宫颈上皮癌变过程中细胞DNA含量及形态的定量分析

应用ＭＰＶⅢ型显微分光光度计的检测及图像分析技术，对宫颈轻，中，重度非典型性增生细胞及正常细胞和癌细胞进行ＤＮＡ含量及形态的定量分析，结果表明：轻，中，重三个增生级别组的ＤＮＡ含量及细胞核面积与细胞异型程度成正比，且均高于正常组，低于宫颈癌组。我们认为，对宫颈非典型性增生细胞的ＤＮＡ含量及面积的测定，为宫颈非典型性增生的早期诊断，以及指导治疗方案的选择，开辟了一个新途径。     

化学诱癌过程中大鼠鼻咽上皮非典型增生与癌变的相关性分析

ＳＤ纯种大鼠８０只，皮下注射二亚硝基哌溱作鼻咽诱癌实验，３０只大鼠作对照，分批处死动物。结果大鼠鼻咽各种非典型增生４２例，各阶段癌３２例，其出现频率都随动物存活期延长而增加。癌变与鳞状上皮，柱状上皮和底层非典型增生呈正相关。几科所有发癌动物都同时伴随非典型增生。二者共存的比例很高，且有统计学意义。能看到癌变部位直接与非典型增生相的２３例中，癌旁病变全部是鳞状上皮非典型增生，其中１９例是基底层细胞非     

鼻咽原发性腺癌23例临床病理分析

目的:探讨鼻咽原发性腺癌的发病情况、临床规律及临床诊治、预后情况.方法:回顾性分析1995-05-2008-10在我院经过病理确诊和治疗的23例鼻咽腺癌的临床资料.普通型腺癌12例,涎腺型腺癌11例.17例单纯放疗,1例单纯手术治疗,3例术后辅助放疗,1例术后残留补救放疗,1例术前放疗.随访4～204个月(中位随访时间55个月),随访率100%,生存期计算自病理确诊日开始至死亡或随访截止日.利用SPSS 16.0软件包进行统计学分析,局控率、生存率分析采用Kaplan-Meier 法计算,颈淋巴结转移相关因素分析采用四格表的确切概率法.结果:本组病例占我院同期鼻咽癌病例总数的0.37%.发病年龄32～62岁,男女比例2.3∶1.颈部淋巴结转移率35%.5和10年局控率分别为64.8%和15.2%;5和10年生存率分别为78.2%和29.3%,病理类型、分化程度与淋巴结转移密切相关,差异具有统计学意义.结论:鼻咽腺癌临床表现与鼻咽癌类似,淋巴结转移主要与病理类型、分化程度有关;涎腺型、低度恶性普通型腺癌淋巴结转移少见,而高度恶性普通型腺癌淋巴结转移率高.虽放疗为主治疗可以取得较好生存率,治疗上应进一步探讨根据具体病理类型采取以手术为主或放疗为主的综合治疗.     

乳腺导管上皮癌变过程中树突状细胞的表达情况

目的　探讨乳腺导管上皮癌变过程中树突状细胞(DC)的表达。方法　选取常规石蜡包埋乳腺组织标本14 7例,分为正常对照组、单纯性增生组、不典型增生组、导管内癌+早期浸润癌组、浸润癌组。应用免疫组化方法分别检测其S10 0 +DC、HLA DR +DC和CD1a +DC的阳性表达情况。结果　浸润癌组S10 0 +DC和CD1a +DC阳性表达率分别为77.61%、5 6.72 % ,均显著高于其他组(P均<0 .0 5 )。导管内癌+早期浸润癌组、浸润癌组HLA DR +DC阳性表达率分别为10 0 .0 0 %、97.0 1% ,均显著高于其他组(P均<0 .0 5 )。不同标记阳性DC联合表达率在导管内癌+早期浸润癌组、浸润癌组较高,分别为3 3 .3 3 %、5 5 .2 2 % ,且这2组中无不同标记阳性DC均阴性表达病例。结论　在乳腺导管上皮癌变过程中均有不同标记阳性DC存在,其阳性表达率随增生性病变进展逐渐增高,进展为浸润癌时则显著增高,DC的阳性表达情况可用于评估乳腺癌患者局部免疫状态。     

乳腺腺纤维瘤癌变11例临床病理分析

目的：探讨乳腺腺纤维瘤癌变的临床病理特点。方法：对1963—2001年经病理证实的乳腺腺纤维瘤癌变11例进行分析，重点分析诊断方法、病理特点、治疗方式及预后因素。结果：11例均为手术检出，其中8例为管内癌，1例小叶原位癌，2例浸润性导管癌。保守性手术8例，根治术或仿根治术3例，随访3个月-25年，均健在。结论：乳腺良性肿瘤均应手术切除并做病理检查，本病属乳腺癌的早期病变，保守性手术治疗效果良好。     

CYTOMORPHOMETRIC ANALYSIS DURING CANCERATION OF NASOPHARYNEAL EPITHELIUM

Cellular morphology was quantitatively analysed by using the point-counting technique In 76 specimens inciuding 18 normal nasopharyngeal epithelia, 16 simple hyperplasia and metaplasia, 18 dysplasia and 24 untreated nasopharyngeal carcinoma (NPC). Altogether 19 morphometric parameters of the cell were measured and calculated. THe results showed that with malignant transformation of nasopharyngeal epithelium, the great majority of the cellular morphometric parameters gradually increased in numerical values while no marked difference was shown between normal nasopharyngeal epithelium and simple hyperplasia or metaplasia in terms of cytomorphometric characteristics. Most of the parameters in dysplasla changed significantly as compared with those in other three groups. Cytomorphometric analysis seems to give strong support to the concept that dysplasla is among the transition stages of disease process between normal nasopharyngeal epithelium and NPC. 19 parameters were processed with multivarite analysis an     

Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity

In this study, we examined the expression of cyclins, cyclin dependent kinase (CDKs) and CDK inhibitors by immunohistochemical analysis in 20 normal mucosa, 42 epithelial dysplasia (ED), and 117 oral squamous cell carcinoma. Neither Cyclin D1 nor CDK2 were detectable in normal tissue and ED. Their presence, however, was detectable in squamous cell carcinoma (SCCs) (Cyclin D1, 35.9%; CDK2, 66.7%). Cyclin E was detectable in 57.1% of severe ED and 62.8% of SCCs. For the CDK inhibitors, these proteins were detectable in all normal mucosa and most of the mild and moderate ED. For severe ED, expression of these proteins was not observed in some cases (p12(DOC-1), 14.3%; p16(INK4A), 28.6%; p27(KIP1), 7.1%). For SCCs, the expression of p12(DOC-1) was lost in 71.8%, p16(INK4A) in 69.2% and p27(KIP1) in 35.9%. These results suggest that elevated expression of cyclin D1, cyclin E, CDK2 and loss of p12(DOC-1), p16(INK4A) and p27(KIP1) may contribute to the multistep nature of oral carcinogenesis.     

Expression of p53 in premalignant and malignant squamous epithelium.

Using three antibodies (JG8, CM-1 and 1081) directed to the p53 protein, strong positivity was found in 16/47 (34.0%) of mucosal squamous cell carcinomas of the head and neck and in two squamous carcinoma cell lines (LICR-LON- HN5 and HN6Rr). The presence of the mutant p53 was confirmed in the cell lines as substitutions in exon 7 (codon 238, TGT greater than AGT) and exon 5 (codon 152, CCG greater than CTG) respectively. Positive staining was seen only in the undifferentiated cells and progressively lost as the cells keratinized, both in the tumour specimens and in the cell lines. Similar results were seen in areas of dysplasia, well removed from the site of the primary tumour. Staining of epidermal lesions showed positivity in 2/12 (16.6%) cases of Bowen's disease, 0/12 (0.0%) cases of solar keratosis, 0/10 (0.0%) basal cell carcinomas and in 3/20 (15.0%) squamous cell carcinomas. These results are discussed in relation to the multifocal origin of squamous cell carcinomas, the role of p53 mutations in squamous cell carcinomas from different sites and the significance of the 'basal' distribution of p53 as a normal growth regulator. The possible significance of the distribution of p53 in squamous epithelium as it relates to papilloma virus infection is also considered.     

Lectin histochemistry of normal and neoplastic nasopharyngeal epithelium.

The cell surface carbohydrate profile of formalin-fixed paraffin-embedded tissue sections of normal and neoplastic epithelium was evaluated using 9 plant lectins. Three lectins, namely Con A, RCA and WGA, showed a similar pattern and staining intensity from normal epithelium to metaplastic squamous epithelium and nasopharyngeal intraepithelial neoplasia (NPIN). However, a decrease in staining reactivity was observed in undifferentiated nasopharyngeal carcinoma. Significant differences in intensity and distribution were seen in UEA and cryptic PNA residue (after neuraminidase pretreatment) from normal nasopharyngeal epithelium to NPIN. Infiltrative undifferentiated carcinomas showed a heterogenous lectin binding pattern and altered intensity of lectin binding in one case of DBA and three cases of PNA (no neuraminidase pretreatment), suggesting a variation in expression of carbohydrate by tumour cells. These results indicate that neoplasia in nasopharyngeal epithelium is associated with alterations in terminal sialic acid, -Fucose residues and -Gal-D-GalNac residues present in the outer parts of glycoconjugates. SBA, VVL and BSL failed to stain any types of epithelia. Desialylation of tissues by preincubation with neuraminidase did not expose DBA, SBA, VVL and BSL binding sites. These findings may be used as a baseline for evaluation of lectin binding in preinvasive and invasive lesions of the nasopharynx.     

Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus

Esophageal carcinoma includes squamous cell carcinoma and Barrett's adenocarcinoma. The latter usually develops from a premalignant lesion named Barrett's esophagus. MUC genes are known to be specifically expressed in the normal, premalignant and malignant epithelia of various tissues. The aim of this study was to establish the pattern of MUC gene expression in the esophageal mucosa under normal conditions, and under pathological conditions such as squamous cell carcinoma, Barrett's esophagus and adenocarcinoma. Samples of esophageal control mucosa, metaplastic and malignant tissues were obtained from 40 patients undergoing esophagectomy for squamous cell carcinoma (n = 17), or Barrett's esophagus with adenocarcinoma (n = 23). In situ hybridization and northern blot were used with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7 genes to assess their expression in these samples. Submucosal glands of control esophageal mucosa expressed MUC5B, whereas MUC1 and MUC4 were found in both control epithelium and squamous cell carcinoma. MUC4 expression correlated with squamous cell differentiation. Barrett's adenocarcinoma exhibited various patterns of MUC gene expression, the strongest being in the well-differentiated mucinous adenocarcinomas. Barrett's metaplasia was also associated with a specific MUC gene expression pattern, since the gastric apomucin mRNAs, MUC5AC and MUC6, were expressed in gastric metaplasia, and the intestinal apomucin mRNAs, MUC3, MUC4 and mostly MUC2, in intestinal metaplasia. Residual expression of gastric apomucin mRNAs was found in intestinal metaplasia. From these results, we conclude that MUC genes can be considered reliable phenotypic markers of the esophageal cell differentiation, thus providing new insight into the development of Barrett's esophagus.     

Vitamin D receptor expression in normal, premalignant, and malignant human lung tissue.

BACKGROUND: There is a strong interest in identifying chemopreventive agents that might help decrease the burden of lung cancer. The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol), has been shown to have antiproliferative effects in several tumor types, mediated by the vitamin D receptor (VDR). This is the first comprehensive survey of VDR expression in a series of human lung tissues, including normal and premalignant central airway biopsies and lung tumors. METHODS: Immunohistochemical expression of nuclear and cytoplasmic VDR was examined in 180 premalignant or malignant bronchial biopsies from bronchoscopy of 78 high-risk individuals at the Roswell Park Cancer Institute and also in 63 tumor samples from 35 lung cancer patients from the University of Chicago Hospitals. Associations between clinicopathologic data and VDR expression were examined. RESULTS: VDR expression was present in many samples. In biopsies, VDR was commonly detected throughout the full epithelial layer. Most histologically normal (60%, 53 of 88) and metaplastic (61%, 39 of 64) samples had moderate to high nuclear intensity; dysplastic samples mostly had low nuclear intensity (10 of 18, 55%). In tumor samples, 62% (38 of 61) were lacking cytoplasmic VDR, with nuclear expression present in 79%(49 of 62). Analysis of all samples revealed a positive linear trend between proportion of samples with greater nuclear than cytoplasmic intensity and increasing histologic grade (P < 0.01). CONCLUSIONS: VDR expression spanned the lung carcinogenesis spectrum. Nuclear expression was similar across various histologies, whereas cytoplasmic expression decreased with increasing histologic grade. These results indicate that there is potential for the use of calcitriol as a chemopreventive agent against the development of lung cancer.     

Immunohistochemical localization of epidermal growth-factor and its receptor in normal, premalignant and malignant oral-mucosa

An important growth factor involved in epithelial carcinogenesis is the epidermal growth factor (EGF). The present study analyze the expression pattern of EGF and its receptor (EGFR) in different stages of tumour progression in oral mucosa (normal epithelium, non-dysplastic and dysplastic leukoplakias and carcinomas). Alterations in expression pattern of EGFR was not significant in the various tissues from normal mucosa to malignancy. In all these stages EGFR positivity was confined to the immature basal or basaloid cells. EGF however showed marked alterations in expression in different stages of tumour progression in oral mucosa. Most of the malignant cells were positive for EGF antibodies while, only a few lower layers of cells were stained in normal mucosa and in dysplastic leukoplakia lesions, more number of cells expressed EGF than normal tissue. The present study thus shows the autocrine role of the EGF and EGFR and the possibility of using EGF as a marker for tumour progression in oral mucosa.     

Differential responses of normal, premalignant, and malignant human bronchial epithelial cells to receptor-selective retinoids.

Using an in vitro lung carcinogenesis model consisting of normal, premalignant, and malignant human bronchial epithelial (HBE) cells, we analyzed the growth inhibitory effects of 26 novel synthetic retinoic acid receptor (RAR)- and retinoid X receptor (RXR)-selective retinoids. RAR-selective retinoids such as CD271, CD437, CD2325, and SR11364 showed potent activity in inhibiting the growth of either normal or premalignant and malignant HBE cells (IC50s mostly <1 microM) and were much more potent than RXR-selective retinoids. Nonetheless, the combination of RAR- and RXR-selective retinoids exhibited additive effects in HBE cells. As the HBE cells became progressively more malignant, they exhibited decreased or lost sensitivity to many retinoids. The activity of the RAR-selective retinoids, with the exception of the most potent retinoid, CD437, could be suppressed by an RAR panantagonist. These results suggest that: (a) RAR/RXR heterodimers play an important role in mediating the growth inhibitory effects of most retinoids in HBE cells; (b) CD437 may act through an RAR-independent pathway; (c) some of the RAR-selective retinoids may have the potential to be used in the clinic as chemopreventive and chemotherapeutic agents for lung cancer; and (d) early stages of lung carcinogenesis may be responsive targets for chemoprevention by retinoids, as opposed to later stages.