鼻咽癌旁柱状上皮鳞状化生过程中上皮性标志表达的变化

采用免疫组化方法,应用一组抗癌胚抗原（ＣＥＡ）、上皮膜抗原（ＥＭＡ）和不同分子量细胞角蛋白（ＣＫ）的抗体,对７８例鼻咽癌癌旁上皮的上皮性标志的表达进行了研究。结果表明,柱状上皮的储备细胞和鳞状上皮的基底细胞的上皮性标志的表达不同。在柱状上皮鳞状化生过程中,一方面是柱状上皮的储备细胞增生并转化为鳞状上皮的“基底细胞”,另二方面,这些“基底细胞”按正常鳞状上皮的分化程序,分化并发育为好状上皮,同时仍保留储备细胞的一些分化特征。因此,鳞状化生上皮与正常被覆鳞状上皮在上皮性标志的表达上仍存在一些差异。     

PCNA在宫颈鳞癌中的表达及其临床意义

目的 探讨ＰＣＮＡ基因过度表达在子宫上皮内瘤变及子宫颈鳞形细胞癌中的意义。方法 标本采用常规石蜡切片,ＨＥ染色及ＡＢＣ法免疫组化染色,光镜观察,并对增殖细胞核抗原指数进行计数。结果 从正常宫颈鳞状上皮到ＣＩＮⅡ级到子宫颈鳞癌,表达ＰＣＮＡ阳性的细胞范围和阳性强度呈明显增高的趋势,三者间ＰＣＮＡ ＬＩ差异有显著性。     

ANXA1，Ki-67抗原在宫颈上皮内瘤变和宫颈癌中的表达及其相互关系

目的：探讨膜联蛋白A1（Annexin A1,ANXA1）和细胞核相关抗原Ki-67在正常宫颈上皮、宫颈上皮内瘤变和宫颈鳞状细胞癌组织中的表达及其相关性。方法：应用免疫组化法检测56例宫颈上皮内瘤变（ CIN）,39例早期宫颈鳞状细胞癌（ SCC）和26例正常宫颈鳞状上皮组织中ANXA1和Ki-67的表达,分析两者之间表达的相关性。应用免疫印迹法检测正常宫颈组织、宫颈上皮内瘤变及宫颈鳞状细胞癌组织中ANXA1的蛋白表达情况。结果：在正常宫颈上皮中 ANXA1蛋白呈高阳性表达,随着宫颈病变的进展, ANXA1蛋白表达呈明显下降趋势。在正常宫颈上皮、宫颈上皮内瘤变和宫颈癌组织中ANXA1蛋白表达具有显著性差异（ P＜0.05）。在正常宫颈上皮和CIN组织中Ki-67抗原表达与ANXA1蛋白表达呈负相关（ P＜0.01）。结论：ANXA1蛋白在宫颈癌中低表达,并与抗原表达明显负相关,与宫颈癌发生、发展过程中凋亡抑制和增殖能力增强有关,可以作为预测宫颈鳞癌不良预后因素之一。     

Brenner瘤细胞分化的凝集素受体标记

研究７种生物素化的凝集素对卵巢Ｂｒｅｎｎｅｒ瘤不同分化方向和分化性质瘤细胞的标记特点，麦胚素、花生素受体在瘤细胞呈顶浆型表达是瘤细胞向腺上皮分化的标志；双花扁豆素受体瘤细胞膜阳性显示其向鳞状上皮分化倾向；ＷＧＡ、ＰＮＡ、兀鹰素（ＢＳ－１）和刀豆素在瘤细胞浆内弥漫性结合增强表明Ｂｒｅｎｎｅｒ瘤由良性、增生性向恶性转化。凝集素受体表达差异可做为Ｂｒｅｎｎｅｒ瘤细胞的分化标志，体现该瘤上皮成分分化，失分     

EB病毒基因在喉鳞状细胞癌中的表达

目的：ＥＢ病毒感染与喉鳞状细胞的发生发展是否有关迄今未明。本文目的在于了解ＥＢ病毒基因在喉鳞状细胞癌组织中的表达情况，探讨各种ＥＢ病毒基因产物在喉鳞状细胞癌发生发展中的生物学意义。方法：采用原位杂交和免疫组化技术，检测２９例不同分化类型喉鳞状细胞癌组织中ＥＢ病毒编码的小ＲＮＡ（ＥＢＥＲｓ）、潜伏感染膜蛋白（ＬＭＰ１）、ＥＢ病毒核抗原（ＥＢＮＡ－１）、溶解感染立即早期基因编码蛋白ＺＥＢＲＡ、早期基因编码蛋白ＥＡ－Ｄ、晚期基因编码蛋白ＶＣＡ和ＭＡ。结果：各检测指标在未分化癌、低分化和中分化鳞癌均有一定比例的阳性，但在２例高分化鳞癌均为阴性。发现ＥＢ病毒潜伏性和溶解性感染基因产物表达分别随着癌分化程度增高而减弱和增强。７例低分化和１例中分化鳞癌ＬＭＰ－１除胞膜和胞浆阳性外，胞核也呈明显阳性。２例低分化和１例中分化鳞癌中有少量癌细胞ＺＥＢＲＡ阳性。结论：部分喉鳞状细胞癌尤其是未分化和低分化鳞癌的发生发展与ＥＢ病毒感染密切相关，提示癌细胞的分化程度与ＥＢ病毒基因表达的差异有关。     

上皮膜抗原表达与胸腺瘤侵袭性的相关性分析

目的 采用免疫组织化学法对５１例胸腺瘤细胞中上皮膜抗原的表达进行了研究。方法 ＬＳＡＢ法，Ｍａｓａｏｋａ’ｓ临床分期，ＭＭ病理分类。结果 Ａ组：２３例，Ｂ组：２１例，Ｃ组：７例；ＥＭＡ表达阳性细胞大多为上皮样分化的瘤细胞。ＥＭＡ表达程度：①阴性１９例；②低度表达２２例；③中度表达５例；④高度表达５例。ＥＭＡ在侵袭性胸腺瘤和胸腺癌中表达较强。我们还观察到在有包膜浸润或包膜虽完整但细胞生长较活跃者，包     

上皮钙粘蛋白在口腔鳞状细胞癌组织中的表达与临床预后的相关性探讨

目的：探讨上皮钙粘蛋白的表达量与口腔鳞状细胞癌（SCC）的临床病理学参数及SCC患者的预后之间的关系。方法：采用免疫组织化学染色SABC法检测43例口腔鳞状细胞癌组织标本中的蛋白表达量并分析其与临床指标的关系。结果：上皮钙粘蛋白表达与口腔鳞状细胞癌的病理学分级（P=0．024），浸润类型（P=0．009）。淋巴结转移情况（P=0．023）及患者的生存年限（P=0．0146）有着密切的关系，蛋白表达越低，病理分级越高，浸润类型越复杂，出现淋巴结转移同时患者生存时间越短。但是，上皮钙粘蛋白表达与患者的年龄，性别及肿瘤的分化度之间无统计学意义。结论：上皮钙粘蛋白是口腔鳞状细胞癌患者一种极其重要的诊断标志物和可靠的预后因子。     

p-JNK JNK和PPAR γ在食管癌变过程中的

目的：探讨p-JNK JNK和PPAR γ蛋白在食管癌变过程中的表达及其意义。方法：采用免疫组织化学方法，研究食管正常鳞状上皮（15例）、食管鳞状上皮内瘤变（85例）和食管鳞状细胞癌（60例）组织中p-JNK JNK和PPAR γ蛋白的表达情况。结果：JNK在食管正常鳞状上皮、食管鳞状上皮内瘤变和食管鳞状细胞癌中的阳性表达率分别为20．0％、37．6％和55．0％，而p-JNK的阳性表达率分别为33．3％、55．3％和73.3％，JNK和p-JNK在食管鳞状细胞癌中的阳性表达率均明显高于食管正常鳞状上皮和食管鳞状上皮内瘤变（P〈0．05）。高级别食管鳞状上皮内瘤变中JNK、p-JNK的阳性表达率显著高于食管正常鳞状上皮和低级别食管鳞状上皮内瘤变（P〈0．05）。PPAR γ在食管正常鳞状上皮、食管鳞状上皮内瘤变和食管鳞状细胞癌中的阳性表达率分别为733％、45．9％和45．0％，食管鳞状上皮内瘤变和食管鳞状细胞癌中PPAR γ的阳性表达率明显低于食管正常鳞状上皮（P〈0．05）。食管鳞状细胞癌中JNK、p-JNK和PPAR3,的表达与肿瘤分化程度相关，JNK、p-JNK和PPAR3,的表达均随肿瘤病理分级的增高而降低（P〈0．05）。JNK、P—JNK和PPAR γ的表达与临床病理特征不相关（P〉0．05）。结论：在食管癌变过程中，JNK、p-JNK的表达呈增高趋势而PPAR γ的表达呈下降的趋势。但食管鳞状细胞癌中JNK／p—JNK和PPAR γ,的表达均随肿瘤分化程度降低而降低。提示JNK、p-JNK和PPAR γ在食管鳞状上皮癌变和进展过程中发挥不同作用，其机制比较复杂。     

Le^y抗原在卵巢上皮性肿瘤中的表达及意义

目的：探讨卵巢癌组织Le^y抗原的表达及其临床意义。方法：采用免疫组织化学SP法检测恶性、交界性、良性卵巢上皮肿瘤及正常卵巢组织中Le^y抗原的表达，并分析其与卵巢癌生物学特性之间的关系。结果：Le^y抗原在恶性卵巢上皮性癌中的阳性表达率为75．47％（40／53），明显高于交界性卵巢上皮性肿瘤（47．06％）及良性卵巢上皮性肿瘤（42．86％）（P均〈0．05）。正常卵巢组织中未检出Le^y抗原的表达。晚期卵巢上皮性癌的Le^y抗原的阳性表达率为84．21％，明显高于早期卵巢上皮性癌（53．33％），（P〈0.05）。结论：Le^y抗原与卵巢上皮性癌的发生、发展相关。Le^y抗原的表达可作为反映卵巢癌恶性潜能的一项新的指标。     

维生素甲及其合成类似物(retinoids)对化学致癌的预防作用

许多上皮组织在缺乏维生素甲时不能进行正常的细胞分化和生长,有些可能发生癌前病变——鳞状化生。如气管上皮的器官培养物,当缺乏维生素甲时失去正常的柱状纤毛上皮和粘液细胞,但加入维生素甲后就使角化的现象逆转,而鳞状细胞又变为柱状纤毛上皮和粘液细胞。前列腺器官培养物在化学致癌物引起的损害形成     

Identification of intestinal-type Barrett's metaplasia by using the intestine-specific protein villin and esophageal brush cytology

Villin is an actin-binding cytoskeletal protein required for brush-border formation in the normal small intestinal and renal proximal tubule epithelium. Villin is a marker of cell differentiation in small intestinal and renal cell lineages, and recent studies have shown villin to be highly expressed in 100% of intestinal-type Barrett's metaplasias. This epithelium is the single greatest risk factor for developing esophageal adenocarcinoma and arises when the normal esophageal squamous epithelium is replaced by a small intestine-like columnar epithelium after damage by chronic gastroesophageal reflux. In intestinal-type Barrett's metaplasia, the villin protein exhibits a highly characteristic staining pattern in which strong apical, brush-border staining of columnar epithelial cells is observed. In this study, the ability to identify intestinal metaplastic cells by using this distinct villin staining pattern was examined in endoscopic esophageal brushings from patients with confirmed Barrett's metaplasia. Esophageal brushings from 81% (17 of 21) of patients with Barrett's metaplasia demonstrated individual columnar cells with the characteristic villin staining pattern, whereas all normal esophageal squamous cells, blood cells, and gastric columnar cells were negative for villin expression. Northern blot analysis demonstrated villin mRNA expression in Barrett's metaplasia but not in the normal squamous esophagus or gastric mucosa from the same patients. The combined use of villin immunohistochemical analysis and esophageal brush cytology may provide a simple and effective method of detecting intestinal-type Barrett's metaplasia in patients at higher risk for developing this epithelium, such as those experiencing chronic gastroesophageal reflux symptoms.     

Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis

Regions where one type of epithelium replaces another (metaplasia) have a predilection for cancer formation. Environmental factors are closely linked to metaplastic carcinogenesis. In particular, cervical cancers associated with human papillomavirus (HPV) infection develop primarily at the transformation zone, a region where metaplastic squamous cells are detected in otherwise columnar epithelial-lined endocervical glands. Previously, we reported estrogen-induced multistage vaginal and cervical carcinogenesis in transgenic mice expressing HPV16 oncogenes in basal squamous epithelial cells. In the present study to investigate the threshold neoplastic response to exogenous estrogen, we treated groups of transgenic mice with lower hormone doses. A 5-fold reduction in estrogen dose induced squamous carcinogenesis solely at the cervical transformation zone compared with other reproductive tract sites. Further study delineated stages of transformation zone carcinogenesis, including formation of hyperplastic lower uterine glands and emergence of multiple foci of squamous metaplasia from individual stem-like glandular reserve cells, followed by neoplastic progression of metaplasia to dysplasia and squamous cancer. We propose that a combination of low-dose estrogen and low-level HPV oncogene expression biases transformation zone glandular reserve cells toward squamous rather than columnar epithelial fate decisions. Synergistic activation of proliferation by viral oncoprotein cell cycle dysregulation and estrogen receptor signaling, together with altered paracrine stromal-epithelial interactions, may conspire to support and promote neoplastic progression and cancer formation.     

Keratin subtypes in carcinomas of the uterine cervix: implications for histogenesis and differential diagnosis.

Normal epithelia and carcinomas of the human uterine cervix were studied by monoclonal antibodies chain specific for cytokeratins 4, 8, 10, 13, 14, 18, and 19. Most cells in 13 examined squamous carcinomas revealed a cytokeratin phenotype detected in ectocervical basal cells and endocervical subcolumnar reserve cells: 8+, 14+, 18+, 19+, 4-, 10-, 13-. We propose that these two cell types are closely related or identical and that squamous carcinoma of the cervix originates in this cell type. In more differentiated tumor cells cytokeratins 4, 10, and 13, which are present in suprabasal layers of the normal ectocervical epithelium, were coexpressed with basal cell cytokeratins. Thus, contrary to previous beliefs, all cytokeratins detected in carcinomas were also present in normal epithelium of uterine cervix. The cytokeratin profile of cervical adenocarcinomas corresponded to that of columnar endocervical cells (8+, 18+, 19+), although two of the three adenocarcinomas also expressed cytokeratin 4, which in the normal endocervix was detected in scattered single columnar cells only. The new monoclonal antibody DE-K14, specific for cytokeratin 14, proved a specific marker of subcolumnar reserve cells in the endocervix. It was also the only one that reacted with all cervical squamous carcinomas but with none of the cervical adenocarcinomas and, as such, has a potential value for pathological differential diagnosis of cervical tumors.     

Nasopharyngeal carcinoma and lymphoinfiltration

Originally referred to as 'lymphoepithelioma', undifferentiated and poorly differentiated nasopharyngeal carcinoma (NPC) tissues showed intense lymphoinfiltration. In a study of cryosections from 15 NPC tissues, we found that infiltrating lymphoid elements were comprised predominantly of lymphocytes, but plasma cells, follicular dendritic cells, and eosinophils were also commonly seen. Subpopulations of lymphocytes having the same phenotypes tend to aggregate, forming clusters or secondary follicles in stromatous tissues. The tumor areas were mainly infiltrated by T cells. Tumor cells and/or apparently normal epithelium in the paratumorous areas frequently expressed CD21, CD23, CD40 and a B lymphocytes carcinoma cross-reacting antigen (BLCa), all of which are involved in B cell activation and proliferation. CD21 and BLCa were strongly expressed near the surface of both squamous and columnar epithelium by those epithelial cells which are at advanced stage of differentiation, while CD40 was expressed by epithelial cells at earlier stages of differentiation located at or near the basement membrane. CD23 was mainly expressed by columnar cells and basal cells underlying squamous epithelium, but not, or weakly so, by flattened squamous cells or reserve cells underlying columnar epithelium. The large majority of tumor cells expressed CD40 and BLCa. A substantial proportion of them also expressed CD23, but the tumor cells were not reactive for CD21. Despite eosinophilic infiltration, IL-6 was not detected in tumor tissues. IL-1 was, however, detected in abundance in the cytoplasm of follicular dendritic-like cells and in the intercellular spaces in tumor areas and surrounding stromatous tissues. The immunobiology of NPC is discussed in the light of these observations.     

食管鳞癌细胞转铁蛋白受体的免疫组化研究

本文应用转铁蛋白受体（ＴＦＲ）的单克隆抗体ＯｋＴ９，以后蜡切片ＡＢＣ法研究了６７例食管鳞癌、６６例不典型增生及２９例正常食管鳞状上皮（对照组）ＴＦＲ的表达。结果表明，鳞癌组ＴＦＲ染色强度显著高于不典型增生组（Ｐ＜０．００５）和对照组（Ｐ＜０．０２５）；鳞癌组和不典型增生组ＴＦＲ染色阳性率显著高于对照组（Ｐ＜０．００５）；对照组ＴＦＲ阳性染色仅见于基底层或基底层和棘细胞层，不典型增生组ＴＦＲ阳性染色见于上皮全层或中下层，鳞癌组ＴＦＲ阳性染色见于上皮内已癌变的细胞和侵入肌层的癌细胞。三组中，间质ＴＦＲ染色均阴性。由此提出，ＴＦＲ在三组染色强度和阳性率的差异，可能为应用ＴＦＲ动态监测鳞状上皮细胞癌变提供了新的指标；可能用于食管鳞癌的普查与筛选以及作为生物导向诊断与治疗的一种潜在靶抗原。     

Keratin expression in normal uterine cervical epithelium and carcinomas of cervical origin

The immunohistochemical expression of keratins 7, 8, 10, 13, 14, 17, 18 and 19 was examined in formalin-fixed paraffin-embedded tissues of normal uterine cervical epithelium and carcinomas of cervical origin (4 squamous cell carcinoma in situ, 17 squamous cell carcinoma, 9 adenocarcinoma, and 1 adenoid basal carcinoma). A panel of 8 monoclonal antibodies capable of recognizing 8 individual keratin subtypes was employed using microwave oven heating and a labeled streptavidin biotin method. Ectocervical squamous epithelium expressed keratins 14 and 19 in the basal cell layer, and keratins 10 and 13 in the suprabasal cell layer. Endocervical columnar cells were found to express keratins 7, 8, 18 and 19, whereas the reserve cells expressed keratins 7, 8, 14, 17, 18 and 19. Most of the squamous cell carcinomas, both keratinizing and non-keratinizing, as well as the carcinoma in situ revealed a keratin phenotype detected in normal ectocervical squamous cells (keratins 10, 13, 14 and 19) and endocervical subcolumnar reserve cells (keratins 7, 17 and 18). The adenocarcinomas, both endocervical and endometrial type, were positive for keratins 7, 8, 17, 18 and 19. The adenoid basal carcinoma expressed all the keratins examined including the expression of reserve cell keratin. Reserve cell keratins were found mostly in squamous cell carcinomas, adenocarcinomas and adenoid basal carcinoma of cervical origin. Therefore, the keratin expression pattern indicates the origin of a variety of carcinomas of the uterine cervix from a common progenitor, endocervical reserve cells.     

Retinoid status and the control of keratin expression and adhesion during the histogenesis of squamous metaplasia of tracheal epithelium.

We induced vitamin A depletion to define early and late changes during the histogenesis of squamous metaplasia of hamster tracheal epithelium. An early change is the "minimal morphological change" (MMC), in which the mucociliary epithelium is separated from the basement membrane by a continuous layer of basal cells. Immunohistochemistry showed an exclusive localization of the keratins K5 and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining was observed above the basal layer with antibodies to K5, but upon progression of the lesion to a squamous focus all cells from basal to terminally differentiated were positive for K5 and K14. In contrast, when we used antibodies to the keratins K6 or K13 all cells were negative in the normal epithelium and in the MMC epithelium. Successive layers of suprabasal squamous cells found in squamous metaplasia failed to express normal epidermal differentiation marker keratins K1 and K10 but expressed the proliferation marker keratin K6 and the internal stratified epithelium keratin K13, not normally found in the epidermis or in the trachea. Hamster tracheal epithelial cells could be maintained in culture in serum-free medium for at least 4 weeks in the presence of retinoic acid (RA). In non-RA-containing medium, cells from vitamin A-deficient hamsters showed markedly reduced growth and an increase in the expression of keratins K5, K6, K13, and K14. Since our previous work had implicated retinoids in the control of cell adhesiveness, we were interested to find out whether changes in cell adhesion occur in vitamin A-deficient hamster tracheal epithelial cells, compared to normal cells. Functional assays demonstrated that hamster tracheal epithelial cells, obtained from non-RA-treated tracheas or maintained in culture, displayed reduced attachment to laminin, compared to RA-treated cells. Immunofluorescence studies did not show a decrease either in the alpha 6 integrin subunit, which was localized in the basal aspect of basal cells, or in basement membrane laminin. However, the expression of laminin-binding protein 37 decreased as the epithelium changed from pseudostratified to stratified. Therefore, a coordinated pattern of changes in keratin gene expression, as well as in the expression of laminin-binding protein 37, the precursor to the cell surface laminin receptor 67LR, and in adhesive properties takes place in tracheal epithelium when its phenotype changes from mucociliary to the preneoplastic stage of squamous metaplasia.     

Matrix metalloproteinases 21 and 26 are differentially expressed in esophageal squamous cell cancer.

Matrix metalloproteinase 21 (MMP-21) and MMP-26 (matrilysin-2) are the two newest members of the human MMP gene family that have both been suggested to play an important role in epithelial tumor progression and to be regulated via the Wnt signaling pathway. We studied their expression in 34 esophageal squamous cell carcinomas and non-neoplastic epithelium. MMP-21 protein was detected in cancer cells and inflammatory cells at the invasive front. Its expression was associated with invasion, inflammation, apoptotic and well-differentiated areas of the tumors, but not with cell proliferation. Unlike MMP-21, MMP-26 protein was already upregulated in incipient invasion and its expression associated with regions of low differentiation being more sporadic at the invasive front. MMP-21 was detected basally in KYSE-30 and OE21 esophageal squamous cell carcinoma cells, while MMP-26 was absent. None of the several cytokines and matrices tested were capable of consistently upregulating MMP-21 or MMP-26 mRNA expression in these two cell lines. Our results suggest that during esophageal tumorigenesis, MMP-21 and MMP-26 have different, unique expression patterns both being tightly regulated and induced in the vicinity of inflammation. MMP-21 may provide a marker for differentiating tumor areas. The putative role of MMP-26 as a marker of dysplasia and incipient invasion warrants further studies.     

Expression of vascular cell adhesion molecule-1 (CD 106) in normal and neoplastic human esophageal squamous epithelium

Vascular cell adhesion molecule-1 (VCAM-1), a key receptor for the leukocyte-associated integrin (VLA4), is a crucial mediator of leukocyte adhesion and has co-stimulatory functions in inflammation at various organ sites. Specifically, VCAM-1/VLA4 interactions have been shown to play important roles in the setting of cutaneous immune responses, such as psoriatic lesions in humans and acute Graft-versus-Host-Disease in mice. VCAM-1 is generally expressed on activated endothelial cells in inflamed tissues, mediating endothelium-leukocyte interactions, leading to leukocyte diapedesis to the site of inflammation. We report novel and unexpected membrane expression of VCAM-1 in the basal squamous epithelial strata of the normal human esophagus and distinct patterns of epithelial expression in esophageal pathology. To further delineate the differential expression patterns of VCAM-1 in the esophageal epithelium, we examined specimens from squamous cell carcinoma (SCC), adenocarcinoma, and Barrett's columnar cell metaplasia. VCAM-1 was strongly expressed in squamous cell carcinoma, but not adenocarcinoma nor columnar epithelia in Barrett's esophagus. VCAM-1 expression was focally accentuated at sites characteristic of microscopic tumor invasion in SCC, pointing to a potential role of VCAM-1 in the development of metastasis. In addition, in vitro immunofluorescence studies using OE21 cells, an esophageal squamous epithelial cell line, displayed distinct VCAM-1 immunoreactivity confined to mitotic and dividing cells. Cell cycle arrest caused a significant decrease in VCAM-1 immunoreactivity in OE21 cells. These data suggest a previously unappreciated role for VCAM-1 in esophageal squamous epithelial homeostasis and pathology.