宫颈上皮内瘤变及宫颈鳞癌组织中survivin、COX-2的表达变化及意义

目的探讨survivin和COX-2在宫颈上皮内瘤变（CIN）及宫颈鳞癌中的表达变化。方法采用免疫组化法检测52例宫颈鳞癌、30例CIN和15例正常宫颈组织中的survivin和COX-2。结果survivin在正常宫颈组织中表达均阴性,CIN中阳性表达率为43．33％、宫颈鳞癌为67．31％;COX-2在正常宫颈组织中的阳性表达率为6．67％、CIN为40．00％、宫颈鳞癌为65．38％;不同宫颈组织的smvivin、COX-2阳性表达率相比,P均〈0．05。Sur-vivin表达与宫颈鳞癌的临床分期、淋巴结转移、肌层浸润深度及组织分级有关,P均〈0．05;COX-2的表达与宫颈癌淋巴结转移、肌层浸润深度及组织分级有关,P均〈0．05。结论CIN及宫颈鳞癌组织中survivin、COX-2表达增强,其表达与宫颈鳞癌的分化程度及淋巴转移、肌层浸润深度有关。     

宫颈鳞癌组织中cFLIP mRNA、Caspase-8 mRNA的表达变化及意义

目的寻找有效预测宫颈癌转移和评估预后的生物学指标。方法采用原位杂交法检测46例宫颈鳞癌组织、21例上皮内瘤样病变（CIN）及26例正常宫颈黏膜组织中Fas相关死亡区域蛋白样IL-1β转换酶抑制蛋白（chap）mRNA及Caspaae-8mRNA。结果cFLIP mRNA在宫颈鳞癌、CIN及正常黏膜组织中阳性表达率依次为76．1％、28．6％、15．4％，两两比较，P均〈0．05；cFLIP mRNA表达与宫颈鳞癌分化程度及淋巴结转移有关（P均〈0．05）。宫颈鳞癌、CIN及正常黏膜组织中Caspase-8mRNA阳性表达率分别为9．1％、9．5％、57．1％，两两比较，P均〈0．05；Caspase-8 mBNA表达与宫颈鳞癌分化程度有关（P〈0．05）。cFLIP mRNA、Caspase-8mRNA表达呈负相关（r=-0．642，P〈0．05）。结论在宫颈癌发展中cFLIP及Caspase-8分别发挥正负调节作用，Caspase-8可能通过抑制cFLIP的表达限制肿瘤细胞的侵犯和转移。二者联合检测有助于评估患者病情，为临床治疗方案的制定提供参考。     

宫颈鳞癌组织中VEGF-C、VEGFR-3的表达变化及意义

目的观察血管内皮生长因子C（VEGF-C）及其受体（VEGFR-3））在宫颈上皮内瘤变（CIN）及宫颈鳞癌组织中的表达变化,探讨其与宫颈癌发生发展及浸润转移的关系。方法采用免疫组化SP法检测11例正常宫颈组织、19例CIN及47例宫颈鳞癌组织中的VEGF-C、VEGFR-3。结果VEGF-C与VEGFR-3在正常宫颈组织、CIN及宫颈鳞癌组织中的表达依次增高,三者相比,P〈0．05。在宫颈鳞癌组织中VEGF-C与VEGFR-3的表达有关（P〈0．01）,淋巴结转移组VEGF-C与VEGFR-3的阳性表达率明显高于无转移组（P〈0．05）。结论VEGF-C和VEGFR-3在宫颈鳞癌发生发展及淋巴转移过程中发挥重要作用。     

P53、PTEN在宫颈上皮内瘤样病变中的检测及意义

目的检测基因表达产物P53和PTEN蛋白在正常宫颈上皮、各级宫颈上皮内瘤样病变（CIN）以及宫颈鳞状细胞癌（SCC）组织中的表达水平,探讨其与CIN病理学及分级的关系。方法采用SP免疫组化法检测10例正常宫颈上皮、55例CIN及15例SCC组织中P53、PTEN蛋白的表达情况。结果P53蛋白阳性表达率在正常宫颈鳞状上皮、CIN和SCC中分别为0、41．82％、73．33％,两两比较有统计学差异（P均〈0．05）。在各CIN分级中,P53蛋白阳性表达率比较无统计学差异（P〉0．05）;PTEN蛋白在正常宫颈鳞状上皮、CINI级、CINII级、CINⅢ级及SCC中阳性表达率比较均无统计学差异（P均〉0．05）。结论P53参与了CIN、SCC的发生,PTEN在CIN、SCC中可能起到有限的作用。     

食管鳞癌中HIF-1α、Bax、Bcl-2的表达及意义

采用RT-PCR及免疫组化技术检测食管鳞癌和其正常食管上皮中低氧诱导因子（HIF-1α）的表达,用免疫组化SP法检测Bax和Bcl-2蛋白在食管鳞癌及其正常上皮中的表达。结果：食管鳞癌中HIF-1α基因和蛋白阳性表达率分别为96．0％和94．0％,正常食管上皮中未见表达,其阳性表达与食管鳞癌的组织学分级、pTNM分期及淋巴结转移呈正相关（P均〈0．05）。Bax和Bcl-2蛋白阳性表达率分别为80．0％和76．0％,正常食管上皮中未见表达。Bax蛋白表达水平与食管鳞癌淋巴结转移呈正相关（P〈0．05）,Bcl-2蛋白在不同组织学分级间表达差异显著（P〈0．01）。HIF-1α蛋白与Bax、Bcl-2蛋白之间表达呈正相关（P〈0．05）。认为HIF-1α是食管鳞癌发生发展的一个关键基因,HIF-1α、Bax、Bcl-2在食管鳞癌发生发展过程中有协同作用,联合检测这三者在食管鳞癌中的表达有助于其早期诊断、治疗和预后判断。     

热休克蛋白与宫颈癌放射敏感性的相关性

目的探讨热休克蛋白（HSP）在不同放射敏感性宫颈癌组织中的表达。方法将152例宫颈癌放疗前病理标本依据放疗效果分为敏感组46例、不敏感组106例,采用免疫组化法检测各组标本中的HSP27、HSP70和HSP90的表达。结果宫颈癌组织中HSP27、HSP70和HStD0表达明显高于癌旁组织（P均〈0．01）;肿瘤组织病理分级与HSP70表达强度呈正相关（P〈0．05）。不敏感组HSP27、HSP90表达明显高于敏感组（P〈0．01）。结论检测HSP27、HSP70和HSP90表达水平可以作为宫颈癌细胞的放射敏感性及预测疗效的指标。     

p53和Bcl-2蛋白在舌鳞癌组织中的表达及意义

目的 研究p53和Bcl-2蛋白在舌鳞癌和癌前病变中的表达及意义。方法 采用免疫组化SP法检测38例舌鳞癌（A组）、20例13腔癌前病变（B组）及10例正常口腔舌上皮组织（C组）中p53和Bcl-2蛋白的表达情况。结果比较A、B、C三组,p53和Bcl-2蛋白的表达在A组与C组、B组与C组之间,P均〈0．05,在A组与B组之间,P〉0．05;ps3蛋白异常表达在淋巴结转移组显著高于无转移组,P〈0．05;Bcl-2蛋白高表达与p53蛋白高表达之间无相关性,P〉0．05。结论p53和Bcl-2蛋白高表达与舌鳞癌的发生、发展密切相关。     

宫颈癌组织中Fhit、survivin和Bcl-2的表达变化及意义

目的观察脆性组氨酸三联体（Fhit）、生存素（survivin）和Bcl-2在宫颈癌组织中的表达变化,并探讨其意义。方法采用免疫组化SP法检测30例正常宫颈组织、80例宫颈上皮内瘤变（CIN）组织、63例宫颈癌组织中的Fhit、survivin和Bcl-2。结果正常宫颈组织、CIN及宫颈癌组织中的Fhit失表达率分别为0、31.25%和63.49%;survivin的表达阳性率分别为0、46.25%和77.77%;Bcl-2的表达阳性率分别为6.67%、47.50%和82.54%（P均〈0.05）。Fhit表达缺失与病理学分级、临床分期和淋巴结转移无关（P均〉0.05）;survivin、Bcl-2阳性表达与宫颈癌病理学分级、临床分期和淋巴结转移有关（P均〈0.05）。结论宫颈癌组织中Fhit呈失表达、survivin、Bcl-2呈高表达,三者参与了宫颈癌发病,且survivin、Bcl-2与宫颈癌病理学分级、临床分期和淋巴结转移有关。     

MDM2和PTEN在宫颈鳞癌中的表达意义

采用免疫组化法检测50例宫颈鳞癌组织、30例癌旁不典型增生组织及50例正常宫颈组织中的PTEN和MDM2表达。结果MDM2蛋白在正常宫颈组织、癌旁非典型增生组织、鳞癌组织中的表达率分别为0、33．3％、64．0％;PTEN蛋白表达率分别为100％、70％、40％;PTEN、MDM2阳性表达与宫颈癌的发生发展均呈负相关（P〈0．05）。提示PTEN和MDM2可能在宫颈癌的发生发展中起重要作用。     

食管鳞癌组织中E—cadherin、VEGF的表达变化及意义

目的观察食管鳞癌组织中上皮性钙黏附蛋白（E—cadherin）和血管内皮生长因子（VEGF）的表达变化,并探讨其临床意义。方法采用免疫组化sP法检测60例食管鳞癌组织和癌旁正常组织中的E-cadherin、VEGF。结果食管鳞癌组织中E—cadherin表达阳性34例（56．6％）、VEGF表达阳性42例（70．0％）,癌旁正常组织中分别为55例（91．6％）、24例（40．0％）,两组比较,P均〈0．05。E-cadherin、VEGF表达与食管鳞癌临床分期、肿瘤浸润深度及淋巴结转移有关（P均〈0．05）。结论食管鳞癌组织中E—cadherin表达降低,VEGF表达升高;二者与食管鳞癌的浸润、转移有密切关系。     

肝细胞癌热休克蛋白70过表达与自发性癌细胞凋亡

目的探讨肝细胞癌（hepatocellularcarcinoma,HCC)热休克蛋白70（heatshockproteins70,HSP70）的表达及其与自发性癌细胞凋亡的关系。方法采用免疫组化SP法和原位末端转移酶标记法（TUNEL）检测68例HCC手术标本中HSP70表达和细胞凋亡指数,以癌旁肝组织作为对照。结果HCC和癌旁组织中HSP70阳性率分别为71%和28%,过表达分别为53%和21%,两组之间差异有非常显著意义（P＜0.01),HSP70阳性率和凋亡指数有正相关关系（r＝0.8765,P＜0.05),两者都随HCC组织学分级增高而增加。结论HCC组织中存在HSP70过表达和自发性癌细胞凋亡,两者正相关性机理尚不明了,可能是HCC生物学恶性行为的标志。     

宫颈病变组织中Vimentin、P16INK4A、Smad4的定位、表达及其在EMT中的作用

目的 观察Vimentin、P16INK4A和Smad4在宫颈癌及前期病变中的定位与表达水平,探讨其对宫颈癌细胞上皮—间质转化（EMT）的影响和可能机制.方法 免疫组织化学染色方法检测30例慢性子宫颈炎、30例低级别宫颈上皮内瘤变（CIN）、30例高级别CIN和30例宫颈癌中Vimentin、P16INK4A和Smad4的表达水平和定位.结果 Vimentin、P16INK4A和Smad4在各宫颈病变组织中呈不同程度阳性表达,在细胞质和细胞核均可表达.宫颈癌组织Vimentin 表达水平较慢性子宫颈炎、低级别CIN、高级别CIN高（P均＜0.01）.慢性子宫颈炎组织中P16INK4A阴性表达,在CIN和宫颈癌组织中表达水平升高（P均＜0.01）.慢性子宫颈炎组织中Smad4在细胞核与细胞质均高表达,低级别CIN、高级别CIN和宫颈癌组织中Smad4细胞核表达水平降低（P均＜0.01）.Spearman相关分析显示,120例宫颈病变组织中Smad4核表达与P16ININKA核质表达均呈负相关（r分别为-0.274、-0.387,P均＜0.01）,Smad4核表达与Vimentin核表达亦呈负相关（r=-0.209,P＜0.05）,P16INK4A核质表达与Vimentin核表达均呈正相关（r分别为0.334、0.443,P均＜0.01）.宫颈癌中Vimentin、P16INK4A和Smad4无论细胞核表达或细胞质表达均与宫颈癌的分化和年龄无相关关系（P均＞0.05）.结论 Vimentin、P16INK4A和Smad4在各宫颈病变组织细胞质和细胞核中呈不同程度阳性表达.Vimentin核表达是反映宫颈癌细胞EMT的良好指标,P16INK4A核表达和Smad4核表达与宫颈癌细胞EMT密切相关.     

Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma

AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageai carcinoma and adjacent normal tissues. METHODS: The expression of HSP70 and grp94 in 78 human esophageai cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis. RESULTS: Both esophageai cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageai carcinoma, 95.0%(72/78) showed positive HSP70, mainly stained in nuclei, while grp94 was mainly stained in cell plasma, and the positive rate was 71.8% (56/78).There was a significant difference in the expression of HSP70 and grp94 between esophageai cancer and adjacent normal tissues (P<0.01). Compared with adjacent normal tissues, there was a significant difference between differential types and HSP70 expression (P<0.01). CONCLUSION: HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70 is related to the differentiation of esophageai carcinoma.     

高危型HPV感染与宫颈癌组织中IDO表达的相关性研究

目的探讨吲哚胺2,3-二氧酶（IDO）在宫颈癌发生发展中的作用及其与高危型人乳头状瘤病毒（HR—HPV）感染之间的关系。方法我院经宫颈活检病理确诊为CINⅢ和宫颈浸润癌患者43例,同时期因子宫肌瘤行全子宫切除宫颈正常患者30例作为对照。采用第2代杂交捕获法（HC-2）HR-HPVDNA检测高危型HPV DNA,免疫组化染色方法检测IDO的表达。结果IDO和HR—HPV阳性率在宫颈原位癌和浸润癌组均显著高于正常宫颈组（P〈0．01）。HR—HPV感染与IDO表达呈正相关（rs=0．759,P〈0．01）。结论在HR—HPV感染的CINⅢ和宫颈浸润癌中,IDO出现过表达,可能与肿瘤免疫逃逸有关。IDO可能成为宫颈癌预后的预测因子及治疗靶点。     

宫颈鳞癌组织中pSTAT3、Cyclin D1、VEGF表达变化及意义

目的 观察宫颈鳞癌组织中磷酸化信号转导和转录激活因子3 （pSTAT3）、细胞周期素D1（Cyclin D1）及血管内皮生长因子（VEGF）蛋白的表达变化,并探讨其临床意义.方法 采用免疫组化SP法检测40例宫颈鳞癌（癌症组）、20例宫颈上皮内瘤变（CIN组）和15例正常宫颈鳞状上皮（对照组）组织中的pSTAT3、Cyclin D1和VEGF蛋白.结果 在癌症组及CIN组,pSTAT3过表达率分别为20.0％、62.5％ （P ＜0.05）,Cyclin D1过表达率分别为30.0％、72.5％ （P ＜0.05）,VEGF过表达率分别为40.0％、82.5％（P＜0.05）;对照组均无过表达者.pSTAT3、Cyclin D1蛋白过表达与宫颈鳞癌病理分级、临床分期及淋巴结转移有关（P均＜0.05）,VEGF蛋白过表达与宫颈鳞癌病理分级、淋巴结转移有关（P均＜0.05）.宫颈鳞癌组织中,pSTAT3与Cyclin D1及VEGF蛋白过表达呈正相关（r分别为0.531、0.618,P均＜0.05）.结论 宫颈鳞癌组织中pSTAT3、Cyclin D1及VEGF蛋白表达增高,三者共同参与了宫颈鳞癌的发生、发展.     

A research for the relationship between human papillomavirus and human uterine cervical carcinoma

Summary Biopsies from 318 cases with squamous cell carcinoma of the uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 with normal cervical epithelium were collected from different geographic regions with different cervical cancer mortalities. The DNA · DNA dot-blot and Southern blot hybridization results show that there is a close relationship between HPV-16 and the uterine cervical squamous cell carcinoma in China. One very interesting observation is that the finding of HPV-16-homologous DNA differs significantly among five geographic regions, and corresponds with the mortalities from cervical cancer of these five regions. HPV-11 was found mainly in benign lesions. The rate of detection of HPV-16 in Chinese women increased from 8.3% in normal cervical epithelium to 20% in chronic cervicitis, 28% in cervical condyloma, 50% in CIN and 60.4% in cervical cancer. It is suggested that HPV-16 infection may be an etiological factor in the development of human cervical carcinoma. From the results of Southern blot hybridization, it appeared that HPV-16 DNA had been integrated into the genome of the host cell in cervical cancer. Whereas the HPV-16 DNA sequence was only present as an episome in normal cervical epithelium and cervical benign lesions. The rate of occurence of E6-E7 genes is the highest (88.9%) compared with that of other subgenomic fragments of HPV-16 in specimens of human cervical cancer in China. This implies that E6 and E7 may be the oncogenic genes of HPV-16 and play an important role in the carcinogenesis of human cervical epithelial cells. The amplification and rearrangement of the c-myc protooncogene are closely associated with the occurrence of cervical cancer. The results presented here revealed that the activated c-myc oncogene may cooperate with HPV-16 in the carcinogenic processes.Abbreviations HPV Human papillomavirus - CIN cervical intraepithelial neoplasia - SSC standard saline citrate     

Over-expression of protein kinase C isoforms (α, δ, θ and ζ) in squamous cervical cancer

Protein kinase C was found to be significantly over-expressed in cancer samples compared to adjacent normal cervical tissues by proteomics in our previous study. The aim of this study was to examine protein kinase C expression and to analyze the expression patterns of protein kinase C isoforms in squamous cervical cancer at the protein levels and their associations with clinical and pathologic factors of squamous cervical cancer. First, Western blotting was used to examine protein kinase C expression in the specimens of tumors and matched adjacent normal tissues which were collected from 12 patients with squamous cervical cancer. Protein kinase C isoforms (α, δ, θ and ζ) expression were then detected by immunohistochemistry in other 43 cases of squamous cervical cancer tissues, 32 cases of corresponding adjacent normal cervical squamous epithelial tissue and 31 cases of cervical intraepithelial neoplasia. Western blot analysis revealed that protein kinase C expression was positive in squamous cervical cancer while it was not expressed in normal cervical tissues. On the other hand, immunohistochemical analysis suggested that, protein kinase C isoforms (α, δ, θ and ζ) expression was significantly higher in squamous cervical cancer compared to cervical intraepithelial neoplasia, as well as in cervical intraepithelial neoplasia compared with normal tissues, respectively.High levels of protein kinase C α expression were associated with cellular differentiation(P<0.05). Protein kinase C δ was significantly associated with tumor stage (P<0.05) and protein kinase C ζ was associated with lymphatic metastasis (P < 0.05). These findings indicate that protein kinase C isoforms expression in cervical lesions was associated with carcinogenesis and might play important roles throughout the process of cervical cancer development.     

Galectin-9 expression links to malignant potential of cervical squamous cell carcinoma

Purpose  Galectin-9 (Gal-9) induces adhesion and aggregation of certain cell types and can be a prognostic factor in the patients with melanoma and breast cancer. We assessed the experiments to resolve whether Gal-9 expression in cervical neoplasm links to malignant potential of cervical squamous cell carcinoma (SCC) cells. Methods  Gal-9 expression was examined with immunohistochemical techniques in 23 normal cervical squamous epithelia, 17 cervical intraepithelial neoplasia (CIN), and 38 cervical SCC compared to E-cadherin. CIN was divided into low-grade and high-grade squamous intraepithelial lesions (8 LSIL and 9 HSIL), and SCC was into well-, moderately and poorly differentiated SCC (6 WSCC, 20 MSCC and 12 PSCC). Results  Gal-9 and E-cadherin were evidently detected in normal epithelium and endocervical glands, but those in CIN and SCC were significantly faint. Moreover, both the Gal-9 and E-cadherin expressions in HSIL were significant lower than those in LSIL, suggesting their association with malignant transformation. Unexpectedly, Gal-9 and E-cadherin in WSCC were significantly high compared to those in HSIL. Furthermore, those in SCC were inversely correlated with the grade of differentiation (WSCC >> MSCC >> PSCC), implying the possible involvement of Gal-9 and E-cadherin in the differentiation of SCC. In contrast, they were not different among the FIGO stage. Gal-9 expression was well correlated with E-cadherin expression in CIN and SCC but not in normal cervical epithelia. Conclusion  The present results suggest that decreased Gal-9 expression is inversely associated with malignant potential or differentiation of cervical CIN and SCC as a differentiation biomarker.     

DAPK1、ERα、HLA-Ⅰ基因蛋白表达水平与宫颈病变病理进程的相关性

目的从蛋白质水平观察死亡相关蛋白激酶(DAPK1)、人类白细胞抗原-Ⅰ(HLA-Ⅰ)、雌激素受体(ER)α基因表达水平与不同病理级别的宫颈病变的相关性。方法收集汉族妇女宫颈炎、宫颈上皮内瘤样病变(CIN)和宫颈鳞癌患者石蜡包埋组织标本115例,采用免疫组织化学方法鉴定蛋白表达水平。结果 DAPK-1、ERα、HLA-Ⅰ基因在宫颈炎/CINⅠ组织中阳性表达率分别为90%、76%、88%;在CINⅡ/Ⅲ和宫颈鳞癌中这些基因阳性表达率分别为53%、48%;45%、24%;67%、40%。在CINⅡ/Ⅲ和宫颈鳞癌中这些基因阳性表达率明显低于宫颈炎/CINⅠ,各组阳性表达率差异显著(P<0.05),随着宫颈病变病理变化的加重,基因蛋白阳性表达率逐渐降低。结论 DAPK1、HLA-Ⅰ、ERα基因表达阳性或缺失可能是CIN及宫颈鳞癌的重要生物学特征,与宫颈癌发生关系密切,这些基因的检测可能作为预测CIN和宫颈癌的重要生物指标。