Hyo Pyo Lee

Preoperative staging of uterine cervical carcinoma: comparison of CT and MRI in 99 patients.

Objective The aim of this study was to compare CT and MRI at 0.5 T in the preoperative staging of uterine cervical cancer in a large series of patients. Materials and Methods Ninety-nine patients with uterine cervical carcinoma underwent CT, MRI, and surgical exploration. Results Both CT and MR findings were compared using surgical-pathologic findings as gold standards. Magnetic resonance imaging was superior to CT in tumor detection (sensitivity 75 vs. 51%, p < 0.005), in parametrial evaluation (accuracy 87 vs. 80%, p < 0.005), in overall tumor staging (accuracy 77 vs. 69%, p < 0.025), and in pelvic lymph node evaluation (accuracy 88 vs. 83%, p < 0.01). Magnetic resonance imaging had an accuracy of 76% in assessment of the thickness of cervical stromal invasion. Conclusion Magnetic resonance imaging was superior to CT in preoperative staging of uterine cervical carcinoma and MRI should be used instead of CT for preoperative staging of this disease.

Detection of deep myometrial invasion in endometrial carcinoma: comparison of transvaginal ultrasound, CT, and MRI.

Objective The aim of this study was to compare the accuracy of transvaginal US (TVUS), CT, and MRI in detecting deep myometrial invasion in endometrial carcinoma. Materials and Methods Twenty-six patients with endometrial carcinoma were evaluated with TVUS, CT, and MRI. The depth of myometrial invasion was estimated in each examination. The invasion depth was categorized into no/superficial and deep and was compared to surgical and pathologic findings. Results At pathologic examination, the depth of myometrial invasion was no/superficial in 16 patients and deep in 10. The accuracy/sensitivity/specificity of TVUS, CT, and MRI in detecting deep myometrial invasion were 69/50/81, 61/40/75, and 89%/90%/88%, respectively. The sensitivity and accuracy of MRI in detecting deep myometrial invasion were significantly higher than those of TVUS and CT (p = 0.049 for both sensitivity and accuracy). Conclusion We recommend MRI instead of CT or TVUS for the evaluation of the depth of myometrial invasion in endometrial carcinoma.

Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite‐modification technique and methylation‐specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms.

Interleukin-10 promoter polymorphisms and cervical cancer risk in Korean women

The aims of this study were to determine whether polymorphisms of the interleukin (IL)-10 promoter might be associated with an increased risk of cervical cancer, and further whether systemic IL-10 concentration might be influenced by the genotypes in Korean women. Peripheral blood samples from patients with invasive cervical cancer (ICC, n=144) and non-cancer controls (NCC, n=179) were used to detect three biallelic IL-10 promoter polymorphisms at -1082, -819, and -592 sites by polymerase chain reaction-restriction fragment length polymorphism assay using MnlI, MaeIII and RsaI, respectively. The IL-10 serum concentration was measured with enzyme-linked immunosorbent assay. We compared the distribution of genotypes in both groups, evaluated the serum IL-10 level according to the genotypes, and analyzed the association of these polymorphisms with the risk of cervical cancer. The genotype at the -1082 site exhibited only the *A homozygote, and only two haplotypes were found in Korean women, one being -1082*A/-819*T/-592*A (ATA) and the other -1082*A/-819*C/-592*C (ACC). No association was found for IL-10 promoter polymorphisms among the ICC patients in comparison with the NCC subjects. The risk of cervical cancer was not increased in either genotype and the IL-10 serum concentration was not influenced by the genotypes in either group. Polymorphisms of the IL-10 promoter do not appear to be associated with cervical cancer risk or systemic IL-10 production in Korean women.

Multiple HPV infection in cervical cancer screened by HPVDNAChip.

This study determined the distribution of high-risk HPV type infection in cervical cancer using newly developed oligonucleotide chips (HPVDNAChips). The study subjects included 80 cases of cervical neoplasia and 746 controls with a normal Pap smear. For HPV genotyping, the commercially available HPVDNAChips was used. The risk of cervical cancer was increased in women with a family history of cervical cancer (adjusted OR=2.3, 95% CI: 0.92-6.17) and in smokers (adjusted OR=3.2, 95% CI: 1.45-7.06). There was also a trend of increased risk with the number of full term pregnancies (P(for trend)<0.001). There were only 7.2% (54 of 746) infected high-risk HPV types in the control, whereas 54.5% (six of 11) and 76.5% (52 of 68) were infected in the CIN and cervical cancer, respectively. Multiple HPV infection was observed in 0.5% (three of 592) of the control group but in 9.1% (seven of 77) of cases. Multivariate analysis revealed that subjects infected with multiple HPV types had a 31.8-fold (95% CI: 7.50-134.75) higher risk of cervical cancer, while the single HPV type had a 19.9-fold increased risk (95% CI: 10.90-36.18) (P(for trend)<0.001). These results show that the detection and typing of HPV infection by HPVDNAChip can be a useful in clinical applications because it provides information on multiple infections and the types of HPV in addition to HPV infection status.

Comparing the accuracy of ThinPrep Pap tests and conventional Papanicolaou smears on the basis of the histologic diagnosis: a clinical study of women with cervical abnormalities.

OBJECTIVE To confirm that the ThinPrep Pap test (TP) is as effective as or more effective than the conventional Papanicolaou smear (CS) in detecting epithelial cell abnormalities in a population with cervical abnormalities. STUDY DESIGN In a blinded, split-sample, matched-pair study, a CS was prepared using a cytobrush, and then TP slides were prepared from the remainder of the sample. All slides were evaluated as defined and classified by the Bethesda System. The results of the two cytologic tests were compared in 483 women relative to the histologic diagnoses of subsequent colposcopically directed cervical biopsies in 158 cases. RESULTS The cytologic diagnoses from the two methods agreed exactly in 91.4% of cases. The comparison between the two cytologic diagnoses with reference to the histologic diagnosis of subsequent colposcopically directed cervical biopsies showed that TP was significantly more specific for diagnosing lesions than was CS. The sensitivity of the two methods was equivalent. CONCLUSION In a population with cervical abnormalities, TP is more specific than and as effective as CS in detecting cervical epithelial cell abnormalities. TP improved the specificity of disease detection by reducing the atypical squamous cells of undetermined significance category and/or false positive cases.

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.

Interleukin-1 Beta -511 Polymorphism and Risk of Cervical Cancer

Cervical cancer is almost invariably associated with infection by human papillomavirus. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The IL1B gene, encoding IL-1β cytokine, contains several single nucleotide polymorphisms. One of them which is in the positions -511 (C-T) related with promoter region has been associated with increased IL-1β production and with increased risk of developing a number of inflammatory diseases and gastric carcinoma. We assessed the association between the IL1B -511 polymorphism and cervical cancer risk in a hospital-based case-control study among 546 Korean women (182 cases; 364 age-matched controls). The allele frequencies of the case subjects (C, 0.42; T, 0.58) were not significantly different from those of control subjects (C, 0.43; T, 0.57). Control subjects were in Hardy-Weinberg equilibrium. The carriers with -511 C/T or T/T genotypes were at higher risk of cervical cancer with odds ratio of 2.42 (95% CI 1.31-4.46, p<0.005). However, there was no difference of cervical cancer risk between C/T heterologous genotypes and T/T homologous genotypes. In conclusion, in Korean population, IL1B -511 C/C genotypes were significantly associated with a decreased risk of cervical cancer.

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

Abstract:  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.

Lack of Association of the Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Gene Polymorphism with Risk of Cervical Cancer in Korean Population

Abstract:  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 Ser608Leu 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.