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。     

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％，差异有非常显著意义（Ｐ＜０     

晚期喉癌边缘DNA含量和增殖细胞核抗原表达

目的探讨晚期喉癌边缘ＤＮＡ含量和增殖细胞核抗原（ＰＣＮＡ）表达与喉癌手术预后的关系。方法通过ＰＣＮＡ表达和ＤＮＡ含量检测，对３４例晚期喉癌边缘进行观察。结果肿瘤边缘１．０、０．５、０ｃｍ处粘膜，ＰＣＮＡ指数分别为８．６２％、１７．７６％和５０．３２％。ＤＮＡ指数分别为０．９８、１．０８２和１．４３６。统计学分析，１．０、０．５ｃｍ处粘膜与０ｃｍ处粘膜差异有显著性（Ｐ＜０．０１）。结论中、重度非典型增生的上皮在分裂，增殖等生物学行为方面已与轻度非典型增生和单纯性增生的上皮细胞不同，手术切缘应在中度非典型性增生的粘膜上皮以外，即０．５ｃｍ以外。     

c-myc癌基因蛋白在喉癌及癌旁不同距离组织中的表达研究

应用枸橼酸－ＬＳＡＢ－微波免疫组化法，检测ｃ－ｍｙｃ癌基因蛋白在喉癌、边缘区及癌旁０．５、１．０、１．５、２．０ｃｍ处粘膜和４例正常喉粘膜中的表达。结果：ｃ－ｍｙｃ蛋白在喉癌组织中的阳性表达率为９６．７％（２９／３０），与正常组织相比有极显著性差异（Ｐ〈０．０１）；在癌旁２．０ｃｍ处与１．５ｃｍ以内组织的表达存在着显著性差异（Ｐ〈０．０５）。ｃ－ｍｙｃ表达依正常粘膜→癌旁组织→癌呈逐步递增趋势。ｃ     

鼻咽癌活检组织及外周血白细胞EB病毒DNA的检测及其意义

目的：探讨鼻咽组织、外周血血白细胞ＥＢＶ基因组分布及与ＮＰＣ的关系。方法：采用ＰＣＲ法检测２６例ＮＰＣ,４例癌旁及１４例慢性鼻咽炎鼻 组织吸外周血白细胞中ＥＢＶ ＤＮＡ。同时采用酶免疫法测定血清ＶＣＡ－ＬｇＡ。结果：１．ＮＰＣ、癌旁及鼻咽炎组织ＥＢＶ ＤＮＡ无明显差异。２．ＮＰＣ与鼻咽炎组外周血白细胞ＥＢＶ ＤＮＡ有明显差异,Ｐ〈０．０５。３．ＮＰＣ与鼻咽炎组血清ＶＣＡ－ＩｇＡ之间存在明显差异。Ｐ     

成纤维细胞生长因子与鼻息肉上皮细胞增殖

为探讨成纤维细胞生长因子（ｆｉｂｒｏｂｌａｓｔｇｒｏｗｔｈｆａｃｔｏｒ,ＦＧＦ）在鼻息肉组织中的表达及其与鼻息肉上皮细胞增殖之间的关系,将２６例鼻息肉标本及１４例下鼻甲标本行ＦＧＦ和增殖细胞抗原（ｐｒｏ－ｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ,ＰＣＮＡ）的免疫组化染色,光镜观察,结果发现ＰＣＮＡ在鼻息肉组的阳性率（７８．６％）显著高于下鼻甲组（０．０％）,ＦＧＦ在鼻息肉组的上皮及腺体的阳性表达率明显高于下鼻甲组（Ｐ＜０．０１,Ｐ＜０．００１）,且二者的表达具有显著正相关（Ｐ＜０．０１）。我们推测ＦＧＦ对鼻息肉上皮及腺体细胞的增殖具有促进作用并参与鼻息肉的形成。     

喉鳞癌中增殖细胞核抗原和p53蛋白表达的临床意义及其相互关系

本文以ＬＳＡＢ免疫组化方法，用单克隆抗体ＰＣ１０和ＤＯ－１对３０例喉鳞癌及１０例对照组（声带息肉）的增殖细胞核抗原（ＰＣＮＡ）与ｐ５３蛋白表达进行研究，探讨其生物学意义。结果发现：１）喉鳞癌组织ＰＣＮＡ阳性表达率为１００％（ＰＣＮＡ－ＬＩｓ１６％～９２％），强阳性率为３６７％（１１／３０），对照组６例阴性，４例弱阳性表达（ＰＣＮＡ－ＬＩｓ＜１０％），试验组阳性表达率及表达程度明显高于对照组（Ｐ＜００５）。２）ｐ５３蛋白在喉鳞癌中阳性表达率为６６７％，对照组全部阴性，有显著差异（Ｐ＜００５）。３）在喉鳞癌组织中，ＰＣＮＡ和ｐ５３蛋白表达与临床分型、Ｔ分期及病理分化程度无显著关系（Ｐ＞００５），与淋巴转移及术后生存率关系密切（Ｐ＜００５）。４）ＰＣＮＡ与ｐ５３蛋白表达正相关。提示：１）喉鳞癌的增殖活性显著增强，ｐ５３基因突变与喉鳞癌的发生和发展有关。２）检测ＰＣＮＡ和ｐ５３蛋白有助于喉鳞癌的早期诊断和鉴别诊断，帮助治疗决策及判断预后。３）ｐ５３对ＰＣＮＡ有调节作用，为研究肿瘤的发生机理和寻找防治对策提供了新的理论依据。     

晚期喉癌边缘DNA含量和增殖细胞核抗原表达

目的 探讨晚期喉癌边缘ＤＮＡ含量和增殖细胞核抗原（ＰＣＮＡ）表达与喉癌手术预后的关系。方法 通过ＰＣＮＡ表达和ＤＮＡ含量检测，对３４例晚期喉癌边缘进行观察。结果 肿瘤边缘１．０、０．５、０ｃｍ处粘膜，ＰＣＮＡ指数分别为８．６２％，１７．７６％和５０．３２％。ＤＮＡ指数分别为０．９８、１．０８２和１．４３６。统计学分析１．０、０．５ｃｍ处粘膜０ｃｍ处粘膜差异有显著性（Ｐ〈０．０１）。结论 中、重度非     

垂直部分喉切除术后声功能的客观定量评价

为客观定量评价喉癌生趣部分喉切除术后患者的发音功能，采用喉声气流仪分别对行垂直半喉切除术后的喉癌患者３０例（按术后２年，３￣１０年分为Ａ、Ｂ两组），和正常男性（Ｃ组）３０例进行声功能测试。结果显示：Ａ、Ｂ组与Ｃ组比较平均气流率（ＭＦＲ）、声强、最长发音时间（ＭＰＴ）有极显著性差异（Ｐ〈０．０１）；发声频率之间有显著性差异（Ｐ〈０．０５）；Ａ组与Ｂ组比较其声强、ＭＦＲ、ＭＰＴ有极显著性差异（Ｐ〈０．     

喉癌表皮生长因子和c—erb B—2基因表达的免疫组化研究

对４４例喉鳞癌组织分别进行了表皮生长因子（ＥＧＦ）和ｃ－ｅｒｂＢ－２基因免疫组化研究。结果是：①ＥＧＦ主要位于细胞浆肉，ｃ－ｅｒｂＢ－２主要位于细胞膜；②ＥＧＦ染色阳性为２８例（６３．６％），ｃ－ｅｒｂＢ－２染色阳性２３例（５２．３％）；③ＥＧＦ阳性率随病理学分级递增而增高；④ｃ－ｅｒｂＢ－２阴性病例的术后复发或死亡率为７３．９％，而ｃ－ｅｒｂＢ－２阴性病例术后复发或死亡率４２．９％。提示，喉鳞癌     

Reduced expression of p27 is correlated with progression in precancerous lesions of the larynx

OBJECTIVES: Factors related to malignant transformation of laryngeal precancerous lesions remain largely unknown, so we investigated the relationship between the expression of p27 and precancerous laryngeal lesion. STUDY DESIGN: In this study we investigated the expressions of p27 and p53 protein in 56 cases with laryngeal precancerous or cancer lesions (20 cases of hyperplasia, 19 of dysplasia, and 17 of squamous cell carcinoma), and went on to evaluate the relationship between immunoreactivity of each of them and the histological findings. We also evaluated the correlation between immunoreactivity and proliferative activity with the aid of Ki-67 nuclear antigen staining. METHODS: A retrospective study was performed in 56 cases (20 with epithelial hyperplasia, 19 with epithelial dysplasia and 17 with laryngeal cancer). Immunohistochemistry was performed to investigate expression of p27, p53 protein and Ki-67 nuclear antigen staining, using the avidian-biotin-peroxidase complex technique. RESULTS: p27 immunostaining was observed in 12 out of 20 cases of hyperplasia (60%), six out of 19 cases of dysplasia (31%), and 2/17 (12%) of carcinoma. We found significant association between p27 immunostaining and the histological findings. On the other hand, p53 immunostaining was observed in 6/20 (30%) of hyperplasia, 3/19 (16%) of dysplasia, and 7/17 (41%) of carcinoma. No significant association was found between p53 and the histological findings. CONCLUSIONS: Our results revealed that immunohistochemical assessment of p27 in bioptic samples of laryngeal precancerous lesions might be useful in selective patients who should undergo a more specific follow-up evaluation.     

喉非典型增生和鳞癌的PCNA,p21表达及其意义

为探索增殖细胞核抗原和ｐ２１在喉非典型增生与其转化后的鳞癌中的表达有无差异。     

Treatment with CO2 laser of premalignant glottic epithelial lesions

Pre-malignant lesions of the larynx can degenerative into invasive carcinoma. There is not an universally accepted classification and treatment. We present our experience in the treatment with endoscopic CO2 laser for the pre-malignant glottic epithelial lesions. At the same time we carry out a review of the literature published. During a period of ten years we have treated 69 patients with one of these techniques: resection of the epithelial lesion or vaporization. The election of the technique depends on the size of the lesion, the macroscopic aspect, anterior commissures involvement and the surgeons experience. The histological findings were: 53.6% keratosis and 23.2% mid dysplasia both of them treated with vaporization and resection; 14.5% moderate dysplasia and 8.7% severe treated with resection of the lesion. There were no important complications during the operation. Recurrence occurred in 7 patients (10%) but after treatment all of them were free of disease during the follow-up period, they didn't progress to carcinomatosis. 9 patients (13%) had a malignant evolution: 3 keratosis, 1 mild dysplasia, 3 moderate dysplasia and 2 severe dysplasia. Only one case (1.5%) underwent total laryngectomy. The early diagnosis and an appropriate treatment reduced the possibilities of malignant transformation. The therapy with CO2 laser is the treatment of choice in this kind of lesions.     

Cell proliferation and p27Kip1 expression in endophytic schneiderian papillomas

OBJECTIVE: To clarify epithelial cell proliferation and p27Kip1 expression along the stepwise histological changes from endophytic schneiderian papillomas to associated carcinomas. STUDY DESIGN: Retrospective investigation involved surgical specimens from 58 patients. METHODS: Immunohistochemical assessment involved the nuclear Ki67 antigen expressed in proliferating cells. Further, the cyclin-dependent kinase (cdk) inhibitor p27Kip1 was assessed. Binding of p27Kip1 to the cyclin E-cdk2 complex inhibits this kinase, which results in cell cycle arrest. The expression rates of both proteins were compared between nonpapillomatous nasal mucosa, endophytic schneiderian papillomas, carcinoma in situ, and invasive squamous cell carcinomas. Statistics involved the Wilcoxon and Mann-Whitney u tests. Significance was set at P <.05. RESULTS: Comparable cell proliferation rates were observed between non-papillomatous nasal mucosa and cylindrical cell papillomas. Significant increases in cell proliferation were found along the stepwise series of histological changes involving non-papillomatous nasal mucosa, columnar epithelium in inverted papillomas, transitional and squamous metaplasia in inverted papillomas, and dysplastic inverted papillomas (P <.05, respectively). A tendency toward increased cell proliferation in carcinoma in situ compared with dysplastic inverted papillomas was present; however, this was not statistically significant. The expression rates of p27Kip1 were comparable between non-papillomatous nasal mucosa and all histological subtypes within nondysplastic endophytic schneiderian papillomas. Significantly reduced p27Kip1 expression was found in surface cells in dysplastic compared with non-dysplastic inverted papillomas, as well as in the total number of cells in carcinoma in situ compared with dysplastic inverted papillomas (P <.05, respectively). CONCLUSIONS: Inverted papillomas but not cylindrical cell papillomas show increased cell proliferation compared with nonpapillomatous nasal mucosa. Stepwise increases in cell proliferation accompany the consecutive histological changes within inverted papillomas. Among them, increased cell proliferation along with the development of dysplasia and carcinoma in situ is associated with reduced p27Kip1 expression.     

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.     

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.     

窄带成像内镜在喉癌诊断中的应用

目的 探讨窄带成像(narrow band imaging,NBI)内镜在喉癌及其癌前病变诊断中的应用价值.方法 自2008年12月至2009年7月对122例怀疑有喉癌或癌前病变的患者选用具有普通白光和NBI两种观察模式的电子内镜进行咽喉部的检查.对发现的病灶依次使用白光和NBI模式进行分类和病灶性质的判断,以病理诊断作为金标准,比较两种观察模式对喉癌的诊断作用.结果 122例患者中共发现了149个病灶,其中息肉16个,炎性反应7个,单纯性增生24个,轻度不典型增生17个,中度不典型增生6个,重度不典型增生6个,原位癌9个,浸润癌64个.NBI内镜对喉部病变的正确诊断率是90.6%(135/149),高于普通白光内镜的75.2%(112/149),两者比较差异有统计学意义(x~2=12.514,P<0.001).NBI内镜对喉癌诊断的敏感性为93.2%(68/73),高于普通白光内镜的68.5%(50/73,x~2=14.317,P<0.001).结论 NBI内镜通过识别黏膜表面微细血管形态变化提高对喉癌诊断的敏感性和喉部病变诊断的正确率,从而增强内镜在喉癌术前诊断和术后随访中的作用.     

Mucoepidermoid carcinoma of salivary glands: the prognostic value of tumoral markers

INTRODUCTION: Mucoepidermoid carcinoma is one of the most frequent malignant lesions of salivary glands. The treatment is based on clinical, paraclinical and histological data. Several studies on the prognostic value of molecular markers for these cancers were made with contradictory results. The aim of this retrospective study was to analyze the prognostic value of molecular markers of salivary gland mucoepidermoid carcinoma. MATERIAL AND METHODS: Sixteen patients were treated for mucoepidermoid carcinoma of principal and/or accessory salivary glands between 1994 and 2003. An immunohistochemical study of archive specimen was performed. Nine markers were specifically studied: 4 proteins/oncoproteins (p53, bcl2, c-erb-B2 and cd117), 2 markers of proliferation (PCNA and Ki67), 1 growing factor receptor (EGFR), 1 epithelial adhesion molecule (E-cadherin), and 1 angiogenic cytokine (PDGF). RESULTS: Nine men and 7 women were included, with a mean age of 43.7 years (14-80). The mean diameter of tumors was 3.1 mm (1-14), and the parotid gland was the most frequent location. The mean global survival rate was 57.3 months with a median of 55 months. The 2 to 5 years survival expectation rate were 82.5% and 46.4% respectively. The mean survival rate for women was superior to that of men (P=0.043). The expression of p53 and the high expression rate of EFGR were bad prognostic factors (respectively P=0.049 and P=0.012). The expression of PCNA was linked to the location (mainly the salivary gland) and to the diameter of the tumor (respectively P=0.037 and P=0.029). The degree of EFGR positivity and the histological grade were linked (P=0.027). DISCUSSION: The strong expression of EGFR was statistically linked to the histological tumor grade. The degree of PCNA positivity seemed to be associated to the preferential location in the main salivary glands and to the diameter of the tumor. The strong expression of p53 and EGFR were bad prognostic factors. These retrospective results need to be confirmed by prospective randomized and larger studies. EGFR and p53 were significant negative prognostic factors. EGFR was highly correlated to the histological grade, making it an interesting target for further investigation.     

Significance of p53 expression in non-tumoral epithelium adjacent to oral squamous cell carcinomas

Alterations of the p53 gene are the most frequently documented genetic abnormalities in human cancer. The aim of the present study was to analyse if this alteration is an early event in oral tumorigenesis and if the suprabasal expression of p53 is a marker of the presence and severity of epithelial dysplasia. Immunohistochemical p53 expression in 78 specimens of oral squamous cell carcinoma and non-tumoral adjacent epithelium was analysed. Non-tumoral epithelium was observed in 53 cases (67.9 per cent), being normal in six cases (7.6 per cent), hyperplastic in 24 cases (30.7 per cent) and dysplastic in 48 cases (61.5 per cent). Epithelial dysplasia was mild (23 cases, 47.9 per cent); moderate (23 cases, 47.9 per cent) and severe (two cases, 4.1 per cent). Twenty-one cases of the dysplasias (43.8 per cent) expressed p53. No p53 expression appeared in any normal epithelium. Basal p53 expression always appeared in mild dysplasias (two cases). Suprabasal p53 expression appeared in mild and moderate dysplasias in nine cases and in one severe dysplasia. No statistical correlation was observed between suprabasal expression of p53 and the presence or severity of the dysplasia. The expression of p53 is an early event in oral tumorigenesis but it does not behave as an objective marker of the presence or severity of epithelial dysplasia.