意义（Ｐ＜０．０１）。提示ＰＣＮＡ表达程度与非典型性增生程度密切相关，是反映细胞增殖状态的生物标志，ＰＣＮＡ组化研究有助于认识喉癌前病变的本质，发展趋势及喉癌的早期诊断。     

喉上皮增生性病变中PCNA及c-erbB-2的表达及其临床意义

目的：研究ＰＣＮＡ及ｃ－ｅｒｂＢ－２在喉上皮增生性病变中的表达与增生程度的关系。方法：对１０例上皮单纯性增生、２６例异型增生及３０例喉鳞状细胞癌石蜡包埋标本,用免疫组化ＳＰ法检测其ＰＣＮＡ及ｃ－ｅｒｂＢ－２。结果：单纯性增生、异型增生和喉鳞癌间三者ＰＣＮＡ指数分别为６．６４％、２９．６３％及６２．６７％,差异有显著性意义（Ｐ〈０．０１）;单纯性增生病变与轻度异型增生间亦有显著性差异（Ｐ〈０．０１）     

咽喉反流及胃食管反流在喉癌前病变及喉癌发生中的作用

目的探讨咽喉反流及胃食管反流在喉癌前病变及喉癌发生中的作用。方法2004年4月-2009年5月北京大学人民医院耳鼻咽喉科就诊并手术切除经病理确诊为声带黏膜不典型增生,经患者同意行24小时双探头pH监测（简称监测）的患者12例,1例喉鳞状细胞癌（T1N0M0）患者。结果13例患者监测,咽喉部pH阳性7例（53．85％）,食管部pH阳性8例（61．53％）,两者均阳性6例（46．15％）,其中7例咽喉部阳性和8例食管部阳性的患者反流症状指数量表阳性均为5例,反流检查计分阳性均为6例。结论咽喉反流及胃食管反流可能是喉癌前病变和喉癌发生的危险因素之一。     

Application of Ljubljana classification in laryngeal precancerous lesions

The diagnosis and treatment of laryngeal premalignant lesions has been frustrated because of failure to adequately define the histologic changes that may help in prediction of irreversible neoplastic transformation. To assess the grading of laryngeal hyperplastic epithelial lesion it was used a Ljubljana classification of histologic changes. It was done a retrospective study of 104 laryngeal hyperplastic lesions biopsies that were classified according to the Ljubljana classification comprising benign spinous layer augmentation (simple hyperplasia), benign basal and parabasal layer augmentation (abnormal hyperplasia), alteration of epithelial cells towards malignancy (atypical hyperplasia) and carcinoma in situ. One hundred and four biopsies with preneoplastic changes were reevaluated and classified according to Ljubljana classification. It was found 42 cases (40.4%) which showed simple, 38 (36.5%) abnormal, 21 (20.2%) atypical hyperplasia and 3 (2.9%) carcinoma in situ. Three cases of atypical hyperplasia (2.9% of all investigated cases) and one of abnormal (0.96%) progressed to invasive carcinoma during the observation ranging from 5 to 9 years (median 8.1). None of the cases classified as simple hyperplasia showed progression to malignancy. The Ljubljana classification focuses on the important clinical decision involving benign looking hyperplastic lesion that do not require strict follow-up (simple and abnormal hyperplasia); and "risky" epithelium that require close follow-up with repeated histologic assessment to recognize any malignant progression (atypical hyperplasia); and carcinoma in situ that requires fast and complete treatment. We suggest that the Ljubljana classification may give a reliable assessment of laryngeal hyperplastic epithelial lesions and can help in monitoring all those patients.     

Laryngeal granuloma: characteristics of the covering epithelium

The purpose of the present study was to evaluate the biological behaviour of the marginal epithelium, that proliferates and eventually covers laryngeal granulomas, and to reveal the applicability of the recently re-introduced Ljubljana classification when reporting reactive epithelial hyperplastic lesions. A retrospective clinical and histomorphological analysis was performed on 149 laryngeal granuloma biopsies. Epithelial changes were classified according to the Ljubljana classification into normal epithelium; simple, abnormal, or atypical hyperplasia; and carcinoma in situ. Atrophic epithelium, not evaluated separately in the Ljubljana classification, was additionally assessed. Simple hyperplasia was found in 98 cases (65.8 per cent), abnormal hyperplasia in seven (4.7 per cent), atrophic epithelium in 24 (16.1 per cent), and normal squamous epithelium in 20 (13.4 per cent). Atypical hyperplasia and carcinoma in situ were not observed. The results of our study clearly showed that the proliferation of the covering epithelium mostly in the form of simple hyperplasia, is entirely reactive and therefore reversible. No epithelial hyperplastic lesions were found that were previously described to be associated with an increased risk of malignant alteration, namely atypical hyperplasia and carcinoma in situ. However, since an initial growth of an invasive malignant neoplasm might macroscopically imitate the appearance of laryngeal granuloma, a histological examination in all aetiological forms of laryngeal granulomas is required. By clearly discerning the benign nature of epithelial changes in laryngeal granulomas, the recently re-evaluated and further formulated Ljubljana classification may also influence the clinical handling of patients.     

Clinical applicability of the Ljubljana classification of epithelial hyperplastic laryngeal lesions

The diagnosis, prognosis, and choice of treatment of various laryngeal lesions depends almost entirely on the interpretation of changes in the covering epithelium. These abnormalities, referred to as epithelial hyperplastic laryngeal lesions, have been graded according to the Ljubljana classification into simple, abnormal and atypical (risky epithelium) hyperplasia and carcinoma in situ. The aim of this study was to evaluate the clinical applicability and prognostic value of this classification and to determine the incidence of malignant transformation. A retrospective clinical-pathological analysis was performed in a series of 4167 patients with 4574 biopsies, treated from 1979 to 1994. Simple (benign prickle cell) hyperplasia was the predominant grade in nodules, polyps, Reinke's oedema, granulomas, and papillomas, accounting for 37.6-68.6% of cases. In chronic laryngitis, abnormal (benign basal cell) hyperplasia was predominant with 43.9% of cases. Atypical ('risky') hyperplasia was observed almost exclusively in patients with chronic laryngitis (16.1%) and papillomas (10.1%), and only exceptionally in patients with vocal cord nodules (0.9%) and Reinke's oedema (0.3%). The percentage of malignant transformation in atypical hyperplasia was 11.6% (13/112 patients in 2-12 years), while in simple and abnormal hyperplasia, it was 0.3% (8/2920 patients in 1.5-11 years). The data support the concept of the Ljubljana classification dividing epithelial hyperplastic laryngeal lesions into benign (simple and abnormal hyperplasia), potentially malignant (atypical hyperplasia) lesions and carcinoma in situ.     

Current classification of precursor lesions of oral squamous cell carcinoma principles of the WHO classification 2005]

The WHO classification of oral tumours summarizes the precancerous squamous cell lesions under the term epithelial precursor lesions. For the first time three classification schemas that histologically categorize oral epithelial precursor lesions are used analogously. According to the WHO suggestion of 2005 the traditional schema of grading dysplasia as mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ continues to be used. In addition the concept of intraepithelial neoplasia is introduced as squamous intraepithelial neoplasia I-III. Squamous intraepithelial neoplasia III (SIN III) combines severe dysplasia and carcinoma in situ. The Ljubljana classification of squamous intraepithelial lesions was originally established to grade laryngeal epithelial precancerous lesions. The clear and succinct nomenclature and the simple clinical utility of the Ljubljana classification have also proven to be useful for oral epithelial precursor lesions: squamous cell (simple) hyperplasia; basal/parabasal cell hyperplasia (analogous to mild dysplasia and to SIN I); atypical hyperplasia (analogous to moderate-severe dysplasia and to SIN I-III and is also called risky epithelium); carcinoma in situ (analogous to WHO carcinoma in situ and to SIN III). Atypical hyperplasia (risky epithelium) and carcinoma in situ are defined as lesions requiring either total excision or close clinical monitoring.     

The Lublańska classification of precancerous lesions of the larynx

Laryngeal carcinomas are preceded by precancerous lesions in about 20% of cases. The macroscopical appearance of these lesions is not enough characteristic to define their malignant potential. The accurate identification of epithelial abnormalities of the laryngeal mucosa requires biopsy and microscopic evaluation. There are many histological classifications of laryngeal precancerous lesions used at present. Many of them are highly subjective and have low reproducibility. Moreover, the different grades of these classifications not always give distinct guidelines for clinician concerning the treatment modality. The Ljubljana classification seems to be easier, more readily applied and more reproducible. It uses the name "epithelial hyperplastic laryngeal lesion" (EHLL) which includes all alterations in laryngeal squamous epithelium. The four grades of EHLL are: 1. simple hyperplasia (thickening of epithelium due to augmentation of normal prickle cells), 2. abnormal hyperplasia (with increase of basal-like cells), 3. atypical, or risky hyperplasia (epithelium thickened by increase of basal-like cells with pronounced atypical features), and 4. carcinoma in situ (i.e. full thickness change with the features of malignancy but without stromal invasion). The criteria of Ljubljana classification are precise and gives a possibility to make a more clear-cut separation of cases with risk of developing carcinoma from those without it.     

成人喉乳头状瘤Pin1和CyclinD1的表达及意义

目的：探讨成人喉乳头状瘤中Pin1和Cyclin D1的表达情况、二者之间的相关性及在喉乳头状瘤恶变中的作用。方法：用免疫组织化学方法检测10例喉正常上皮组织、39例喉乳头状瘤、27例喉乳头状瘤伴中重度不典型增生及16例喉乳头状瘤伴癌变共计92例石蜡切片中Pin1和Cyclin D1的表达情况。结果：从正常喉上皮组织到喉乳头状瘤恶变组织的变化过程中,Pin1和Cyclin D1的表达逐渐增高（P〈0.05）;Cyclin D1在喉乳头状瘤组与伴不典型增生组之间表达差异无统计学意义（P〉0.0125）,其余各组间差异均有统计学意义（均P〈0.0125）;Pin1和Cyclin D1的表达具有显著正相关性（P〈0.05）。结论：Pin1和Cyclin D1在喉乳头状瘤恶变过程中发挥重要作用;Pin1过表达上调Cyclin D1过表达,可能是喉乳头状瘤恶变机制之一。     

Advantages and limitations of the autofluorescent diagnostics of the laryngeal cancer and precancerosis

Any endoscopic diagnostic procedure that is capable of giving exact information on laryngeal lesions without damaging the tissue has essential advantages over standard biopsy. Tissue autofluorescence is defined as a natural ability of tissue to fluoresce when exposed to a certain light wavelength. This feature is a consequence of the presence of fluorophores in the tissues, which are activated by a narrow wavelength range. However, due to their biochemical and biophysical characteristics, laryngeal precancerosis and cancer do not fluoresce when exposed to blue light. In the present study, we used Pentax’s System of Autofluorescent Endoscopy (SAFE 1000) to detect autofluorescence disturbances from laryngeal mucosa. Diagnostic parameters (sensitivity and specificity) of the microlaryngoscopy (MLS) and SAFE 1000 in the diagnosis of laryngeal precancerosis and carcinoma were compared and discussed. We have found that SAFE had a better sensitivity with regard to mentioned laryngeal pathology, but MLS had better specificity than SAFE. The overall diagnostic sensitivity in the diagnostics of laryngeal atypical hyperplasia and cancer with SAFE was 89%, as opposed to 73% with MLS. Diagnostic specificity of SAFE for all cases of laryngeal carcinomas and atypical hyperplasia was 78%. The specificity of MLS in diagnostics of laryngeal carcinomas cases was 98%, while that for cases of atypical hyperplasia was 100%. Many other conditions that have impact on autofluorescent features of laryngeal mucosa were also discussed.     

凋亡抑制蛋白Livin在喉癌中的表达和意义

目的研究凋亡抑制蛋白Livin在喉癌周黏膜、喉不典型增生和喉鳞状细胞癌(简称喉癌)组织中的表达以及与喉癌各临床因素的相关性。方法采用免疫组织化学SP法检测10例喉癌周黏膜,12例喉不典型增生和61例喉癌中Livin蛋白的表达,分析其与喉癌发生、发展及预后的关系。结果Livin在喉癌中阳性表达率为67.21%(41/61);在喉不典型增生中为25% (3/12);在喉癌周黏膜中表达阴性。在喉癌组中Livin高表达与临床分期、T分期、病理分化程度呈显著相关(P<0.05);与年龄、部位、淋巴转移无显著相关(P>0.05),随访发现该蛋白的表达与患者5年生存率无显著相关(P>0.05)。结论凋亡抑制蛋白Livin在喉癌的发生、发展中起着重要作用,尚不能作为判断患者预后的一项指标,该基因有望成为喉癌基因治疗的一个新的有效的靶点。     

喉鳞状细胞癌中Snail mRNA表达及临床意义

目的 探讨Snail mRNA在人喉鳞状细胞癌(简称喉癌)组织中的表达及与临床病理特征的关系,并探讨它在喉癌发生、发展中的作用及其临床应用价值.方法 应用原位分子杂交方法检测Snail mRNA在60例喉癌、30例喉不典型增生和20例喉慢性炎症组织中的表达.结果 60例喉癌组织中Snail mRNA的阳性表达率为70%...