Comparison of digene hybrid capture 2, GeneMatrix PapilloScreen, and a PCR sequencing assay in detecting high-risk and probable high-risk oncogenic HPV genotypes in specimens from Korean women.

Most cervical cancers are caused by 15 high-risk (HR) and three probable high-risk (pHR) oncogenic types of human papillomavirus (HPV). However, current commercial HR HPV screening test products do not include pHR HPV genotypes. Recently, PapilloScreen has been developed to detect the 15 HR and three pHR HPV types. In this study, we evaluated the concordance levels and clinical performance of Hybrid Capture 2 (HC2), PapilloScreen, and a PCR sequencing assay in detecting HR and pHR HPV. The PapilloScreen (96.8 %) and PCR sequencing assay (96.8 %) demonstrated higher sensitivity than HC2 (80.7 %) for detecting HR and pHR HPV. The three assays showed similar specificities and positive or negative predictive values. The concordance levels were 86.5 % (κ = 0.68) and 86.5 % (κ = 0.67) between HC2 and PapilloScreen and between HC2 and PCR sequencing, respectively. A near-perfect concordance was observed between PapilloScreen and PCR sequencing (97.8 %, κ = 0.95). Overall, the agreement between the three assays suggests that the results obtained by the HC2 assay are more often discordant (12.6 %) than the PCR-based tests. In conclusion, PapilloScreen is highly sensitive for detecting high-grade CIN or cervical cancer. The PapilloScreen assay should be considered an accurate and sensitive method for detecting HR and pHR HPV infections and an epidemiological tool for prevalence studies as well as early diagnosis and intervention in HR and pHR HPV infections.

Comparison of the clinical performance of restriction fragment mass polymorphism (RFMP) and Roche linear array HPV test assays for HPV detection and genotyping.

BACKGROUND: The need for accurate genotyping of human papillomavirus (HPV) infections is becoming increasingly important as HPV is the primary cause of cervical cancer worldwide. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based restriction fragment mass polymorphism (RFMP) assay provides accurate, broad-spectrum, high-throughput genotyping of HPV. OBJECTIVES: We evaluated the clinical performance of the RFMP assay compared to a commercially available Roche linear array HPV genotyping test (LA) for detecting and genotyping of HPV. STUDY DESIGN: The RFMP assay and the LA were compared for detecting and genotyping HPV among a cohort of 244 liquid-based cytology samples. RESULTS: Overall, 216 specimens (93.1%, κ = 0.86) generated concordant results for the presence or absence of high-risk HPV (HR-HPV) by the two assays. The RFMP assay and the LA assay generated concordant, compatible, and discordant genotyping results for 79.3, 9.9, and 10.8%, respectively. The diagnostic sensitivity and specificity of RFMP and LA for the cervical lesions of squamous cell carcinoma (SCC) were similar, at 92.9 and 85.0% (RFMP) and 92.9 and 83.8% (LA), respectively. In addition, the odds ratio for SCC with HR-HPV positivity estimated by the RFMP assay (73.7, 95% CI: 8.9-3173.3) was higher than the LA assay (67.0, 95% CI: 8.2-2887.0). CONCLUSIONS: The RFMP and the LA assays were highly comparable with regard to detection and genotyping analysis of HPV. The sensitivity and specificity of RFMP assay for the detection of HR-HPV in various levels of cervical lesions seems to be valuable in the monitoring of HPV-associated cervical cancer.

Analytical and clinical performances of a restriction fragment mass polymorphism assay for detection and genotyping of a wide spectrum of human papillomaviruses.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry-based restriction fragment mass polymorphism (RFMP) assay was adapted to human papillomavirus (HPV) genotyping. The analytical sensitivity and the clinical utility were evaluated by testing defined HPV genome equivalents and a total of 426 specimens composed of normal cytology, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion and invasive squamous cell carcinoma. The RFMP assay was able to detect 38.4-114.6 genomic equivalents of a wide variety of HPV types. The RFMP assay detected 34 different HPV genotypes in cervical samples of which 8% were found to be multiple-type infections. The high-risk HPV positivity rate according to the histological diagnosis was 7.9% (8/101), 31.7% (38/120), 50% (55/110), 86% (37/43), 96.2% (50/52) in normal, atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion and squamous cell carcinoma subgroups, respectively. Diagnostic sensitivities/specificities for the cervical lesions of squamous cell carcinoma and high grade squamous intraepithelial lesion or worse histology were found to be 96.2%/92.1% and 91.6%/92.1%, respectively. The sensitivity, accuracy, wide range of genotype identification and high-throughput capacity with cost-effectiveness of the test consumables make the RFMP assay suitable for mass screening and monitoring of HPV-associated cervical cancer.

Comparison of the efficacy between paclitaxel/carboplatin and doxorubicin/cisplatin for concurrent chemoradiation in intermediate- or high-risk endometrioid endometrial cancer: a single institution experience.

AIM: We sought to compare survival and toxicity between paclitaxel/carboplatin (TC) and doxorubicin/cisplatin (AP) for concurrent chemoradiation (CCR) in intermediate- or high-risk endometrioid endometrial cancer. METHODS: The clinical data of 40 patients with intermediate- (FIGO stage IC-IIB, n = 12) or high-risk endometrioid endometrial cancer (FIGO stage IIIA-IVA, n = 28) were reviewed retrospectively between March 2000 and December 2007, who were treated with TC (n = 23, group 1) or AP (n = 17, group 2) for CCR after surgery. RESULTS: Progression-free survival (PFS) and overall survival (OS) were not different between groups 1 and 2 (median PFS and OS; 35 vs 24 and 76 vs 39 months, respectively, P > 0.05). However, >or=6 cycles of chemotherapy improved PFS compared with 3-5 cycles of chemotherapy (51 vs 21 months, P = 0.04), suggesting that >or=6 cycles of chemotherapy was an independent prognostic factor improving PFS (adjusted HR, 0.27; 95% CI, 0.08 to 0.91; P = 0.04). Grade 3 or 4 hematological and non-hematological, especially, gastrointestinal, toxicities related with chemotherapy during CCR were more common in group 2 than in group 1, whereas there was no difference in grade 3 or 4 late complication by CCR between the 2 groups. CONCLUSION: These findings suggest that TC may have comparable efficacy to AP for CCR with lesser toxicity, and >or=6 cycles of chemotherapy may be more beneficial than 3-5 cycles of chemotherapy in intermediate- or high-risk endometrioid endometrial cancer. However, large-scale randomized controlled trials are needed to support these results.

Postoperative nomogram predicting risk of recurrence after radical hysterectomy for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to develop a nomogram for predicting the 5-year disease-free survival (DFS) after radical hysterectomy for early-stage cervical cancer. PATIENTS AND METHODS: An institutional database of 275 consecutive patients treated at Seoul National University Hospital for stage I to stage IIA cervical cancer was used to develop a nomogram based on Cox proportional hazards regression model. The developed nomogram was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve. External validation was also performed using an independent data set of patients from Asan Medical Center. RESULTS: From Cox regression analysis, disease stage, number of positive lymph nodes, parametrial involvement, and depth of invasion were identified as independent risk factors for disease recurrence (P < 0.05). The nomogram incorporating these factors appeared to be accurate and predicted the outcomes better than the International Federation of Gynecology and Obstetrics stage alone (concordance index, 0.858 compared with 0.719; P = 0.001). When applied to a separate validation set, the nomogram also showed similar predictive accuracy (concordance index, 0.879). CONCLUSION: We have developed a nomogram that can predict the recurrence risk in patients with early-stage cervical cancer after surgery, which was internally and externally validated.

Cyclooxygenase-2 expression in cervical intraepithelial neoplasia.

To evaluate the role of cyclooxygenase (COX)-2 during cervical carcinogenesis, we investigated COX-2 expression in the dysplastic epithelium and stromal cells of cervical intraepithelial neoplasia (CIN). Immunohistochemical analysis with COX-2 antibody was performed on 148 paraffin-embedded tissue specimens of patients who were diagnosed as CIN in our institute. COX-2 expression was evaluated separately in the dysplastic epithelium and stromal cells of CIN. The relationships between COX-2 expression and clinicopathologic variables were examined. For the dysplastic epithelium, COX-2 expression was negative in 137 (92.6%) and positive in 11 (7.4%) specimens. For the stromal cells, COX-2 expression was negative in all specimens. The COX-2 expression in dysplastic epithelium was higher in older (P= 0.038) or postmenopausal (P= 0.025) women. In conclusion, COX-2 expression was observed only in the dysplastic epithelium but not in the stromal cells of CIN. The COX-2 expression in dysplastic epithelium was associated with age and menopausal status.

Phase I/IIa study of combination chemotherapy with CKD-602 and cisplatin in patients with recurrent epithelial ovarian cancer.

The aim of this study was to determine the maximum tolerated dose (MTD) and therapeutic efficacy of a newly developed CKD-602 topoisomerase I inhibitor and cisplatin in patients with recurrent epithelial ovarian cancer. CKD-602 (0.30 mg/m(2) daily for 5 days) and cisplatin (60 mg/m(2) on day 5) were administered to patients every 3 weeks with dose adjustment of CKD-602 by 0.05 mg/m(2) daily until the MTD was reached. Dose-limiting toxicity was defined as grade >or= 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever >or= 38.5 degrees C, infection, hemorrhage, or transfusion; grade >or= 3 nonhematological toxicity except for alopecia, nausea, and vomiting. We enrolled 26 patients with recurrent epithelial ovarian cancer who had measurable disease (MD) estimated by computed tomography scan (n= 12) and nonmeasurable disease (NMD) evaluated by serum CA-125 levels (n= 14). All patients received 188 cycles of CKD-602 and cisplatin with a median number of six cycles per patient (range, 2 to 12). MTD of CKD-602 was 0.30 mg/m(2) daily. The overall response rate was 69.2% (18/26) with 58.3% (7/12) and 78.6% (11/14) in MD and NMD, respectively. Among the responsive patients, 14 were platinum sensitive (14/18, 77.7%) and four were platinum resistant (4/8, 50.0%). The most common toxicity was grade >or= 3 neutropenia developing in 17 patients (65.4%) and 72 cycles (38.3%). Grade 3 nausea and anorexia were the most common gastrointestinal toxicities, developing in 15 cycles (8.0%) of four patients (15.4%) and 10 cycles (5.3%) of five patients (19.3%), respectively. The median disease-free interval was 6 months (range 0-26 months). CKD-602 at a concentration of 0.3 mg/m(2) daily for 5 days and cisplatin at 60 mg/m(2) on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum-sensitive/resistant recurrent epithelial ovarian cancer.

Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays.

A major obstacle in treatment of epithelial ovarian cancer is chemoresistance. The aim of this study was to determine whether distinct gene expression profiles are associated with chemoresistance in epithelial ovarian carcinoma. We performed global gene expression analysis in 13 primary epithelial ovarian cancer tissues including 5 primary chemosensitive tumors and 8 primary chemoresistant tumors using Affymetrix HGU133A microarray. The gene expression patterns of chemosensitive tumors were compared with those of chemoresistant tumors using fold change. Validity of microarray results was examined by semiquantitative RT-PCR. We identified over 320 genes differentially expressed in chemoresistant epithelial ovarian cancer (> or = twofold). Upregulated genes in chemoresistant tumors included cell cycle regulating genes (TOP2A, BCAT1, CDCA8, CCNA2, CENPE), and genes with previously known mechanisms in tumorigenesis (S100A9, APOA1, RNF125, IFI16). Downregulated genes in chemoresistant tumors included genes related to cell adhesion (MUC5B, CITED2), transcription regulating genes (FOXD1, MAD1L1, PAX2), genes involving signal transduction (SOSTDC1, SNX1, SFRP1, FOXA2, PLK2), and stress protein gene (TP53AP1). These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. This type of molecular profiling could provide a basis for additional functional studies.

Phase II evaluation of CKD-602, a camptothecin analog, administered on a 5-day schedule to patients with platinum-sensitive or -resistant ovarian cancer.

BACKGROUND: To evaluate the toxicity and efficacy of a newly developed topoisomerase I inhibitor, CKD-602 in second-line therapy of ovarian cancer. METHODS: We enrolled 24 patients with recurrent ovarian cancer, of median age 54 years (range, 39-64). Eleven patients had measurable lesions on CT scan, and the other 13 had increased serum CA-125 levels. Eighteen patients had platinum-sensitive disease (minimum treatment free interval > or =6 months) and 6 had platinum-resistant disease (minimum treatment free interval <6 months). CKD-602 (0.5 mg/m(2)/day) was administered intravenously for 5 days every 3 weeks. The median number of courses per patient was 6 (range, 1 to 12). Response was evaluated by the evaluation of the size of the mass by CT scan and CA-125 response. RESULTS: The overall response rate was 45.0% (9/20), with 4 patients exhibiting partial responses and 5 patients exhibiting 75% CA-125 responses in 20 evaluable patients. Of the 9 responsive patients, 8 were platinum-sensitive (8/15, 53.3%) and 1 was platinum-resistant (1/5, 20.0%). An additional 5 patients showed stable disease, whereas 6 patients exhibited progressive lesions. Of 24 patients, the most common toxicity was hematological, with grades 3 or 4 neutropenia developing in all 24 patients (100%) and in 94 cycles (71.7%). Grade 3 thrombocytopenia developed in 4 patients (16.7%) and 6 cycles (4.6%). None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia. CONCLUSIONS: The newly developed topoisomerase I inhibitor, CKD-602, showed activity against both platinum-sensitive and -resistant ovarian cancer, with acceptable toxicity.

Feasibility of routine lymphadenectomy in clinical stage-I endometrial cancer.

BACKGROUND: To determine the accuracy of several preoperative tests in predicting lymph node (LN) metastases and the feasibility of doing a routine lymphadenectomy in clinical stage-I endometrial cancer. MATERIAL/METHODS: We reviewed 132 patients with clinical stage-I endometrial cancer. The preoperative tests used to predict LN metastases were serum CA-125 level, histologic type and grade, LN status assessed by pelvic magnetic resonance image (MRI) or computed tomography (CT), and depth of myometrial invasion assessed only by pelvic MRI. The cutoff value of the serum CA-125 level was determined using receiver operating characteristic curves. Multivariate logistic regression analyses were used to determine which tests are good predictors of LN metastases. RESULTS: Of 132 patients, 13 (9.8%) had LN metastases. On univariate logistic regression analysis, a high CA-125 level and preoperative LN evaluation by pelvic MRI or CT were significant predictors for LN metastases (OR=17.41, 95% CI: 4.36-69.56 and OR=14.30, 95% CI: 4.02-50.63, respectively). However, on multivariate logistic regression analysis adjusted for age and all preoperative tests, a high CA-125 level was the most significant predictor (OR=13.73, 95% CI: 2.03-92.73). Among the 97 patients with no significant predictor of LN metastases, pelvic LN metastases were observed in 3 patients (3.1%) and para-aortic LN metastases were observed in 1 patient (1.1%). Surgical complications were mild (lymphocele, n=9; lymphedema, n=2; wound problem, n=2). CONCLUSIONS: Considering the importance of LN metastases as an indicator of prognosis, and the relatively low surgical risk of lymphadenectomy, clinicians should cautiously consider routine lymphadenectomy in patients with clinical stage-I endometrial cancer.

Predictive value of individualized tumor response testing by ATP-based chemotherapy response assay in ovarian cancer.

The aim of this study is to investigate the correlation between ATP-based chemotherapy response assay (ATP-CRA) results and clinical outcomes in ovarian cancer. Twenty-nine fresh tumor specimens were collected. Tumor cells were isolated and cultured for 48 hrs in medium containing anticancer drugs. The median age of patients was 56 years. The sensitivity, positive predictive value, and accuracy of ATP-CRA were respectively 94.1%, 94.1%, and 90.0%. There was a significant relationship between ATP-CRA results and clinical responses (p = 0.046). This study suggests that ATP-CRA has high sensitivity, positive predictive value, and accuracy for predicting response to chemotherapy in ovarian cancer.

Interleukin-12 p40 gene (IL12B) polymorphisms and the risk of cervical cancer in Korean women.

OBJECTIVE: The aim of this study was to investigate whether IL12B polymorphisms might be associated with increased risk and invasiveness of cervical cancer in Korean women. STUDY DESIGN: Peripheral blood samples from patients with invasive cervical cancer (n=154) and non-cancer controls (n=191) were used to detect three biallelic IL12B polymorphisms at IVS2 -912, IVS4 +314, 3'UTR +1188 sites by performing SNaPshot assay. Allelic frequencies, genotype distributions, and haplotype patterns in the case group were compared with those in the control group. The relationships between these polymorphisms and cancer invasiveness were also evaluated by collating the clinicopathologic parameters including FIGO stage, lymph node status, histologic type, and parametrial invasion. The used analytic methods are chi-square test and logistic regression analysis. RESULTS: Allelic frequencies of cases (G, 0.853; A, 0.147) were not significantly different from controls (G, 0.796; A, 0.204) in IVS2 -912G/A SNP (P=0.054). GG genotype of IVS2 -912G/A SNP showed increased risk for cervical cancer compared with AA genotype (P=0.040). The IVS2 -912G:IVS4+314A haplotype, IVS2 -912G:IVS4 +314A:3'UTR +1188A haplotype, and IVS2 -912G:IVS4 +314A:3'UTR +1188C haplotype were also significantly associated with increased risk for cervical cancer. A subgroup analysis of the clinicopathologic parameters in cancer group also showed that there is no significant association between IL12B polymorphisms and cervical cancer invasiveness. CONCLUSIONS: This study suggests that IVS2 -912GG genotype and IVS2 -912G:IVS4 +314A haplotype of IL12B gene are associated with increased risk for cervical cancer in Korean women.

Gamma-knife radiosurgery as an optimal treatment modality for brain metastases from epithelial ovarian cancer.

OBJECTIVES: The objectives of this study are to analyze the clinical feature and overall survival rate of patients with brain metastases from epithelial ovarian cancer (EOC) and to compare the treatment outcomes of gamma-knife radiosurgery (GKS) and whole-brain radiation therapy (WBRT). METHODS: A retrospective chart review of patients diagnosed with brain metastases from EOC in a single institution between 1983 and 2005 was performed. Of 1413 patients with EOC, 18 (1.3%) developed brain metastases. Fifteen patients who were treated with GKS or WBRT were enrolled for this study. Seven patients were treated with GKS, and the remaining patients were treated with WBRT as a primary treatment modality. RESULTS: The median age at the time of diagnosis of the primary cancer and brain metastases was 55 and 56 years, respectively. The median interval between the diagnosis of the primary cancer and brain metastases was 28 months. It was significantly associated with the overall survival rate after the diagnosis of ovarian cancer (p=0.017). There were 5 patients (33.3%) with extracranial metastases. Five patients (33.3%) had a solitary brain lesion. The median survival time after the diagnosis of brain metastases was 14 months (range, 1-59 months). Patients who were treated with GKS after brain metastasis had a longer survival time (median, 29 months) than those treated with WBRT (median, 6 months) (p=0.0061). CONCLUSION: For the control of brain metastases, GKS seems to be an effective modality. GKS improves the overall survival of the patients with brain metastases from EOC.

Hereditary nonpolyposis colorectal cancer in endometrial cancer patients.

Endometrial cancer is the second most common cancer in hereditary nonpolyposis colorectal cancer (HNPCC). It has often been overlooked to explore the possibility of HNPCC in endometrial cancer patients. Our study was to investigate how many HNPCC patients existed among endometrial cancer patients. Among patients who underwent hysterectomy for endometrial cancer at Seoul National University Hospital from 1996 to 2004, 113 patients were included, whose family history and clinical data could be obtained and tumor specimens were available for microsatellite instability (MSI) testing and immunohistochemical (IHC) staining of MLH1, MSH2 and MSH6 proteins. There were 4 (3.5%) clinical HNPCC patients fulfilling the Amsterdam criteria II, and 2 (2/4, 50%) of them carried MSH2 germline mutations. There were also 8 (7.1%) suspected HNPCC (s-HNPCC) patients fulfilling the revised criteria for s-HNPCC, and one (1/8, 12.5%) of them revealed MLH1 germline mutation. In 101 patients, who were not clinical HNPCC or s-HNPCC, 11 patients showed both MSI-high and loss of expression of MLH1, MSH2 or MSH6 proteins, and 2 (2/11, 18.2%) of them showed MSH6 germline mutations. In 113 patients with endometrial cancer, we could find 5 (4.4%) HNPCC patients with MMR germline mutation and 2 (1.8%) clinical HNPCC patients without identified MMR gene mutation. Family history was critical in detecting 3 HNPCC patients with MMR germline mutation, and MSI testing with IHC staining for MLH1, MSH2 and MSH6 proteins was needed in the diagnosis of 2 HNPCC patients who were not clinical HNPCC or s-HNPCC, especially for MSH6 germline mutation.

Trends in cervical cancer mortality in Korea 1993-2002: corrected mortality using national death certification data and national cancer incidence data.

Cervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993-2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered "uterus, unspecified" deaths previously registered as "cervix, uterine" cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age-specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age-standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): -4.05%, 95% CI: -4.88, -3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30-69 years, it increased substantially in women aged > or =70 years (EAPC: 3.62%, 95% CI: 1.92-5.35). Results of this study will provide evidence-based foundation for the evaluation of the existing cervical cancer-screening programs.

Efficacy and outcome of anterior vaginal wall repair using polypropylene mesh (Gynemesh).

AIM: The aim of the present study was to assess the safety and efficacy of anterior vaginal wall repair using polypropylene mesh for the correction of anterior vaginal wall prolapse. METHODS: From May 2001 to March 2005, 38 patients with cystoceles or uterine prolapse underwent transvaginal repair with implantation of polypropylene mesh. In all 38 patients anterior vaginal wall repair was done concurrently with other procedures: vaginal hysterectomy, n = 18 (47.4%) and tension-free vaginal tapes n = 22 (57.9%). RESULTS: Preoperatively 26 patients (68.4%) had stage III/IV prolapse on pelvic organ prolapse quantification examination. After mean follow up of 23.4 months, the objective cure rate at 12 and 18 months was 94.5% and 94.3%, respectively. As for complications associated with placement of the polypropylene mesh, no tissue erosion or infection was found. CONCLUSIONS: Transvaginal implantation of polypropylene mesh is an effective and safe technique for the correction of anterior vaginal wall prolapse.

Increasing trend in the incidence of cervical cancer among the elderly in Korea: a population-based study from 1993 to 2002.

Cancer is primarily a disease of older adults. However, little data is available on the clinical features of cervical cancer in elderly patients. We investigated the trends in incidence and clinical features associated with cervical cancer among the elderly in Korea during the period of 1993-2002. We obtained data from the National Cervical Cancer Incidence Database, which was constructed in collaboration with the Korea Central Cancer Registry (KCCR) and Korea Gynecologic Cancer Registry (KGCR). A total of 44 191 women with cervical cancer were diagnosed between 1993 and 2002. Patients were divided into three groups based on age: /=70 years (Group 3). During this period, upward incidence trends were noted in Group 3 while constant and downward incidence trends were noted in Groups 1 and 2, respectively. Pooled analysis across years revealed that squamous cell carcinoma and advanced stage (IIB, III, and IV) were more common in Group 3 than in Groups 1 and 2. With regard to primary treatments in the elderly patients, surgery appeared to be performed increasingly despite the fact that advanced stage (IIB, III, and IV) was more common in Group 3 than in Groups 1 and 2. Our findings suggest that the incidence of cervical cancer in the elderly is increasing in Korea, while it is decreasing overall. The current health service must emphasize education for the elderly about cervical cancer prevention while concentrating on screening.

Influences of cyclooxygenase-1 and -2 expression on the radiosensitivities of human cervical cancer cell lines.

We utilized three cervical cancer cell lines (HeLa, HT-3, and C33A) and clonogenic assays to determine whether cyclooxygenase (COX) expression is related to radiosensitivity. Using COX DNA transfection and COX inhibition by siRNA, we also examined changes in radiosensitivity caused by variations in COX expression. The survival fractions of HeLa and HT-3 cell lines, which both with COX-1 and COX-2 activity, were found to be significantly higher than that of the C33A cell line which had neither COX-1 nor COX-2 activity. Moreover, the acquisition of COX-1 in C33A cell line significantly reduced its radiosensitivity, but COX-2 transfection increased radiosensitivity in this cell line. In addition, the inhibition of COX-1 activity in HT-3 cell line using siRNA resulted in an increased radiosensitivity, but this phenomenon was not observed for COX-2 inhibition. The same experiment in HeLa cells using siRNA also showed no significant change in radiosensitivity. The results obtained during this study suggest that COX expression is associated with the radiosensitivity in uterine cervical cancer cell lines and COX-1 might have more important role than COX-2.

Can preoperative MRI accurately evaluate nodal and parametrial invasion in early stage cervical cancer?

OBJECTIVE: To evaluate the diagnostic performance of magnetic resonance imaging (MRI) in the pretreatment evaluation of invasive cervical cancer especially for the parametrial invasion and lymph node (LN) involvement. METHODS: We retrospectively recruited consecutive patients with biopsy-confirmed cervical cancer who had undergone preoperative MRI and were scheduled for surgery based on clinical assessment between January 2004 and May 2006. We evaluated the diagnostic performance of MRI for the parametrial invasion and LN involvement using surgicopathologic findings as the reference standard. RESULTS: A total of 119 eligible patients completed preoperative and intra-operative survey, of whom 34 (28.6%) had pelvic LN metastasis and four (3.4%) had para-aortic LN metastasis histologically. The sensitivity, specificity and accuracy of MRI in detecting LN involvement by region-specific analysis were 40.5, 91.3 and 86.8% respectively. The sensitivity, specificity and accuracy of MRI in detecting parametrial invasion were 44.4, 89.1 and 88.3% respectively. The positive predictive value (PPV) of preoperative MRI for detecting region-specific LN involvement and parametrial invasion was 31.3 and 61.2%, respectively. Imaging findings of suspected parametrial invasion were not to influence the treatment decision in the study. CONCLUSION: Preoperative MRI showed low PPV for detecting LN involvement and parametrial invasion in cervical cancer. Further studies are necessary to determine the cost-effectiveness of using MRI in place of conventional clinical staging tests according to clinical indication and also its use in comparison with that of integrated positron emission tomography/computed tomography.

Matrix metalloproteinase-1 promoter polymorphism and epithelial ovarian cancer: does ethnicity matter?

AIM: To estimate the relationship between matrix metalloproteinase (MMP)-1 promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in Korean women and to clarify the ethnic difference in genotype distribution of this polymorphism. METHODS: Single nucleotide polymorphism (SNP) of MMP-1 promoter -1607 region in 133 EOC patients and 332 cancer-free patients were investigated. Then the associations of this polymorphism with EOC or its clinicopathological parameters were analyzed. In addition, genotype distributions of this polymorphism in Korean women were compared with those of other races by extracting data from the previously published literature. RESULTS: We found no relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian cancer in a Korean population. Furthermore, we found ethnicity-dependent differences in genotype distributions and allele frequencies by comparison with previous articles on this topic. We report significant ethnic differences in the genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp polymorphism. CONCLUSION: Our results indicate that MMP-1-1607 bp polymorphism shows ethnic diversity, and that the hypothesis that this polymorphism is associated with epithelial ovarian cancer is not supported by this study in a Korean population. Moreover, this finding concurs with results obtained in white Americans and Europeans.