Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.
Adult ; Aged ; Carcinoma/metabolism* ; Carcinoma/drug therapy* ; Cervix Neoplasms/metabolism* ; Cervix Neoplasms/drug therapy* ; Female ; Human ; Middle Age ; Neoadjuvant Therapy* ; Receptor, Epidermal Growth Factor/metabolism* ; Receptor, erbB-2/metabolism* ; Treatment Outcome

Human papilloma virus (HPV) is believed to be an essential factor for the development of cervical cancer. Early diagnosis and treatment of cervical intraepithelial neoplasia can effectively inhibit the future progression. HPV late 1 protein possesses epitope that can identify and adhere to host cells, and thus may play an important role in HPV infection and cervical carcinogenesis.
Capsid Proteins ; Cervix Uteri ; metabolism ; virology ; Female ; Humans ; Oncogene Proteins, Viral ; Papillomavirus Infections ; complications ; Uterine Cervical Neoplasms ; virology

The purpose of this study was to investigate the implications of dietary intake and the level of plasma antioxidant, lipid peroxidation, and antioxidant capacity in Korean women with cervical intraepithelial neoplasia (CIN). From October 2002 to March 2003, 58 patients diagnosed with CIN (confirmed with colposcopy directed biopsy) and 86 patients without any cervical disease as control group were enrolled in the study at the Department of Gynecology cancer center at Samsung Cheil Hospital. The intake of antioxidant vitamins in both groups exceeded the amount recommended by the Korea RDA, 7th edition. The plasma concentration of Vitamin C was significantly lower in the CIN group (0.36 mg/dL) than in the control group (0.48 mg/dL) (p<0.05). The two groups showed similar plasma concentrations of beta-carotene, alpha-tocopherol, and retinol. The average concentration of malondialdehydes in the CIN group, 7.23 mmol/mL, was significantly higher than in the control group, 5.18 mmol/mL (p<0.01). The total radical trapping antioxidant potential concentration of plasma was significantly higher in the CIN group (1.15 mM) than in the control group (1.25 mM) (p<0.05). These results suggest that there is a possible correlation between cervical intraepithelial neoplastic processes and changes in the plasma antioxidative system.
Adult ; Aged ; Antioxidants/administration & dosage/*metabolism ; Cervical Intraepithelial Neoplasia/*metabolism ; Cervix Neoplasms/*metabolism ; Energy Intake ; Female ; Humans ; *Lipid Peroxidation ; Middle Aged ; Vitamins/administration & dosage/*blood

OBJECTIVETo investigate PTEN expression and mutation status in the development of cervical adenocarcinoma.

METHODSImmunohistochemistry study of PTEN protein was performed on 42 cases of cervical adenocarcinoma, 20 cases of cervical glandular intraepithelial neoplasia and 28 cases of normal cervix tissue samples. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to detect the presence of mutation of exons 5 and 8 of PTEN gene.

RESULTSPositive expression rates of PTEN protein were 54.8% (23/42), 25.0% (5/20) and 100% (28/28) in cervical adenocarcinoma, cervical glandular intraepithelial neoplasia and normal cervix tissues, respectively. There were significant differences among the 3 groups (P < 0.05). Positive expression rates of PTEN protein were 47.4% (9/19), 20.0% (2/10) and 92.3% (12/13) in mucinous, endometrioid and the other variants of cervical adenocarcinoma, respectively. Mutation rates at exon 5 and exon 8 of PTEN gene were 19.0% (8/42), 45.0% (9/20) and 0 in cervical adenocarcinoma, cervical glandular intraepithelial neoplasia and normal cervix tissue, respectively. There were significant differences among 3 groups (chi(2) = 4.29, chi(2) = 12.70; P < 0.05). The mutation rates were 21.1% (4/19) and 40.0% (4/10) in mucinous and endometrioid variants of cervical adenocarcinoma, respectively. There was no mutation at exons 5 and 8 of PTEN gene detected in other variants of cervical adenocarcinoma.

CONCLUSIONThe development of cervical adenocarcionomas is correlated with the mutation and absence of the protein expression of PTEN, likely in the early phase of their carcinogenesis.

Adenocarcinoma ; genetics ; metabolism ; Adenocarcinoma, Mucinous ; genetics ; metabolism ; Carcinoma, Endometrioid ; genetics ; metabolism ; Cervical Intraepithelial Neoplasia ; genetics ; metabolism ; Cervix Uteri ; metabolism ; Exons ; Female ; Humans ; Mutation ; PTEN Phosphohydrolase ; genetics ; metabolism ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Uterine Cervical Neoplasms ; genetics ; metabolism

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

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

The superoxide anion, hydrogen peroxide, and hydroxyl radical are oxygen free radicals which arise in cell metabolism and which are toxic to cells, with an important role in carcinogenesis. The measurement of the oxygen free radical is a problem due to the instantaneously changing nature, and therefore the superoxide dismutase(SOD) is employed which act as an oxygen free radical scavenger. The authors quantitatively analyzed the SOD levels in normal uterine cervix epithelium, cervical intraepithelial neoplasia, and in invasive cervical cancer patients by the SOD-525R spectrophotometric assay and compared the results between each group with respect to prognostic variables such as stage of disease, cell type, lymph node involvement, and SCC Ag(TA-4 Ag) levels. The mean SOD levels were 0.41U/ml, 0.39U/ml and 0.73U/ml in the normal uterine cervix, intraepithelial neoplasia, and invasive cervical cancer groups, respectively, showing statistically significant difference by the Oneway anova test(p=0.05). The mean SOD levels according to the stage of disease were 0.5U/ml, 0.62U/ml, and 1. 15U/ml for stages I a, I b, and stage II and above(p=0.029). For the cell type the SOD levels were 0.77/ml for squamous cell carcinoma and 0.57U/ml for adenocarcinoma(p=0.15). For cancer cell lymph node involvement cases, the mean SOD levels were 0.75U/ml and 0.57U/ml for lymph node involvement and no involvement respectively(p=NS). The mean SOD levels also did not show any significance when compared with SCC Ag levels where SOD was 0.78U/ml for SCC Ag levels of more than 2.0ng/ml, and 0.77U/ml for SCC Ag levels of less than 2.0ng/ml. From the above results the authors conclude that SOD levels were higher in invasive cervical cancer tissues compared to intraepithelial neoplasia and normal cervical tissues, that SOD levels increased with higher stage of disease, and that there was no relationship between SOD levels and known prognostic variables such as cell type, lymph node involvement and SCC Ag level.
Carcinogenesis ; Carcinoma, Squamous Cell ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Epithelium ; Female ; Free Radicals ; Humans ; Hydrogen Peroxide ; Hydroxyl Radical ; Lymph Nodes ; Metabolism ; Oxygen* ; Superoxides* ; Uterine Cervical Neoplasms

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

We investigated the relationship between vascular endothelial growth factor (VEGF) expression and clinical outcome in squamous cell carcinoma of the cervix treated with radiotherapy alone. The immunohistochemical study was performed for fortytwo paraffin embedded specimens with anti-VEGF mouse monoclonal antibody. Staining was defined as positive for VEGF when more than 10% of the tumor cells were stained from 500 cells counted. Positive VEGF expression was observed in twenty-one among forty-two patients. VEGF expression according to stage (p=0.101), lymph node status (p=0.621), parametrial invasion (p=0.268), and age (p=0.5) revealed no significant difference. But the VEGF expression was significantly higher in tumors larger than 4 cm (p=0.031). Five year survival rates according to VEGF expression status were 89% for VEGF negative group and 47% for VEGF positive group (p=0.02). FIGO stage (p=0.007), tumor size (p=0.025) and the duration of external beam radiation therapy (p=0.006) were also significant prognostic factors for overall survival. We suggest that VEGF expression may be a prognotic factor of the cervix cancer patients treated with radiation therapy alone.
Carcinoma, Squamous Cell/*metabolism/mortality/*radiotherapy ; Cervix Neoplasms/*metabolism/mortality/*radiotherapy ; Female ; Humans ; Immunohistochemistry ; Predictive Value of Tests ; Prognosis ; Regression Analysis ; Survival Rate ; Tumor Markers, Biological/metabolism ; Vascular Endothelial Growth Factor A/*metabolism

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