ROLE OF 5’-CpG ISLAND HYPERMETHYLATION OF THE FHIT GENE IN CERVICAL CARCINOMA

기경도,동서연,송동화,이종민,지성길,이선경 대한부인종양학회 2008 Journal of Gynecologic Oncology Vol.19 No.2

Objective: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer. Methods: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing. Results: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics. Conclusion: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort. Objective: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer. Methods: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing. Results: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics. Conclusion: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort.

Significance and Expression of Aquaporin 1, 3, 8 in Cervical Carcinoma in Xinjiang Uygur Women of China

Shi, Yong-Hua,Chen, Rui,Talafu, Tuokan,Nijiati, Rehemu,Lalai, Suzuke Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Overexpression of several aquaporins (AQPs) has been reported in different types of human cancer but their role in carcinogenesis, for example in the cervix, have yet to be clearly defined. In this study, expression of AQPs in cervical carcinomawas investigated by real-time PCR, immunofluorescent and immunohistochemical assays and evaluated for correlations with clinicopathologic variables. AQP1, 3, 8 exhibited differential expression in cervical carcinoma, corresponding CIN and mild cervicitis. AQP1 was predominantly localized in the microvascular endothelial cell in the stroma of mild cervicitis, CIN and cervical carcinoma. AQP3 and AQP8 were localized in the membrane of normal squamous epithelium and carcinoma cells, local signals being more common than diffuse staining. AQP1 and AQP3 expression was remarkably stronger in cervical cancer than in mild cervicitis and CIN2-3 (P<0.05). AQP8 expression was highest in CIN2-3 (91.7%), but levels in cervical carcinoma were also higher than in mild cervicitis. AQP1, AQP3, AQP8 expression significantly increased in advanced stage, deeper infiltration, metastatic lymph nodes and larger tumor volume (P<0.05). Our findings showed that AQPs might play important roles in cervical carcinogenesis and tumour progression in Uygur women.

Opportunities for 2-[18F] Fluoro-2-Deoxy-D-Glucose PET/CT in Cervical-Vaginal Neuroendocrine Carcinoma: Case Series and Literature Review

Yin Lin,Wan Y. Lin,Ji A. Liang,Yu Y. Lu,Hsin Y. Wang,Shih C. Tsai,Chia H. Kao 대한영상의학회 2012 Korean Journal of Radiology Vol.13 No.6

Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation. Objective: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. Materials and Methods: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Results: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. Conclusion: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.

자궁경부암에서 Cdc25A, Cdc25B 및 Cdc25C의 발현

김혜연 ( Hye Yeon Kim ),김재욱 ( Jae Wook Kim ),김세광 ( Sei Kwang Kim ),김영태 ( Young Tae Kim ),김재훈 ( Jae Hoon Kim ),김성훈 ( Sung Hoon Kim ),김상운 ( Sang Wun Kim ),윤보성 ( Bo Sung Yoon ),남은지 ( Eun Ji Nam ),조혜진 ( Hye 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.10

목적: 본 연구는 자궁경부암에서 세포주기 조절인자인 cell division cycle (Cdc) 25A, Cdc25B 및 Cdc25C 발현 양상을 정량적으로 측정하여 이들이 자궁경부암의 발암과정에서 어떠한 역할을 하는지를 규명하며 아울러, 자궁경부암의 여러 다른 임상적 및 병리학적 예후 인자와 상관관계가 있는지를 연구하고자 하였다. 연구 방법: 본원 산부인과에서 2000년 2월부터 2005년 3월까지 수술적 치료를 받은 환자를 대상으로 하여 신선 자궁경부 조직을 얻었다. 역전사 중합요소 연쇄 반응과 Western blot analysis를 이용하여 각각 Cdc25A, Cdc25B 및 Cdc25C의 mRNA와 단백질 발현 양상을 확인하였다. 결과: 자궁경부암 조직에서의 Cdc25A, Cdc25B 및 Cdc25C의 mRNA 발현은 정상 자궁경부 조직보다 모두 통계학적으로 유의하게 높았으며 (p=0.02, 0.01, 0.02), Cdc25A, Cdc25B 및 Cdc25C의 단백질 발현 양상도 자궁경부암 조직에서 정상 자궁경부 조직에 비해 모두 통계학적으로 유의하게 높은 결과를 보였다 (p=0.01, 0.02, 0.01). 또한 자궁경부암에서의 Cdc25A, Cdc25B 및 Cdc25C의 mRNA 발현과 단백질 발현을 임상적 및 병리학적 예후 인자들에 따라 비교한 결과 환자의 연령과 Cdc25B mRNA 발현 (p=0.03), 세포 형태와 Cdc25C mRNA 발현 (p=0.04) 사이에서는 통계학적으로 유의한 상관관계를 보였으나 그 외의 인자들인 세포아형태, 혈청내 squamous cell carcinoma antigen (SCC Ag) 수치, 유세포 분석법을 통한 DNA flow cytometry 결과, 림프절 전이, 림프혈관 침범, 인유두종 바이러스 감염 등과는 통계학적으로 유의한 상관 관계를 보이지 않았다. 결론: 본 연구 결과에 따르면 Cdc25A, Cdc25B 및 Cdc25C가 대조군인 정상 자궁경부 조직에 비해 자궁경부암 조직에서 통계학적으로 유의하게 높게 발현됨을 확인할 수 있었다. 따라서, 자궁경부암의 발생기전에 Cdc25A, Cdc25B 및 Cdc25C가 중요한 역할을 할 가능성을 제시하였다. 또한 Cdc25A, Cdc25B 및 Cdc25C의 mRNA와 단백질 발현은 환자의 연령이 50세 이상인 경우에 Cdc25B mRNA 발현이 유의하게 높았으며 (p=0.03), 세포형태에 따라 분류하였을 때 편평상피세포암에서 Cdc25C mRNA 발현이 통계학적으로 유의하게 높았다 (p=0.04). 그러나, 다른 예후 인자들과는 통계학적으로 유의한 상관관계를 보이지 않았다. 향후 Cdc25A, Cdc25B 및 Cdc25C가 자궁경부암의 유용한 예후 인자로 사용되기 위해서는 향후 생존율과 연관된 연구가 추가로 뒷받침되어야 할 것으로 생각된다. Objective: This study was undertaken to quantitatively detect Cdc25A, Cdc25B and Cdc25C in cervical carcinoma and determine the relationship between the expression of mRNA and protein of cell division cycle (Cdc)25 phosphatase and various clinicopathologic prognostic factors of cervical carcinoma. Methods: 39 patients diagnosed with cervical carcinoma between February 2000 to March 2005 and 10 patients with benign gynecologic disease were enrolled in this study. A reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to analyze the expression of Cdc25 phosphatase mRNA and protein in fresh invasive cervical cancer tissue and normal cervix tissue. Results: The mRNA expressions of Cdc25A, Cdc25B and Cdc25C in the cancer tissues were significantly greater than in the control (p=0.02, 0.01, 0.02), respectively. A Western blot analysis yielded same results (p=0.01, 0.02, 0.01). There were also significant relationships between the age and the Cdc25B mRNA expression (p=0.03), between the cell type and the Cdc25C mRNA expression (p=0.04). However, other clinicopathologic prognostic factors including stage, subtype, SCC Ag level, DNA flow cytometry, lymph node metastasis, lymphovascular space invasion and HPV positivity were not statistically significant. Conclusion: Our results show that Cdc25A, Cdc25B and Cdc25C expression levels were significantly greater in cervical cancer patient group than in those of control group. Thus Cdc25 phosphatase might play an important role in carcinogenesis of cervical carcinoma. Further studies based on the correlation between Cdc25 phosphatase and survival rate would be need to support Cdc25 phosphatase as a prognostic factor of cervical carcinoma.

TLR9 Expression in Uterine Cervical Lesions of Uyghur Women Correlate with Cervical Cancer Progression and Selective Silencing of Human Papillomavirus 16 E6 and E7 Oncoproteins in Vitro

Hao, Yi,Yuan, Jian-Ling,Abudula, Abulizi,Hasimu, Axiangu,Kadeer, Nafeisha,Guo, Xia Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Cervical cancer is listed as one of high-incidence endemic diseases in Xinjiang. Our study aimed to evaluate the expression of TLR9 in uterine cervical tissues of Uyghur women and examine associations with clinicopathological variables. We further characterized the direct effects of TLR9 upon the selective silencing of human papillomavirus (HPV) E6 and E7 oncoprotein expression in HPV 16-positive human cervical carcinoma cells treated with siRNA in vitro. Materials and Methods: Immunohistochemistry was applied to evaluate TLR9 expression in 97 formalin-fixed paraffin-embedded cervical samples from Uyghur women; 32 diagnosed with cervical squamous cell carcinomas (CSCC), 14 with low-grade cervical intraepithelial neoplasias (CINI), 10 medium-grade (CINII), 24 high-grade (CINIII), and 17 chronic cervicitis. $BLOCK-iT^{TM}$ U6 RNAi Entry Vector $pENTR^{TM}$/U6-E6 and E7 was constructed and transfected the entry clone directly into the mammalian cell line 293FT. Then the HPV 16-positive SiHa human cervical carcinoma cell line was infected with RNAi recombinant lentivirus. RT-PCR and Western blotting were used to determine the expression of TLR9 in both SiHa and HPV 16 E6 and E7 silenced SiHa cells. Results: Immunohistochemical staining showed that TLR9 expression was undetectable (88.2%) or weak (11.8%) in chronic cervicitis tissues. However, variable staining was observed in the basal layer of all normal endocervical glands. TLR9 expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with the histopathological grade in the following order: chronic cervicitis (2/17, 11.8%) <CINI (4/19, 28.6%) <CINII (3/10, 30.0%) <CINIII (12/24, 50.0%) <CSCC (17/32, 53.1%) (p<0.05), but not with tumor differentiation. RT-PCR and Western blotting showed that TLR9 expression was upregulated in HPV16 E6 and E7 silenced SiHa cells at both mRNA and protein levels. Conclusions: TLR9 expression increases according to the histopathological grade of cervical pathological process. HPV E6 and E7 oncoprotein have negative effects on the expression and function of TLR9.

자궁경부 소세포암종의 방사선치료

정은지(Eun Ji Chung),이용희(Yong Hee Lee),김귀언(Gwi Eon Kim),서창욱(Chang Ok Suh) 대한방사선종양학회 1997 Radiation Oncology Journal Vol.15 No.4

목 적 : 자궁경부 소세포암종으로 진단되어 방사선치료를 받은 환자에서 조직병리학적인 재검사를 시행하여 조직병리학적 특성을 알아보고, 환자 및 종양의 특징, 방사선치료 후의 치료 성적 등을 조직병리학적 유형에 따라 후향적으로 비교 분석해 보았다. 대상 및 방법 : 1981년 10월부터 1995년 4월까지 연세의대 연세암센터 치료방사선과에서 자궁경부암으로 방사선치료를 받은 환자 총 2890명 중 조직학적 유형이 소세포암종이었던 환자는 60명으로 2.08%였다. 타병원에서 조직검사 및 병기 결정 후 방사선치료 만을 위해 전과되었던 36예에서는 자궁경부 생검 조직을 확보할 수 없었고, 이들을 제외한 24명에서 조직에 대한 병리학적 재검사가 가능하여 H & E 염색 및 신경내분비 표지인 neuron-specific enolase(NSE), chromogranin, synaptophysin, Grimelius 면역조직화학 염색을 시행하였다. 이들 24예의 환자 및 종양의 특성, 방사선치료에 대한 반응, 치료 실패 양상, 5년 생존율 및 5년 무병 생존율 등을 후향적으로 분석하였다. 결 과 : H & E 염색 및 4가지 neuroendocrine marker 검사 후 13예는 신경내분비암종으로 진단되었고 11예는 소세포 유형의 편평상피암종으로 진단되어 병리학적으로 크게 2가지 군으로 분류하였다. 신경내분비암종으로 분류된 13예 중 5예는 중등도 이상으로 분화가 좋은 편이었으나 8예는 분화가 나쁘거나 미분화되었다. 전체 24예 대상 환자들의 연령은 23-79세로 중앙 연령치 54세였으며 FIGO 병기 분포는 Ib 8예(33.3%), IIa 1예(4.2%), IIb 11예(45.8%), IIIa 2예(8.3%), IIIb 1예(4.2%), IV 1예(4.2%)로 병기 I- II가 20예로 대다수를 차지하였다. 골반 림프절에 전이가 있었던 환자가 5예(20.8%) 있었는데 이 중 3예는 수술후 조직학적으로 확인되었고(2예는 근치적 수술, 1예는 골반 림프절 생검) 다른 2예는 전산화 단층 촬영상 골반 림프절이 커져 있어 전이로 판단되었다. 이들 2가지 병리학적 분류군에 따라 환자 및 종양의 특성을 비교해 보았는데 특별한 차이는 발견할 수 없었으며, 방사선치료에 대한 반응, 치료 실패 양상, 5년 생존율 및 5년 무병 생존율 등의 치료 결과를 비교해 보았을 때 치료 실패 양상에 있어서 소세포형의 편평상피암종에서는 원격 전이가 2예(18.2%)인데 반해 신경내분비암종에서는 6예(46.2%)로 신경내분비암종(neuroendocrine carcinoma)에서 원격 전이율이 높았으나 환자 수가 적어 통계학적인 유의성은 없었다(P>0.05). 결 론 : 병리조직학적 재검사가 가능하였던 24예의 자궁경부 소세포암종 환자 중 13예가 신경내분비암종으로 진단되었으며 나머지 11예는 소세포형의 편평상피암종으로 분류되었는데 환자 및 종양의 특징, 방사선치료 성적을 비교해 볼 때 신경내분비암종에서 원격 전이가 호발하였으나(46.2% vs. 18.2%), 5년 생존율과 5년 무병 생존율의 차이는 없었다. 이런 결과로 자궁경부에서 발생한 소세포암종 중 신경내분비암종의 경우는 원격 전이가 많으므로 방사선치료, 수술 등의 국 소 치료와 더불어 적절한 항암화학요법을 추가하여 치료 결과를 증진시킬 수 있으리라 생각한다. Purpose : This study was performed to identify the histopathologic feature by the reevaluation of the pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas (2.08%). Among them thirty six patients were transferred from other hospitals, the biopsy specimens of those patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin, synaptophysin and Grimelius stain). And we also evaluate the patients and tumor characteristics, response to radiation, patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas (13/24=54.2%) and eleven tumors were squamous carcinomas, small cell type (11/24= 47.8%) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma. Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight patients had FIGO stage IB disease, 12 had stage II, 3 had stage III and one had stage IV disease. Pelvic lymph node metastases were found in five patients (20.8%), three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics, response to radiation, 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma patients (6/13:46.2%) than in small cell type of squamous carcinoma patients (2/11:18.2%), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : 54.1%) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neuroendocrine carcinoma was greater than those of the small cell type of squamous carcinoma (46.2% vs. 18.2%). But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

자궁경부암에서 혈관 내피 성장인자 ( VEGF ) 및 VEGF Mrna 의 발현에 대한 연구

이선경(Seon Kyung Lee),김승보(Seung Bo Kim),지성길(Sung Gil Chi),염윤석(Yoon Seok Yum),이주희(Ju Hee Lee) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.1

N/A Objective : Angiogenesis, the formation of blood vessels by sprouting from pre-existing ones, is essential for the growth of solid tumors beyond 2~3mm in diameter and for tumor metastasis. Vascular endothelial growth factor (VEGF), is known as vascular permeability factor(VPF) and mediates vascularization and tumor-induced angiogenesis. This study examined the potential of growth, invasion, and metastasis of uterine cervical carcinomas associated with neovascularization. Methods : From January 1996 to December 1999, at the Department of Obstetrics and Gynecology, Kyung-Hee University Hospital, 37 uterine cervical carcinomas and 7 normal cervical tissues were obtained and the samples were immediately frozen and stored at -70℃. Immunohistochemical staining for VEGF was carried out to study VEGF localization, and the levels of VEGF subtype mRNAs were determined by quantitative RT-PCR in specimens. The relation between VEGF subtypes expression of cervical cancers was analysed. Results : The positive staining for VEGF is seen dominantly in the cytoplasm of the cancer cells, and faintly in interstitial cells. The intensity of staining was stronger in squamous carcinomas than in adenocrcinomas, but there was no significant difference (p>0.05). Quantitative RT-PCR analysis demonstrated significantly increased VEGF121/VEGF165 mRNA expression levels (>0.56/>0.72) in 21 (56.8%) and 15 (40.5%) of 37 cervical carcinomas comparing to control groups (mean: 0.28/0.36). There was no obvious relationship between VEGF121/VEGF165 mRNA expression levels and the clinical parameters examined including age, pathology, differentiation, tumor size, lymphovascular space invasion, LN involvement and invasion depth except clinical stage (p<0.05). Conclusions : The overexpression of VEGF mRNA may be an important contributing factor in cervical carcinomas. There is no significant differenece of VEGF mRNAs levels according to clinical parameters, so it seems that the expression of VEGF is involved in the promotion of angiogenesis on cervical cancer and plays an important role in early invasion.

자궁경부암종에서 인유두종 바이러스 감염, p16INK4A와 p18INK4C유전자 변이 및 세포주기조절 단백의 발현

권경익(Kyung Ik Kwon),김상표(Sang Pyo Kim),서성일(Seong Il Suh),황미열(Mi Yeul Hwang),백원기(Won Ki Baek),권건영(Kun Young Kwon),이상숙(Sang Sook Lee),조치흠(Chi Heum Cho) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.4

N/A Objective : We analyzed the gene status of p16INK4A, p18INK4C, the expression of cell cycle associated proteins (p16INK4A, p18INK4C, cyclin D1, CDK4, pRb, and p53), and human papillomavirus (HPV) infection to investigate whether the inactivation of these genes participated in carcinogenesis, and to evaluated the expression of cell cycle associated proteins and HPV infections. Methods : We examined forty-one primary cervical carcinomas (17 adenocarcinomas, 13 keratinizing squamous cell carcinomas, and 11 nonkeratinizing squamous cell carcinomas) using PCR, comparative multiplex PCR, PCR-SSCP, methylation-specific PCR, and immunohistochemistry. Results : Ninety percent of cervical carcinomas showed HPV infection. HPV type 16 was detected in 41% and HPV type 18 was found in 44%. Homozygous deletions at p16INK4A gene were observed in 2 cases, but the mutation of p16INK4A and alterations of p18INK4C gene were not detected. The promoter hypermethylation for p16INK4A in nine cases (31%) of 29 cervical carcinomas was found. Expression of p16INK4A protein was observed in 93% and p18INK4C protein expression was noted in 78%. Positive immunostaining for cyclin D1 was only identified in 5%, whereas positive immunostaining for CDK4 was observed in 95%. Expression of pRb protein was found in 93% and p53 protein in 24% of cervical carcinomas. Conclusion : These results suggest that high risk HPV infections and methylation of the p16INK4A promoter region seem to play an important role in the pathogenesis of cervical carcinomas. Alterations of p18INK4C gene and cyclin D1-CDK4 pathway does not contribute significantly in the cervical carcinogenesis.

자궁경부암에서 MAGE 3 유전자 산물의 발현

강태경(Tae Kyoung Kang),서남원(Nam Won Seo),김도형(Do Hyung Kim),안은모(Un Mo Ahn),여태홍(Tae Hong Yeo),김준홍(Jun Hong Kim),안선의(Sune Ie Ahn),김동휘(Dong Hwi Kim),박은동(Un Dong Park) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.3

N/A Objective: The human MAGE 3 gene encodes tumor specific antigens that are recognized by autologue cytotoxic T lymphocytes (CTL). The MAGE 3 gene is expressed not only in melanoma but in the other malignant tumors as well. There is, however, little information on the expression of the gene in uterine cervical carcinomas. The author thus studied the expression of the MAGE 3 gene products in uterine cervical carcinoma and discuss the possibility of specific immunologic diagnosis using MAGE 3 gene products. Methods: The expression of MAGE 3 gene product in 17 normal tissues of the cervix, 32 cervical intraepithelial neoplasia (8 CINⅠ, 10 CINⅡ, 14 CIS), and 43 invasive cervical carcinomas was studied by immunohistochemistry using anti-MAGE 3 mAb 57B in paraffin sections. Results: No expression of MAGE 3 gene product was detected in normal cervical tissues and in cervical intraepithelial neoplasias. The expression of MAGE 3 gene product was detected in 30.2% (13/43) of invasive cervical carcinomas. The MAGE 3 gene product was stained as a cytoplasmic protein in cancer cells. No statistically significant differences were observed between MAGE 3 gene product expression status and clinicopathologic parameters. Conclusions: The MAGE 3 gene products was expressed in invasive cervical carcinoma tissues.

자궁경부 상피내암종과 침윤성 편평세포암종에서 인체 유두종바이러스 감염과 bcl-2단백 발현 및 Apoptosis와의 관련성

정명자,장규윤,문우성,강병재,이동근 대한병리학회 1999 Journal of Pathology and Translational Medicine Vol.33 No.9