Cell Carcinoma Of Uterine Cervix Research Articles

Concurrent high expression of human telomerase reverse transcriptase and human nonmetastatic clone 23 in high-grade squamous intraepithelial neoplasia and squamous cell carcinoma of uterine cervix

Human telomerase reverse transcriptase (hTERT) and human nonmetastatic clone 23 (nm23-H1) may be separately involved in tumor progression of uterine cervix. We therefore investigate the correlations of hTERT and nm23-H1 in cervical carcinogenesis and further check their application. One hundred and twenty-eight cervical tissues, including 48 squamous cell carcinoma (SCC), 36 high-grade cervical intraepithelial neoplasia (CIN) (CIN 2 and CIN 3), 20 low-grade CIN 1, and 24 normal cases, were collected for immunohistochemical expression of hTERT and nm23-H1. Spearman rank correlation analysis was applied to assess their correlation in these samples. The Fisher exact or Chi-square test was used to evaluate the expression of hTERT or nm23-H1 among each subgroup. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy of hTERT and/or nm23-H1 were calculated for the prediction of high-grade CIN and SCC. We found normal cervix and CIN 1 samples had concurrent low expression of hTERT and nm23-H1, whereas high-grade CIN and SCC samples had concurrent high immunoreactivities. The hTERT alone and hTERT or nm23-H1 in combination had better sensitivity, NPV, and accuracy. The nm23-H1 alone as well as hTERT and nm23-H1 in combination had better specificity and PPV. Our results reveal a significantly positive relationship between expression of hTERT and nm23-H1 in normal and neoplastic tissues of uterine cervix. We suggest high expression of hTERT alone and hTERT or nm23-H1 in combination can be offered additional molecular information correlated with high-grade CIN and SCC.

Increased expression level of squamous cell carcinoma antigen 2 and 1 ratio is associated with poor prognosis in early-stage uterine cervical cancer

Squamous cell carcinoma antigen (SCCA) is a tumor marker for patients with squamous cell carcinoma of uterine cervix, lung, and esophagus. It was encoded by two highly homologous genes, SCCA1 and SCCA2. However, the relevance of SCCA genes to squamous cell carcinogenesis and patient outcome remains far from clear. In this study, by using laser microdissection and real-time quantitative polymerase chain reaction procedures, the messenger RNA (mRNA) expression of the SCCA1 and SCCA2 genes in normal, dysplastic, and malignant squamous epithelia from uterine cervical tissues were analyzed and correlated with outcome of cancer patients. We found that the SCCA2/A1 mRNA ratios were progressively increased from normal, dysplastic, to cancer cells, and the mean ratio was significantly higher in cancer tissues than that in normal epithelium (P= 0.02). The SCCA2/A1 mRNA ratios were not significantly associated with types of human papillomavirus infection (P > 0.05). High SCCA2/SCCA1 mRNA ratios (ratio >1) were an independent predictor of disease recurrence (relative risk: 3.58; P= 0.003). Of the 38 patients with cervical cancer, 12 patients with high SCCA2/SCCA1 mRNA ratios had a significant lower 2-year disease-free survival of only 50%, while it was 92% in those with low SCCA2/SCCA1 mRNA ratios (P < 0.001). In conclusion, our study indicated that the ratios of SCCA2 to SCCA1 RNA were increased during the process of cervical carcinogenesis, and patients with elevated SCCA2/A1 ratio carried a higher risk for recurrence in early-stage uterine cervical cancer.

Promoter hypermethylation and loss of heterozygosity of FHIT genes in squamous cell carcinoma of uterine cervix

Objective : This study was to investigate the status of hypermethylation and loss of heterozygosity (LOH) in chromosome 3p tumor-suppressor gene for cervical carcinoma. Methods : We examined the promoter methylation status of the chromosome 3p gene, fragile histidine triad (FHIT), in 37 samples of cervical squamous cell carcinoma and corresponding noncancerous tissues using a methylation-specific polymerase chain reaction. We also analyzed the 37 paired samples for LOH at two loci on chromosome 3p. Results : Promoter hypermethylation in FHIT was detected in 24% of tumors, whereas no hypermethylation was detected in the corresponding noncancerous tissues. LOH in the regions of FHIT was observed in 10% of informative cases. There were no correlations between LOH and promoter hypermethylation for the gene. FHIT hypermethylation was associated with small tumors and, when adjusted for tumor size, correlated significantly with more frequent lymph node metastasis. Conclusion : Promoter hypermethylation and LOH of FHIT gene may play a role in cervical carcinogenesis. In addition, hypermethylation of FHIT may be associated with the status (aggressiveness) of cervical carcinoma.

DNA Hypomethylation of CAGE Promotors in Squamous Cell Carcinoma of Uterine Cervix

This study was performed to determine whether promotor hypomethylation of CAGE is involved in cervical carcinogenesis. The surgical specimens of 40 cervical squamous cell carcinoma patients treated at Seoul National University Hospital and those of 48 healthy controls were used, with informed consent. We investigated the promotor hypomethylation status of CAGE by methylation-specific polymerase chain reaction (MSP) using primers specific for unmethylated sequences, and found hypomethylation of CAGE promotor at a frequency approaching 90% in cervical squamous cell carcinomas (35/40, 87.5%), but at less than 4% in controls (P < 0.001). This finding provides experimental evidence of the frequent hypomethylation of normally methylated CAGE promotor CpG islands in cervical cancer, and indicates that this hypomethylation is likely to be a valuable surrogate marker for the expression of CAGE. It also provides a clue concerning the molecular mechanisms of carcinogenesis in cervical squamous cell carcinoma.

Enhanced expression of hedgehog signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions

Enhanced expression of hedgehog signaling molecules in squamous cell carcinoma of uterine cervix and its precursor lesions

Study on consecutive light microscopic changes of tumor cells and apoptotic index observed in serial cervical biopsies during neoadjuvant chemotherapy with 5-fluorouracil and cisplatin in locally advanced cervical cancer

Objective：To determine the effects of neoadjuvant chemotherapy (5-fluorouracil plus cisplatin) on tumor cell morphology and apoptosis by analyzing the consecutive changes of apoptotic index (AI) and histology observed in the serially obtained cervical cancer tissues during the chemotherapy. Methods：Cervical cancer tissues were obtained by punch biopsy just before starting the each cycle of neoadjuvant chemotherapy from five patients with locally advanced disease (stage IIb-IIIb), but previously untreated squamous cell carcinoma of uterine cervix. All patients were treated with three cycles of 5-fluorouracil (1,000 mg/ at day #1-5) and cisplatin (60 mg/ at day #1) at 3 weeks interval. All H & E stained cervical cancer tissue slides were scored for apoptotic index and observed for microscopic changes of tumor cells by a pathologist. Results：After the first cycle of chemotherapy, AI was significantly increased (from 2 times to 8 times). And widespread injury to cytoplasm was observed and followed by karyorrhexis and karyolysis of nucleus of tumor cells. The size of tumor nests was reduced and it was also noted that fibrosis and infiltration of inflammatory cells were increased. The parts of tumor nests were replaced by mature squamous cells and the changes in nuclear morphologic features pointing in a more differentiated direction. But after the second cycle of chemotherapy, only one patient showed an increase in AI by 1.2 times over that after the first cycle of chemotherapy. The rest showed slight decreases in AI compared to that after the first cycle of chemotherapy. In addition, fewer microscopic morphologic changes of tumor cells induced by chemotherapy were observed after the second cycle of chemotherapy compared to those after the first cycle of chemotherapy. Conclusion：We found that AI hardly increased or rather decreased, and that microscopic changes of tumor cells were fewer after the second cycle of neoadjuvant chemotherapy compared to the situation after the first cycle of chemotherapy. Thus, we could deduce that chemoresistance might rapidly develop in cervical cancer cells after the first cycle of neoadjuvant chemotherapy using 5-fluorouracil and cisplatin. So we need to consider this problem when we treat the locally advanced cervical cancer patients with neoadjuvant chemotherapy using 5-fluorouracil and cisplatin.

Comparison of prognosis of FIGO stage IB 1 adenocarcinoma and squamous cell carcinoma who were treated primarily by surgery

Objective：The objective of this study was to compare clinical and pathologic variables and prognosis of FIGO stage IB 1 adenocarcinoma and squamous cell carcinoma of uterine cervix who were treated primarily by surgery. Methods：From May 1982 to October 2000, 2,209 patients with invasive cancer of the uterine cervix were diagnosed and treated at Cheil Hospital. A retrospective review was performed of 533 patients with stage IB1 squamous cell carcinoma (group A) and 84 with adenocarcinoma (group B) of cervix who treated primarily by type 3 hysterectomy and pelvic and paraaortic lymphadenectomy. Results：Age, endometrial extension, lymph node metastasis and postoperative adjuvant therapy were not different between two group. There were more the lymphovascular space invasion in group A (136 patients, 25.5%) than group B (9 patients, 10.7%) (p＜0.0046). 5 year survival were 95.0% vs 93.8% for group A and group B (p=0.75). Using univariate analysis, pelvic node metastasis, paraaortic metastasis, postoperative adjuvant therapy were significant for survival. Multivariate analysis of 5 year survival revealed independent prognostic factor as postoperative adjuvant therapy. Conclusion：Prognosis of FIGO stage IB1 cervical cancer patients who were treated by primarily by type 3 hysterectomy and pelvic and paraaortic lymphadenectomy between adenocarcinoma and squamous cell carcinoma was found to be same.

Evidence of human papillomavirus infection, enhanced phosphorylation of retinoblastoma protein, and decreased apoptosis in sarcomatoid squamous cell carcinoma of uterine cervix

Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix, characterized by biphasic components of sarcomatoid and squamous neoplastic cells, is a rare entity with uncertain pathogenesis. To date, less than 20 cases have been mentioned. Although the rarity of this diagnosis makes it difficult to draw firm conclusions from limited data, it does seem that SSCC is an aggressive tumor. In this study, we present a 31-year-old patient with abnormal vaginal bleeding. The diagnosis of SSCC was confirmed through pathologic examinations from hysterectomy specimen. Its epithelial origin was demonstrated by immunohistochemical studies. The expression of p53, HER2/neu, and c-kit was not enhanced in this tumor. Importantly, it was human papillomavirus type 16, positive by polymerase chain reaction and in situ hybridization studies. Enhanced immunostaining for phospho-retinoblastoma protein and decreased apoptosis compared with the squamous cell carcinoma counterpart were observed. This report characterizes the first description of molecular features in SSCC that may account for its aggressive behavior.

Evidence of human papillomavirus infection, enhanced phosphorylation of retinoblastoma protein, and decreased apoptosis in sarcomatoid squamous cell carcinoma of uterine cervix

Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix, characterized by biphasic components of sarcomatoid and squamous neoplastic cells, is a rare entity with uncertain pathogenesis. To date, less than 20 cases have been mentioned. Although the rarity of this diagnosis makes it difficult to draw firm conclusions from limited data, it does seem that SSCC is an aggressive tumor. In this study, we present a 31-year-old patient with abnormal vaginal bleeding. The diagnosis of SSCC was confirmed through pathologic examinations from hysterectomy specimen. Its epithelial origin was demonstrated by immunohistochemical studies. The expression of p53, HER2/neu, and c-kit was not enhanced in this tumor. Importantly, it was human papillomavirus type 16, positive by polymerase chain reaction andin situhybridization studies. Enhanced immunostaining for phospho-retinoblastoma protein and decreased apoptosis compared with the squamous cell carcinoma counterpart were observed. This report characterizes the first description of molecular features in SSCC that may account for its aggressive behavior.

Relationship among HPV16 infection and Expression of hTERT, p21waf1, Ki67 in cervical intraepithelial neoplasias and squamous cell carcinomas of cervix uteri

To investigate the relationship among human papillomavirus (HPV)16 infection and the expression of telomerase catalytic protein subunit (hTERT), tumor suppressor gene p21waf1, proliferation antigen Ki67 in cervical intraepithelial neoplasias (CIN) and squamous cell carcinomas (SCC) of cervix uteri and their significance. Tissue microarray combined with in situ hybridization (ISH) and immunohistochemical staining (EliVision plus method) was used to detect the expression of HPV16 RNA, hTERT, Ki67 and p21waf1 proteins in the cervix uteri specimens from 130 subjects, including normal cervical tissue (n=26), CIN (n=46) and SCC (n=58). (1) The positive rate of HPV16 hybridization signals and expression of hTERT, Ki67 in CINII-III, in situ carcinoma and invasive SCC were all significantly higher than in normal cervical tissue (P < 0.05 for all), and was also higher in SCC than in CIN (P < 0.05 for all). There was a significant difference among CIN I, II and III (P < 0.05 for all). (2) The positive expression of p21waf1 protein only in SCC was significantly lower than in normal cervical tissue (P < 0.05), but there was no significant differences among other groups (all P > 0.05). (3) The positive rate of HPV16 and the expression of Ki67 showed respectively positive being correlated with the expression of hTERT (P < 0.05, r=0.339; P < 0.05, r=0.398); HPV16, hTERT and Ki67 showed respectively negative correlation with the expression of p21waf1 (P < 0.05, r=-0.337; P < 0.05, r=-0.248; P < 0.05, r=-0.446); There was no significant relation between HPV16 and Ki67 (P > 0.05). The results suggest that in tissues of CIN and SCC changes in hTERT, p21waf1 and Ki67 expression may be associated with HPV16 infection and they interact with each other, which can influent the progression of CIN and carcinogenesis of SCC. These biomarkers may be analyzed comprehensively to reveal the detailed mechanism by which HPV16 participate in malignant transformation and to provide some informations on the diagnosis of patients with high risk for malignant progression. Tissue microarray is an efficient platform for high-throughput analysis of genes and their expression products in investigations.

Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy

Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy

Cyclin D1 G870A polymorphism and squamous cell carcinoma of the uterine cervix in Korean women

Cyclin D1 G870A polymorphism and squamous cell carcinoma of the uterine cervix in Korean women

293 Comparison of Dna Hypermethylation Profiles of 15 Tumor-Suppressor Genes Between Adenocarcinoma and Squamous Cell Carcinoma of Uterine Cervix

293 Comparison of Dna Hypermethylation Profiles of 15 Tumor-Suppressor Genes Between Adenocarcinoma and Squamous Cell Carcinoma of Uterine Cervix

741 Direct Connection Ofadenoid Basal Cell Carcinoma of Uterine Cervix to Cervical Intraepithelial Neoplasia

741 Direct Connection Ofadenoid Basal Cell Carcinoma of Uterine Cervix to Cervical Intraepithelial Neoplasia

294 Hypermethylation of Mage Gene Family and Cage1 Promotors in Squamous Cell Carcinoma of Uterine Cervix

294 Hypermethylation of Mage Gene Family and Cage1 Promotors in Squamous Cell Carcinoma of Uterine Cervix

Phase I/II study of alternating chemoradiotherapy using 5fu and nedaplatin for patients with high-risk group of cervical carcinoma; a comparison to the historical control group using pre-treatment MRI evaluation

Phase I/II study of alternating chemoradiotherapy using 5fu and nedaplatin for patients with high-risk group of cervical carcinoma; a comparison to the historical control group using pre-treatment MRI evaluation

Conventional and array-based comparative genomic hybridization analyses of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine cervix

We established 2 novel human cell lines (GCCOT-1, GCCRK) from glassy cell carcinoma. Both cell lines showed dual tendencies of glandular and squamous differentiation, and thus possess the characteristics resembling reserve cells, the putative origin of most carcinomas arising from the uterine cervix. HPV type 18 DNA including E6-E7, which is commonly found in cell types other than squamous cell carcinoma of uterine cervix, was detected in both cell lines. We analyzed gene copy number alterations of the 2 cell lines using conventional comparative genomic hybridization (CGH) coupled with array-based CGH. Among the putative oncogenes demonstrating copy number gain in both cell lines, FGR(SRC2) at 1p36.2-1 and LAMC2 at 1q25-31 have not been reported to show amplification in previous analyses of conventional cervical cell lines. These oncogenes are thus speculated to be directly associated with oncogenesis of glassy cell carcinoma. On the other hand, among the putative suppressor genes demonstrating copy number loss in both cell lines, the 9q region, ATM at 11q22.3, and CYLD at 16q12-13 have not been reported to show loss in conventional cervical cancer cell lines. These sites are speculated to be important as tumor suppressors directly associated with oncogenesis of glassy cell carcinoma. This study suggests for the first time that together with the presence of HPV type 18, alterations at the above sites are closely associated with oncogenesis of glassy cell carcinoma, a special type of carcinoma in the uterine cervix.

Differential Gene Expression in Uterine Cervical Cancer

Objective : Identification of the genes differentially expressed in cervical cancer but not in the non-cancerous cervix is important for understanding the molecular basis of cervical cancer and for defining possible prognostic value and therapeutic intervention. We investigated the changes in gene expression accompanying the development and progression of cervical cancer by cDNA microarray. Methods : To identify molecular alterations in squamous cell carcinoma of uterine cervix, we measured expression profiles for paired cancer and noncancerous cervix samples from three individuals by means of a cDNA microarry representing 17,000 genes. Results : The 36 genes were noted to have more than a three-fold change in expression (either increased or decreased) in cervical squamous cell carcinoma compared to the non-cancerous cervix in all three experiments. The changed genes are those associated with cell proliferation/apoptosis, signal transduction/transcription, extracellular matrix, enzyme, immune response, cytoskeleton, angiogenesis and others. Conclusion : The authors predicted that these gene expression profiling experiments will lead to improvements in the basic understanding of pathogenesis of cervical cancer and will promote the discovery of novel molecular markers for cervical cancer diagnosis and therapy.

A new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity in children.

The evaluation of estrogenic status is necessary for many physiological and pathological conditions in pediatric as well as adult endocrinology. Because current immunoassays exclusively measure E2--and with a sensitivity that is insufficient for prepubertal children--we developed a new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity. This assay is based on human uterine cervix carcinoma cells, HeLa cells, that do not naturally express E2 receptor. These cells were transfected with plasmids encoding the human ERalpha or beta, along with an estrogen-responsive promoter fused to the luciferase gene, and called HELNalpha and HELNbeta for HeLa estrogen-responsive element luciferase neomycin alpha and beta. HELNalpha and HELNbeta are able to respond to estrogens and various compounds having estrogenic activity but, because of the importance of ERalpha in the reproductive function, we chose to work with the HELNalpha cell line. The luciferase activity we obtained was compared with an E2 standard curve specific for each serum sample and established with stripped serum. The estrogenic bioactivity was expressed in picograms of E2 equivalents, and the detection limit was < 1 pg x ml(-1) E2 equivalents. The intra and interassay error was lower than 10% and 20%, respectively. We measured estrogenic bioactivity in 18 normal prepubertal boys (age = 9.7 +/- 2.4 yr), 18 normal prepubertal girls (age = 9.2 +/- 1.7 yr) and 18 normal pubertal girls (age = 13.6 +/- 1.8 yr). The estrogenic bioactivity in the prepubertal girls was significantly higher than in the boys, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 1.44 +/- 0.87 pg x ml(-1) (P < 0.01). A significant difference was found between the pre- and pubertal girls, i.e. 3.53 +/- 2.23 pg x ml(-1) vs. 26.77 +/- 18.32 pg x ml(-1) (P < 0.01). This ultrasensitive bioassay measures total estrogenic bioactivity of serum with very high sensitivity. It has numerous potential applications in pediatric and adult endocrinology. In addition, this assay may help to evaluate excess estrogenic activity related to aromatase overexpression or contamination by environmental chemicals.

Hepatic pseudocyst as the first presentation of squamous cell carcinoma of uterine cervix

Hepatic pseudocyst as the first presentation of squamous cell carcinoma of uterine cervix