1.Expression and clinicopathologic significance of Furin in cervical carcinomas.
Leilei ZHANG ; Zhulei SUN ; Qiang LIU ; Yan ZHANG ; Hong JING ; Jiang WU
Chinese Journal of Pathology 2014;43(1):36-37
Adult
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Aged
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Cervical Intraepithelial Neoplasia
;
metabolism
;
pathology
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Cervix Uteri
;
metabolism
;
pathology
;
Disease Progression
;
Female
;
Furin
;
genetics
;
metabolism
;
Humans
;
Matrix Metalloproteinase 14
;
metabolism
;
Middle Aged
;
RNA, Messenger
;
metabolism
;
Uterine Cervical Neoplasms
;
metabolism
;
pathology
;
Vascular Endothelial Growth Factor C
;
metabolism
;
Young Adult
2.Correlation of HIPK2 expression with HPV infection and apoptosis in cervical cancer.
Mariam A M AL-BEITI ; Xin LU ; Xi-Shi LIU
Chinese Journal of Oncology 2009;31(6):434-437
OBJECTIVETo evaluate the correlation of the expression of homeodomain-interacting protein kinase 2 (HIPK2) with human papillomavirus (HPV) infection and apoptosis in cervical cancer.
METHODSFormalin-fixed, paraffin embedded tissue samples from 50 cervical cancers and 15 normal uterine cervix cases were obtained. Apoptosis was quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay and the expression of HIPK2 as well as HPV by immunohistochemical staining.
RESULTSHIPK2 protein expression was detected in 88.0% (44/50) of cervical cancers and 6.7% (1/15) of normal cervical tissues. HPV was found in 78.0% (39/50) of cervical cancers and 20.0% (3/15) of normal cervical tissue samples. The expression of HIPK2 protein was significantly and positively correlated with HPV presence (r=0.467, P<0.01), but negatively with apoptotic index (r=-0.370, P<0.05).
CONCLUSIONHIPK2 protein expression is positively correlated with HPV infection, but negatively with apoptotic index in cervical cancers. Therefore, HIPK2 may be involved in the mechanism of apoptosis in cervical cancer and may play an important role in cervical carcinogenesis.
Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Carrier Proteins ; metabolism ; Cervix Uteri ; metabolism ; Female ; Humans ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology
3.Identification of miR-23a as a novel microRNA normalizer for relative quantification in human uterine cervical tissues.
Yuanming SHEN ; Yang LI ; Feng YE ; Fenfen WANG ; Xiaoyun WAN ; Weiguo LU ; Xing XIE
Experimental & Molecular Medicine 2011;43(6):358-366
Quantitative real-time RT-PCR (RT-qPCR) is being widely used in microRNA expression research. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in microRNA RT-qPCR studies. The aim of this study was to identify the most stable reference gene(s) for quantification of microRNA expression analysis in uterine cervical tissues. A microarray was performed on 6 pairs of uterine cervical tissues to identify the candidate reference genes. The stability of candidate reference genes was assessed by RT-qPCR in 23 pairs of uterine cervical tissues. The identified most stable reference genes were further validated in other cohort of 108 clinical uterine cervical samples: (HR-HPV- normal, n = 21; HR-HPV+ normal, n = 19; cervical intraepithelial neoplasia [CIN], n = 47; cancer, n = 21), and the effects of normalizers on the relative quantity of target miR-424 were assessed. In the array experiment, miR-26a, miR-23a, miR-200c, let-7a, and miR-1979 were identified as candidate reference genes for subsequent validation. MiR-23a was identified as the most reliable reference gene followed by miR-191. The use of miR-23a and miR-191 to normalize expression data enabled detection of a significant deregulation of miR-424 between normal, CIN and cancer tissue. Our results suggested that miR-23a and miR-191 are the optimal reference microRNAs that can be used for normalization in profiling studies of cervical tissues; miR-23a is a novel microRNA normalizer.
Cervical Intraepithelial Neoplasia/diagnosis/genetics/*metabolism/pathology
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Cervix Uteri/*metabolism/pathology
;
Early Detection of Cancer
;
Female
;
Gene Expression Profiling/*standards
;
Humans
;
MicroRNAs/genetics/*metabolism/standards
;
Microarray Analysis
;
Reference Standards
;
Reverse Transcriptase Polymerase Chain Reaction
;
Uterine Cervical Neoplasms/diagnosis/genetics/*metabolism/pathology
4.Mesonephric hyperplasia in uterine cervix: report of two cases.
Yu ZENG ; Yunjin WU ; Xuyou ZHU ; Suxia ZHANG ; Pan GU ; Hailong ZHU ; Weizhe QIU ; Xianghua YI
Chinese Journal of Pathology 2014;43(5):339-340
Adenocarcinoma
;
metabolism
;
pathology
;
Adenocarcinoma, Clear Cell
;
metabolism
;
pathology
;
Adult
;
Carcinoma, Endometrioid
;
metabolism
;
pathology
;
Cervix Uteri
;
metabolism
;
pathology
;
surgery
;
Cyclin-Dependent Kinase Inhibitor p16
;
metabolism
;
Diagnosis, Differential
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Electrosurgery
;
Endometrial Neoplasms
;
metabolism
;
pathology
;
Female
;
Humans
;
Hyperplasia
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Keratin-7
;
metabolism
;
Mesonephros
;
metabolism
;
pathology
;
surgery
;
Neprilysin
;
metabolism
;
Uterine Cervical Neoplasms
;
metabolism
;
pathology
5.Placental site trophoblastic tumor occurring in uterine cervix: report of a case.
Yan-mei HE ; Xian-ying YAO ; Kai-xuan YANG
Chinese Journal of Pathology 2009;38(9):631-632
Adult
;
Alkaline Phosphatase
;
metabolism
;
Carcinoma, Squamous Cell
;
metabolism
;
pathology
;
Cervix Uteri
;
metabolism
;
pathology
;
surgery
;
Choriocarcinoma
;
metabolism
;
pathology
;
Chorionic Gonadotropin
;
metabolism
;
Diagnosis, Differential
;
Female
;
GPI-Linked Proteins
;
metabolism
;
Humans
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Hysterectomy
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Placental Lactogen
;
metabolism
;
Pregnancy
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Trophoblastic Tumor, Placental Site
;
metabolism
;
pathology
;
surgery
;
Uterine Cervical Neoplasms
;
metabolism
;
pathology
;
surgery
6.Expression of MIF, VEGF and p16 proteins and their correlation with clinicopathological features in cervical cancer.
Wen LI ; Mian HE ; Jian-Fang ZENG ; Jin-Tang XIA ; Lian-Zhou CHEN ; Yang CHEN ; Jun-Xiu LIU
Chinese Journal of Oncology 2008;30(7):511-514
OBJECTIVETo investigate the expression of macrophage migration inhibitory factor (MIF), p16 and vascular endothclial growth factor (VEGF) proteins and their relationship with clinicopathological features in cervical cancer.
METHODSTissue microarray (TMA) and immunohistochemistry were used to detect the expression of MIF, p16 and VEGF proteins in specimens of 10 normal cervical epithelial tissues, 18 cervical intraepithelial neoplasia (CIN II, III) and 31 cervical squamous cell carcinomas. Western blotting was used to detect the expression of MIF, p16 and VEGF proteins in fresh samples of 3 normal cervical epithelial tissues, 3 CIN (III) and 6 cervical squamous cell carcinomas (3 Ib and 3 IIb).
RESULTSPositive expression rates of MIF were 0, 72.2% and 93.5% in the normal, CIN and carcinoma samples, 20.0%, 33.3% and 71.0% for p16, and 10.0%, 44.4% and 74.2% for VEGF, respectively. The expression rates and levels of the three genes were significantly higher in cervical carcinomas than those in CIN. MIF expression was significantly higher in the cases with lower differentiation (17 cases, P = 0.021), and was positively correlated with VEGF expression (P = 0.0045). VEGF expression rate was significantly higher in both cases of poorly differentiated carcinomas and those with stage II b carcinoma or beyond (P = 0.004, P = 0.008). p16 expression was not found to be correlated with tumor differentiation or clinical stage. It was showed by Western blotting that the expression levels of MIF, VEGF and p16 were significantly higher in the carcinomas than those in CIN or normal tissues.
CONCLUSIONExpression of MIF, VEGF and p16 are probably involved in the process of cervical carcinogenesis. MIF expression is correlated with tumor differentiation. VEGF expression is correlated with both tumor differentiation and clinical stage.
Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intramolecular Oxidoreductases ; metabolism ; Macrophage Migration-Inhibitory Factors ; metabolism ; Neoplasm Proteins ; metabolism ; Neoplasm Staging ; Uterine Cervical Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism
7.Diagnosis and differential diagnosis of cervical intraepithelial neoplasias and related disease.
Chinese Journal of Pathology 2007;36(8):563-566
Cervical Intraepithelial Neoplasia
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diagnosis
;
metabolism
;
pathology
;
Cervix Uteri
;
metabolism
;
pathology
;
Cyclin-Dependent Kinase Inhibitor p16
;
metabolism
;
Diagnosis, Differential
;
Female
;
Humans
;
Ki-67 Antigen
;
metabolism
;
Membrane Proteins
;
metabolism
;
Neoplasm Invasiveness
;
Uterine Cervical Dysplasia
;
diagnosis
;
metabolism
;
pathology
;
Uterine Cervical Neoplasms
;
diagnosis
;
metabolism
;
pathology
8.Expression and clinical significance of HMGB1 and RAGE in cervical squamous cell carcinoma.
Quan HAO ; Xiao-Qin DU ; Xin FU ; Jing TIAN
Chinese Journal of Oncology 2008;30(4):292-295
OBJECTIVETo investigate the association between high mobility group box1 (HMGB1) and cervical squamous cell carcinoma (CSCC), and explore the role of HMGB1/RAGE pathway in the metastasis of CSCC.
METHODSLevels of HMGB1 mRNA and RAGE mRNA in CSCC and normal cervical tissues were detected by real time quantitative polymerase chain reaction (qRT-PCR), and the level of HMGB1 protein was determined by immunohistochemistry and Western blotting.
RESULTSThe mRNA and protein expression of HMGB1 was significantly higher in CSCC than that in normal cervical tissue (P < 0.05), correlated with stage, invasion and metastasis (P < 0.05), but not with tumor size and differentiation (P > 0.05). The levels of RAGE mRNA and HMGB1 mRNA were both significantly higher (r = 0.663, P < 0.05) in metastatic CSCC in comparison with those in the non-metastatic cases.
CONCLUSIONHMGB1 is involved in the invasion and metastasis of CSCC, and HMGB1/RAGE pathway plays an important role in the metastasis of CSCC.
Blotting, Western ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; HMGB Proteins ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Uterine Cervical Neoplasms ; metabolism ; pathology
9.Expressions of bFGF and PTEN in cervical carcinoma and their clinical significance.
Chun-fang LUO ; Hui-li HONG ; Yu-lan LU ; Hui WANG ; Ming-qiu LIU
Chinese Journal of Oncology 2010;32(7):533-538
OBJECTIVETo investigate the expressions of bFGF and PTEN in cervical carcinoma and their clinical significance.
METHODSTissue microarray technique and immunohistochemistry SP method were used to detect the expressions of bFGF and PTEN in 143 cases of invasive carcinoma of cervix (ICC) and 20 cases of normal cervical epithelium remote from tumor (NCE). The relationship between the expressions of bFGF and PTEN in ICC and some factors relating to clinical pathology of cervical carcinoma such as histopathological grading, lymph node metastasis, stroma involvement and FIGO staging were analyzed.
RESULTSThe rate of the positive expression of bFGF in ICC was significantly higher than that in NCE 88.8% (127/143) vs. 25.0% (5/20, P = 0.000). The rate of positive expression of PTEN in ICC was significantly lower than that in NCE 67.1% (96/143) vs. 100.0% (20/20, P = 0.000). The expression of bFGF was positively correlated with lymph node metastasis and histopathological grading (r = 0.239, P = 0.004 and r = 0.369, P = 0.000, respectively). The expression of PTEN was negatively correlated with FIGO staging, histopathological grading and lymph node metastasis (r = -0.189, P = 0.024; r = -0.211, P = 0.011; r = -0.321, P = 0.000, respectively). The expression of bFGF was negatively correlated with the expression of PTEN in ICC (r = -0.261, P = 0.002).
CONCLUSIONThe overexpression of bFGF and underexpression of PTEN are closely related to the invasion and growth of cervical carcinoma. Detection of the expression of both bFGF and PTEN may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.
Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervix Uteri ; cytology ; metabolism ; Epithelium ; metabolism ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; PTEN Phosphohydrolase ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; Young Adult
10.Identification of Gene Expression and Gene Ontology Classification by Differential Display RT-PCR in Human Cervical Squamous Cell Carcinoma.
Min Je SEO ; Su Mi BAE ; Kyoung Mi PARK ; Byung Hoon KIM ; Yong Wan KIM ; Kyuong Yun SEO ; Kyung A SEO ; Yong Wook KIM ; Soo Young HUR ; Duck Young RO ; Joon Mo LEE ; Sung Eun NAMKOONG ; Chong Kook KIM ; Woong Shick AHN
Korean Journal of Obstetrics and Gynecology 2004;47(4):684-694
OBJECTIVE: The molecular pathology of cervical cancer associated with human papillomavirus infection is presently unclear. In an effort to clarify the multiple interactions of a number of genes involved in cervical carcinogenesis, the gene expression profiles and pathogenic cellular processes between human cervical squamous cell carcinoma and normal cervix were investigated by mRNA differential display and the Gene Ontology analysis. METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The squamous cell carcinoma tissue samples of 3 patients invasive cancer stage II (1), IV (2) were investigated by mRNA differential display. As a control, we used a common reference that was mixed with equal amount of RNA obtained from 17 normal cervix to obtain variation- independent control. Also, we constructed hierarchical functional structures using gene ontology. Then, the specific function groups were correlated with differential gene expression profiles. In addition, specific gene expression patterns in several tissue samples were investigated by using DDRT-PCR analysis. RESULTS: Differentially expressed 191 genes were identified in tumor samples. Of these genes, 128 were up-regulated and 63 were down-regulated above 1.5-fold. The gene expression profiles were classified into 46 mutually dependent function sets and organized into sub-function sets depending on the cervical cancer pathway, suggesting the potentially significant genes of unknown function affected by carcinogenesis pathway. The genes related to metabolism, signal transduction, and chaperon activity were significantly up-regulated. In contrast, significant down-regulations were shown in nucleic acid binding activity, tumor suppressor and structural activity. Reliable gene expression data shows the validation of profiling method for studying the cervical cancer-specific pathway. CONCLUSION: The specific functions assigned to each expressed gene were correlated with gene ontology for the establishment of a powerful cervical carcinogenesis pathway. The results suggest that the differentially regulated cellular process profiles have an important impact on discovery of pathogenic pathway in human cervical squamous cell carcinoma and provide the potentially significant genes of unknown function. Also, the gene ontology analysis can overcome the complexity of the expression profiles of mRNA differential display via a cellular process level approach. Thereby, a valuable prognostic candidate gene with real relevance to disease-specific pathogenesis can be found at the cellular process levels.
Biopsy
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Carcinogenesis
;
Carcinoma, Squamous Cell*
;
Cervix Uteri
;
Classification*
;
Female
;
Gene Expression Profiling
;
Gene Expression*
;
Gene Ontology*
;
Gynecology
;
Humans*
;
Korea
;
Metabolism
;
Obstetrics
;
Papillomavirus Infections
;
Pathology, Molecular
;
RNA
;
Signal Transduction
;
Transcriptome
;
Uterine Cervical Neoplasms