Adult ; Aged ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; 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

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 ; Electrosurgery ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyperplasia ; Keratin-7 ; metabolism ; Mesonephros ; metabolism ; pathology ; surgery ; Neprilysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology

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 ; 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

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

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

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 ; Hysterectomy ; Placental Lactogen ; metabolism ; Pregnancy ; Trophoblastic Tumor, Placental Site ; metabolism ; pathology ; surgery ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery

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

OBJECTIVETo analyze the characteristics of cervical minimal deviation adenocarcinoma (MDA) and the methods of diagnosis and treatment.

METHODSA retrospective study was carried out to evaluate the clinical and pathological data of 15 patients with MDA treated from 1992 to 2007.

RESULTSThe average age of the 15 patients was 42.3 years. The main symptoms were increased discharge and irregular vaginal bleeding. Preoperative Pap smears showed adenocarcinoma in 3 cases (27.3%). The diagnosis of MDA was confirmed in 8 cases by cervical punch biopsies (53.3%) and 2 cases by conization. Several cysts were noted in sections of the endocervix. Microscopic examination showed glands irregular in size and shape. However, the deviation of tumor cells was minimal. Immunohistochemistry revealed positive expression of CEA and alpha-SMA. The mean follow-up time was 51.0 months. The overall 5-year survival rate was 85.7%. Four cases experienced recurrence in the vagina and pelvis at 2 years after operation. Three cases died of the disease relapse with an average survival time of 36.3 months.

CONCLUSIONCervical minimal deviation adenocarcinoma is rare, with minimal deviation of cell shape from the normal cervical cells and difficult in diagnosis. A deep biopsy or conization is necessary when punch biopsy is not sufficient for diagnosis. Immunohistochemistry is helpful to make an accurate diagnosis. Surgery is the first choice for cervical minimal deviation adenocarcinoma. Radiotherapy and/or chemotherapy should be given if needed. The prognosis can be improved if a proper treatment plan is carried out.

Actins ; metabolism ; Adenocarcinoma ; diagnosis ; pathology ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoembryonic Antigen ; metabolism ; Cervix Uteri ; pathology ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Conization ; Epirubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Papanicolaou Test ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; therapy ; Vaginal Smears

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

Cervical Intraepithelial Neoplasia ; 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