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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Aromatase expression was not detected by immunohistochemistry in endometrial cancer.

Several studies suggested that aromatase could play an important role in tumor progression and prognosis in endometrial cancer because androstenedione is converted to estrogen by the enzyme. For better understanding of the aromatase expression in endometrial cancer and its relation to diverse clinicopathological parameters, we conducted this study. This study was carried out with 141 endometrial cancer patients, all of whom had undergone operations in our institution from 1993 to 2002. Paraffin-embedded tissue blocks were sectioned and immunostained with monoclonal antiaromatase antibody using human placental tissue as positive control. Clinicopathological variables of all patients were also reviewed. Despite quite a high aromatase expression in positive control, there was no endometrial cancer specimen showing the enzyme expression. Our result, although needs further investigation on the cause of the difference from other studies, suggested that aromatase might not have an important role in endometrial cancer.

Lack of association of the cyclooxygenase-2 and inducible nitric oxide synthase gene polymorphism with risk of cervical cancer in Korean population.

Currently, many studies have shown that nitric oxide (NO) and prostaglandin (PG) are main inflammatory mediators involved in a variety of pathophysiological processes including inflammation and carcinogenesis. In this article, we explored the possible association of polymorphisms, of two representative inflammatory mediators, with the risk for cervical cancer. This study included 176 cases of histologically confirmed invasive cervical cancer, and 172 healthy controls. Allele frequency of 12 single-nucleotide polymorphisms (SNPs) of cyclooxygenase-2 (COX-2) and COX5 of the inducible nitric oxide synthase (iNOS) genes in 43 different normal populations were analyzed. We found that 14 of 17 showed a monomorphic or minimal minor allele frequency; therefore, we did not continue with additional analysis. Three SNPs (2 for COX-2, 1 for iNOS) were chosen for the study. Genotyping of three SNPs (SNP-rs5275 in the untranslated region of exon 10 and rs5277 in the coding region of exon 3 of COX-2, and iNOS Ser(608)Leu allele C/T polymorphism within exon 16 of the iNOS reductase domain) was performed. No significant increase was found in any of the genotypes of the COX-2 or iNOS in the cancer group. We investigated the possible correlation between the genotypes and the clinicopathologic parameters of cervical cancer. No significant association of the genotypes studied was found with respect to clinical stage, lymph node (LN) status, histologic type, or parametrial invasion. Our data did not reveal an association between COX-2 and iNOS polymorphisms with cervical cancer in Korean women.

Increased cyclooxygenase-2 expression associated with inflammatory cellular infiltration in elderly patients with vulvar cancer.

As the relationship between inflammation and carcinogenesis grows stronger, the role of cyclooxygenase-2 (COX-2) and epidermal growth factor (EGFR) has been highlighted in the pathogenesis and progression of human cancer. In view of the fact that vulvar cancer is characterized by precancerous inflammatory changes in elderly patients, the expressions of COX-2 and EGFR are expected to show different patterns of distribution according to age and other prognostic factors. To verify whether there was a relationship between their expression and clinicopathologic parameters in vulvar cancer, we investigated the inflammatory cellular infiltration and the expression of COX-2 and EGFR by immunohistochemical analysis. Eleven of 19 samples (57.8%) were stained positive for COX-2, and 17 (89.4%) for EGFR. The portion of inflammatory cellular infiltration in adjacent normal tissue was also higher in the older age group, and showed a strong correlation with COX-2 positivity (P = 0.002). Furthermore, COX-2 expression was significantly more frequent in patients over 60 years of age compared to those under 50 years (P = 0.009). COX-2 expression was noted to be high in moderate and well-differentiated cases, whereas, poorly differentiated carcinoma was negative for COX-2 expression (P = 0.023). However, EGFR expression was not differently distributed on the basis of stage, age, tumor grading, or presence of lymph node metastasis. Our article suggests that vulvar cancer in elderly patients may be associated with inflammation, and thus with increased COX-2 expression. In light of these findings, a clinical trial designed to assess the addition of COX-2 targeted therapy to conventional treatment in vulvar cancer would be helpful for consideration of additional treatment options and possibly avoiding the serious surgical morbidity in elderly patients.

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.

The C19007T polymorphism of ERCC1 and its correlation with the risk of epithelial ovarian and endometrial cancer in Korean women. A case control study.

BACKGROUND: Excision repair cross-complementing group 1 (ERCC1) is a major DNA repair protein. Recent studies have addressed the association between ERCC1 polymorphism and carcinogenesis. METHODS: We investigated a polymorphism of ERCC1 at nucleotide 19007 (C-->T, Asn118Asn) in 94 epithelial ovarian cancer patients, 102 endometrial cancer patients, and in 329 control subjects. RESULTS: We observed no evidence of associations between the C19007T ERCC1 polymorphism and risk of epithelial ovarian or endometrial cancer, which had the same adjusted odds ratios of 0.91 (p = 0.711, 0.691 respectively). CONCLUSION: Our findings suggest that the C19007T ERCC1 polymorphism is unlikely to play an important role in epithelial ovarian or endometrial cancer in Korean women.

Elevation of cyclooxygenase-2 is related to lymph node metastasis in adenocarcinoma of uterine cervix.

In a previous study, we demonstrated that elevation of COX-2 is significantly associated with lymph node metastasis in squamous cell carcinoma (SCC) of cervix. The main objective of this study is to characterize the relationship between elevation of COX-2 and its possible clinical role in adenocarcinoma (AC) of cervix. Using immunohistochemistry, we examined COX-2 expression levels in 84 patients with AC of uterine cervix [71 ACs, 13 adenosquamous carcinomas (ASCs)]. Elevation of COX-2 was correlated with clinicopathological variables and p53 expression, as detected by immunohistochemistry. Elevation of COX-2 was detected in 13.0% (11 of 84) of the tumors. Elevation of COX-2 was significantly correlated with histologic type (AC 8.5% vs. ASC 38.5%, P=0.011). Both tumor stage and lymph node metastasis were correlated with elevation of COX-2 with a borderline significance (P=0.062 and 0.068, respectively). Elevation of p53 was not associated with elevation of COX-2. The association between lymph node metastasis and elevation of COX-2 was stronger in cases of AC than in cases of ASC (28.4 vs. 4.3%, P=0.023). According to the results of univariate analysis, elevation of COX-2 was significantly associated with decreased overall survival (P=0.003, log-rank test). However, multivariate analyses revealed that only tumor stage was independently associated with overall survival, suggesting that elevation of COX-2 itself may not be an independent prognostic factor. The present study shows that elevation of COX-2 may contribute to lymph node metastasis in AC of uterine cervix. This suggests that the potential therapeutic role of COX-2 inhibitors should be validated, not only in SCC, but also in AC of uterine cervix.

Steroid receptor expressions in endometrial cancer: clinical significance and epidemiological implication.

The evaluation of expression levels of the estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer is a very common procedure in modern practice. However, the significance of such tests remains controversial, and the evaluation of the status of steroid receptors seems to be a more thoroughly justified practice. The present study was carried out with 145 endometrial cancer patients, all of whom had undergone operations at the Seoul National University Hospital, from 1993 to 2002. Paraffin-embedded tissue blocks were sectioned and immunostained with monoclonal anti-ER and anti-PR antibodies. Clinicopathological variables were also analyzed, with 10% cutoff values for ER and PR positivity. A multivariate Cox regression analysis was performed in order to estimate the influences of several clinicopathological and immunohistochemical covariates on patient survival. Forty seven specimens (32.4%) stained as ER positive, and 110 (75.9%) stained as PR-positive. Patients with PR-positive tumor tended to be both younger and more obese than patients with PR-negative tumors (P=0.020, 0.016). Well-differentiated tumors were found to be positive for ER or PR more frequently (P=0.015, <0.001). ER or PR-positive tumors exhibited significantly less myometrial invasion (P=0.042, 0.002). However, multivariate Cox regression analyses revealed that the expressions of ER and PR were not significantly associated with patient survival, and only advanced FIGO stage constituted an independent prognostic factor. Our results suggested that the evaluation of steroid receptors might prove helpful prior to surgery. Low ER and high PR values suggest that racial differences and/or sequential loss of receptors during carcinogenesis might be involved in the expression of steroid receptors in cases of endometrial cancer.

Association between excision repair cross-complementation group 1 polymorphism and clinical outcome of platinum-based chemotherapy in patients with epithelial ovarian cancer.

ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents. In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn (C -> T) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively. Using the SNapShot assay, we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients. Platinum-resistance was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. Although not significant, platinum-resistance was less frequently observed in patients with the C/T+T/T genotype (P=0.064). Multivariate analysis showed that the C/T+T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer (odds ratio 0.17, 95% confidence interval 0.04-0.74, P=0.018, Fisher's exact test). No significant correlation was observed between overall survival and the ERCC1 polymorphism. Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients. However, these findings require prospective confirmation.