Publications (9)12.19 Total impact
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Article: Human Papillomavirus Type 16 Causes Larger Colposcopic Lesions Than Other HPV Types in Patients With Grade 3 Cervical Intraepithelial Neoplasia.
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ABSTRACT: OBJECTIVE: Recent studies have shown that human papillomavirus (HPV) type 16 causes more definite visual abnormalities on cervigram than other HPV types and is thus easier to evaluate colposcopically. We examined factors, including HPV-16, related to colposcopic lesions in patients with grade 3 cervical intraepithelial neoplasia (CIN 3). METHODS: A retrospective chart review included 108 women with CIN 3 who underwent the loop electrosurgical excision procedure (LEEP). Lesions were assessed according to the number of cervical quadrant(s) involved by colposcopy, dichotomized as 2 or fewer or 3 or more quadrants involved. The Hybrid Capture 2 (HC2) test and HPV DNA chip assay (MyGene Co, Seoul, Korea) were used to detect HPV before punch biopsy or loop electrosurgical excision procedure. The type of HPV was dichotomized as HPV-16 or other (including negative cases). The HC2 viral load cutoff was 300 relative light units. Cytology was dichotomized as (1) low grade, less than, or equal to low-grade squamous lesions; or (2) high-grade, with high-grade squamous lesions or worse. Age and menopausal status were also assessed. RESULTS: The mean (SD) age of the 108 women was 41.9 (10.7) years (range = 22-76 y). Seventy-one (65.7%) had lesions involving 2 quadrants or fewer and 37 (34.3%) had lesions involving 3 quadrants or more. Multiple logistic regression revealed that larger lesions (≥3 quadrants involved) were significantly associated with HPV-16 (p = .032, odds ratio [OR] = 2.552, 95% confidence interval = 1.085-6.000) but not with age, menopausal status, cytologic grade, or HPV HC2 viral load. CONCLUSIONS: Our data suggest that colposcopic lesions differ according to HPV type and that HPV-16 is associated with larger lesions, facilitating lesion detection by colposcopy.Journal of Lower Genital Tract Disease 01/2013; 17(1):1-5. · 1.07 Impact Factor -
Article: Early human papillomavirus testing predicts residual/recurrent disease after LEEP.
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ABSTRACT: The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse. We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse. Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (≥100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months. Margin involvement in conization specimens was a significant factor predicting residual/recurrent disease after LEEP. HPV test results at 3 and 6 months after treatment were comparable. Early 3-month follow-up testing after LEEP can offer timely information about residual/recurrent disease and alleviate patient anxiety early about treatment failure.Journal of Gynecologic Oncology 10/2012; 23(4):217-25. · 1.49 Impact Factor -
Article: Klotho inhibits the capacity of cell migration and invasion in cervical cancer.
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ABSTRACT: Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers. However, the mechanisms of Wnt activation in cervical cancer remain largely unknown. In the present study, we demonstrate that Klotho, a Wnt antagonist, is downregulated in invasive human cervical tumors and in a cell line we analyzed. Our data demonstrated that in vivo Klotho expression was not observed in invasive cervical carcinoma. In vitro restoration of Klotho expression in SiHa cells resulted in a decreased cell motility and invasiveness through upregulation of E-cadherin, downregulation of N-cadherin and reduced expression of MMP7 and -9. Ectopic expression of Klotho also reduced the expression of the epithelial-to-mesenchymal transition (EMT) transcription factors Slug and Twist. Furthermore, Klotho causes a significant inhibition of the Wnt/β-catenin pathway in cervical cancer cells, as supported by the expression of Wnt/β-catenin transcriptional target genes such as c-Myc and cyclin D1. Consequently, our findings demonstrate for the first time that Klotho regulates tumor invasion through the EMT process and provide novel mechanistic insights into the role of Klotho in cervical cancer progression and contribute to treatment for metastatic cervical cancer patients.Oncology Reports 06/2012; 28(3):1022-8. · 1.84 Impact Factor -
Article: Random biopsy after colposcopy-directed biopsy improves the diagnosis of cervical intraepithelial neoplasia grade 2 or worse.
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ABSTRACT: To evaluate the usefulness of additional random biopsies in the diagnosis of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse (CIN 2+) after colposcopy-directed biopsy. A retrospective chart review was performed in 107 women with satisfactory colposcopy results after colposcopy-directed biopsy with random biopsy for abnormal cervical cytological evaluation at Soonchunhyang University Hospital between April 2008 and November 2009. Random biopsies were performed at the cervical squamocolumnar junction in lesion-free quadrants of the cervix. Loop electrosurgical excision procedure conizations were performed in 59 women. Age, referral cytology, lesion size, human papilloma virus (HPV) viral load, and HPV type were analyzed as possible indicators of lesion severity detected using random biopsy. The mean age was 39.3 years (range = 21-72 y), and 96 (89.7%) women were premenopausal. Sixty-three women had CIN 2+; of those, 8 (12.7%) were diagnosed using random biopsies: 6 had high-grade squamous intraepithelial lesions; 1 had low-grade squamous intraepithelial lesions; and 1 had atypical squamous cells of undetermined significance. Lesions diagnosed as CIN 2+ using random biopsies were significantly correlated with high-grade cytology (p <.001) and lesion size (p <.001) but not age (cutoff = 40 years), HPV viral load (cutoff = 300 relative light units; Hybrid Capture 2), or HPV genotype. Of 59 patients who underwent loop electrosurgical excision procedure conization, the disease severity of 9 (15.3%) cases was upgraded 1 or more grades, compared with the punch biopsy results. The detection of CIN 2+, particularly high-grade cytological abnormalities and large lesion size, can be increased by additional random biopsies after satisfactory colposcopy. Loop electrosurgical excision procedure conization can detect lesions not detected by punch biopsy.Journal of Lower Genital Tract Disease 10/2010; 14(4):346-51. · 1.07 Impact Factor -
Article: The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma
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ABSTRACT: Abstract Background Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma. Results Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non- KLOTHO -expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active β-catenin levels, suppression of T-cell factor/β-catenin target genes, such as c-MYC and CCND1 , and inhibition of colony growth. Conclusions Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.Molecular Cancer. 01/2010; -
Article: The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma.
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ABSTRACT: Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma. Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non-KLOTHO-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active beta-catenin levels, suppression of T-cell factor/beta-catenin target genes, such as c-MYC and CCND1, and inhibition of colony growth. Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.Molecular Cancer 01/2010; 9:109. · 3.99 Impact Factor -
Article: Angiomyofibroblastoma of the vulva: sonographic and computed tomographic findings with pathologic correlation.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 10/2009; 28(10):1417-20. · 1.25 Impact Factor -
Article: Factors associated with HPV persistence after conization in patients with negative margins.
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ABSTRACT: The clearance rate of human papillomavirus (HPV) after conization is generally high, although some HPV infections persist. We investigated the factors that affect the clearance of HPV after conization in patients with negative margins. We retrospectively analyzed 77 patients (mean age 39.9 years, range 25 to 51 years) with CIN 2/3 who underwent loop electrosurgical excision procedure (LEEP) conization with negative margins. All patients had a Pap smear and high-risk (HR) HPV testing using Hybrid Capture II system and HPV DNA chip before conization. We used>/=1 relative light units (RLUs) as the cutoff for persistence of HPV after conization. High-risk HPV was detected in 73 of 77 (94.8%) patients before conization. At the 6-months follow-up, the high-risk HPV was eliminated in 60 of 73 (82.2%) patients. The HPV persistence rate after conization was 17.8% (13/73). Univariate analysis showed that persistent HPV infection after conization with negative margins was more likely to occur when the pretreatment viral load was high (RLU/positive control >100 (p=0.027) and the HPV was type 16 (p=0.021). Logistic regression analysis showed that preoperative HPV type 16 infection was the only significant independent factor (p=0.021) for HPV persistence out of age, cytology, punch biopsy histology, HPV viral load, and conization histology. Conization effectively removes HR-HPV infection. HPV type 16 infection before conization was significantly related to HR-HPV persistence after conization with negative margins. Therefore, patients with HPV 16 infection before conization need to be followed closely.Journal of Gynecologic Oncology 06/2009; 20(2):91-5. · 1.49 Impact Factor -
Article: A case of primary non‐Hodgkin's lymphoma of the myometrium with involvement of bilateral ovaries
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ABSTRACT: We report a case of primary non-Hodgkin's lymphoma (NHL) of the uterine body with involvement of bilateral ovaries. A 67-year-old woman had explolaparotomy under the provisional diagnosis of uterine leiomyoma. Enlargements of the uterine body as a leiomyoma and bilateral ovaries were noted in the operation field. The frozen section diagnosis of the uterine wall mass was malignant lymphoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was carried out. The pathologic study with immunohistochemical stains confirmed primary NHL of the diffuse large B-cell type of the myometrium with involvement of bilateral ovaries. To the best of our knowledge, the primary lymphoma of the myometrium with involvement of bilateral ovaries has not been reported previously in the literature.Basic and Applied Pathology 03/2009; 2(1):40 - 43.
Top co-authors
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Institutions
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2012–2013
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Soonchunhyang University
South Korea
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2010–2012
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Sookmyung Women's University
Seoul, Seoul, South Korea
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