자궁경부암에서 p53 유전자의 변이와 MDM2 증폭에 관한 연구

장미경(MK Chang),이선경(SK Lee),지성길(SG Jee) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.5

Mutation of the p53 tumor suppressor gene is one of the most commonly found genetic alteration in human cancer. The E6 gene product from human papillomavirus (HPV) 16 and 18 can inactivate the p53 protein by promoting its degradation via proteolytic ubiquitin system. But in HPV negative cervical carcinomas, many investigators have rarely found the p53 mutation. Still assuming that p53 inactivation is an essential step in development of HPV negative cervical cancer, alternative pathways have been discussed. MDM2 gene is a negative regulator of p53 protein activity, whereas p53 itself can stimulate MDM2 expression, thus forming a MDM2-p53 autoregulatory feedback loop. So, the author studied the presence of HPV-16/18 by PCR and the p53 mutation by PCR/SSCP and direct sequencing in 43 cases of primary cervical cancer. Furthermore, the author tried to define the MDM2 amplification by quantitative PCR, for evaluation of altenative pathway in p53 protein inactivation. In the results, the presence of HPV 16/18 were 32 cases and absence of HPV 16/18 were 11 cases.p53 mutations were shown in 8 cases. 4 cases were in HPV 16/18 positive cancers and the rest were in HPV-16/18 negative ones. Among the HPV-16/18 positive ones, there are three missence mutations at exon 6 and 7 and one frame shift mutations in exon 6. Among the in HPV-16/18 negative ones, there were two frame shift mutation in exon 5 and 7, one missence mutation in exon 8 and one deletion from exon 4 to 5. One amplification of the MDM2 gene was observed in HPV positive cervical cancers. According to this study results, it is rare to have p53 mutation or MDM2 amplification. The data shows that cervical cancer may be development in the p53 mutation and presence of HPV and in the absence of p53 mutation and HPV. So There may be additional mechanisms in the development of cervical cancer rather than p53 mutation and presence of HPV. For further clarification of the molecular mechanisms of cervical carcinogenesis,complete characterization of large number of tumor, possibly by automated technique, will be helpful.

자궁경부암에서 p53 억제 유전자 단백의 발현과 인유두종 바이러스감염과의 상관관계

장미경(MK Chang),이선경(SK Lee),김승보(SB Kim),이재현(JH Lee),이주희(JH Lee) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.12

We examined the expression of tumor suppressor gene product, p53 protein, immunohistochemically by using p53 monoclonal antibody and HPV type 16/18 infection by in situ hybridization of fluorescein-labelled probe in tissue obtained from 67 cases of the uterine cervical cancer. In this study, we analyzed that each data affect the prognosis of uterine cervical cancer, and examined the hypothesis of inverse correlation between the presence of HPV infection and the mutant p53 protein. The overall expression the p53 protein was 23.9%. The expression rate was increased with advancing clinical stage, and the large cell keratinizing type has higher expression rate than nonkeratinizing type(42.1% vs 18.4%, p=0.01). The infection rate of HPV type 16/18 was 70.1% and increased with advancing clinical stage, but other prognostic factors of cervical cancer were not correlated with p53 protein expression and HPV type 16/18 infection. Compared expression rate of p53 with HPV type 16/18 infection, there was significant correlation between HPV type 16/18 positive tumor and vegative expression of p53(p=0.043).

자궁경부에 발생한 Verrucous Carcinoma 1 례

장미경(MK Chang),최영일(YI Choi),진규섭(KS Jin),이선경(SK Lee) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.2

A vareity of unusual squamous cell carcinoma was first identified as a distinct entity by Ackermann in 1948 in lesion of the oral cavity, by Kraus and Perez-Mesa in 1966 in vulva, and in 1972 by Jennings in uterine cervix. This carcinoma is a highly differentiated variant of epidermoid carcinoma with a polypoid pattern of growth, extremely well differented cystic appearance and capacity for local invasion, but not metastatic spread and long recurrence-free survival after simple hysterectomy. There were numerous reports in literature describing lesion of genital verrucous carcinomas, but rare in uterine cervix. Authors present a case belived to be a verrucous carcinoma of cervix and review literature about this case.

근치적 자궁적출술을 시행한 침윤성 자궁경부암 환자 178 례에 관한 임상적조사

손종우(JW Shon),장미경(MK Chang),이선경(SK Lee) 대한산부인과학회 1993 Obstetrics & Gynecology Science Vol.36 No.11

Since the introduction of the Pap smear and colposcopy cervical cancers can be diagnosed and treated easily in their preinvasive state. Although theoretically cancer of the cervix should be detected and treated before becoming invasive disease, there are still too many women who develop invasive cancer of the cervix and require radical sugery and of radiation therapy During the period from Jan, 1,1983though Oct. 31,1991,178 women with invasve carcinoma of the uterine cervix were treated by radical hysterctomy and pelvic node dissection at the Department of Obstetrics and Gynecology, KyungHeeUniversity Hospital, Seoul Korea 1. The results were as follows: 1. The age distribution among the 178 patients ranged from 24 to 75 years. mostly at 50-59 years(34.1%)and 40-49 years (27.75). The mean age was 46.2%years 2. The frequent numer of pregnancies was 3-8 times(66.65)and the mean number of pergnancies was 6.1times. 3. In the distribution by histologic type, squamous cell carcinoma was 89.95 adenocarcinoma 7.9% and adenosquamous carcinoma was 1.1% 4. Among the 160cases of the invasive squamous cell carcinoma, the histologic subtypew were as follows: large cell nonkeratinizing type was 66.9% , large cell keratinizing type 28.15 and small cell type was 5.0% 5. The most frequent clinical symptoms of the invasive carcinoma of the uterine cervix were contact bleeding (37.7%)iregular vaginal bleeding(31.9%)and leukorrhea(10.1%) 6. According to their growth pattern, exophytic growth were 47.1% endophytic growth 16.0% eroced and ulcerative growth were 17.4%and 11.6% respectively 7. More than half of the invasive carcinoma of the uterine cervix postmenopausal women (52.2%)and premenopausal patients were 34.0% 8. Distribution of clinical stage(FIGO)was as follows: stage Ia, 5 cases(2.8%)stage Ib, 94cases(52.8%)stage Ⅱa, 74cases(41.6%);stage Ⅱb, 5cases(2.8%) 9. The most common size of the cervical lesion was 1-3cm in diameter(44.4%) 10. Among the 178 cases of the invasive carcinoma of the uterine cervix 41 patients (23.2%)received postoperative adjuvant pelvic radiotherapy 11. The incidence of lymph node metastasis was 21.6% in stage Ⅰ and 27.8%in stage Ⅱ. The overall incidence of regional lymph node metastasis was 24.1% 12. 19 cases of ovarian transposition were performed in the women who were aged 24-38 years. Among them, 18cases of right ovary and 1 cases of left ovary were transposed 13. The frequent coexistent diseases in 178 cases with invasinve carcinoma of uterine cervix were myoma uteri(13.1%), anemia (10.2%) adenomyosia(8.7%)hypertension (8.0%)and diabetes mellitus(7.2%) 14. The mean time for radical surgery was 4.7horus 15. The mean bolld transfusion in radical surgery was 5.7 pints of blood(whole blood and packed RBC) 16 Mean time for removal of hemovac was 10.7days after radical hystrectomy in the patients with the invasive carcinoma of the uterine cervix(rang 4-31) 17. Duration of hospital stay after radical hystrectomy ranged 9-68days. The mean was 17.3days 18. The results of survival rate in confirmed patients by follow up at OPD were as follows; a)The 5-year survival rate was 100% in stage Ⅰa, 88.6% in stage Ⅰb, 86.2% in stage Ⅱa, and 50%in stage Ⅱb. The overall 5-year survival rate was 87.2% b)The 5-year survival rate was 75.0% for positive pelvic lymph node metastasis versus 93.2% for negative pelvic lymph node metastasis 19. Out of total 178 patients, 15developed recurrence (8.4%). The sites of recurrence were vaginal stump (40.0%), pelvic cavity (36.4%)and distant metastasis(27.2%) 20. Postoperative complications were observed in 67patents (37.6%)undergoing radical surgery for cervical cancer and 46patient sof them had urologic complications 15 cases of urinary tract infection 19 of functional vesical disturbance 6 of acute renal failure, 5 of vesicovaginal fistula, 1 of ureteral fistula, 12of lymphedma of lower limbs, and 5 cases of lymphocyst were found.

산전 초음파로 진단된 태변성 복막염

진규섭(KS Jin),신진옥(JO Shin),추민호(MH Chu),정재돈(JD Jung),장미경(MK Chang),이선경(SK Lee) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.6

Meconium peritonitis is a chemical or foreign body reaction of the peritoneum resulted from the prenatal small bowel perforation associated with or without obstructive lesions and malformation. Extravasation of sterile meconium into the peritoneal cavity causes an intense peritoneal reaction resulting in characteristic calcification and ascites which might be observed by the prenatal ultrasonographic examination. Prenatal ultrasonographic detection of the meconium preitonitis allows the preparation for the proper management which should reduce the mortality and morbidity of the neonates. Recently, a case of prenatal meconium peritionitis diagnosed by ultrasonography at 38 gestational age weeks was experienced at our department. We represent this case with a brief review of literatures concerned.

고령초산모의 임신예후에 관한 고찰사

김성금(SG Kim),박치희(CH Park),이미영(MY Lee),이경희(KH Lee),장미경(MK Chang),홍희선(HS Hong) 대한산부인과학회 1994 Obstetrics & Gynecology Science Vol.37 No.10

This is a retrospective study of the outcome in pregnancy of more than 20 weeks maturity in a group of 225 primiparas aged 35 years or above who were matched with a control group of 450 primiparas aged less than 35 years old. Seventeen variables of clinical significance were analyzed in order to compare those of 35 years of age and more with those under 35. There were significantly increased rates of cesarean section (51.2%) and gestational diabetes(4.0%) in the older group. The older group also had significantly poorer neonatal outcomes. However, the incidence of elderly primiparas is increasing. Therefore we recommend it is wiser to manage all elderly primiparas as at high risk dealing with each case individually within this framework.

수술적 치료를 받은 자궁경부암 환자에서 CD44v6의 예후인자로서의 가치

방남철(NC Bang),이선경(SK Lee),이상욱(SW Lee),장미경(MK Chang),김승보(SB Kim) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.7

Objective Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumors and the expression of specific CD44 isoforms [splice variants ] has been shown to be associated with metastasis and poor prognosis in human malignancies. Our purpose was to evaluate CD44v6 as prognostic factor. Method We used exon sequence-specific murine monoclonal antibodies to epitopes encoded by exon v6 of human variant CD44 to study the expression of CD44 splice variant by immunohistochemistry in human cervical cancer. Fifty nine patients with surgically treated carcinomas of the cervix stage IB to IIB were included in the study. Result CD44 splice variant CD44v6 was detected in 71.2% [42/59]. Tumors expressing exonv6 had significantly more often involved in lymphovascular space [56.7 vs 82.8%, p = 0.03]. The larger tumors, the higher expression rate of exon v6 [59.4 vs 85.2%, p = 0.03]. Patients suffering from tumors expressing splice variant CD44v6 showed poorer overall survival [p = 0.04]. In case with negative pelvic lymph nodes, we found a poorer prognosis when tumors expressed CD44v6, but statistically not significant [p = 0.10]. Conclusion CD44v6 expression is a poor prognostic factor of cervical cancer stage IB to IIB and can be a indicator of adjuvant treatment in surgically treated uterine cervical cancer patient without pelvic lymph node.

무월경 14 주에 동반된 속발성복강임신 1 예

김준영(JY Kim),박원곤(WG Park),이형근(HG Lee),장미경(MK Chang),박정근(JK Park) 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.7

Abdominal pregnancy is very rare and potentially life-threatening variation of ectopic pregnancy. Early diagnosis is very difficult. In the last several decades prenatal care has improved and noninvasive procedures such as ultrasound scanning and fetal cardiotocography have led to us a better assessment of fetal and maternal disorders. In the last 30 years an increase of diagnosed ectopic pregnancies has been noted and attributed to the greater frequency of pelvic inflammatory disease. Although the incidence of ectopic pregnancy is rising, the incidence of abdominal pregnancy, which is primarily a sequel of a missed ruptured ectopic pregnancy, remains low. We presented a case of secondary abdominal pregnancy in 14 wks with its review of literature.

골반경수술 583 예에 대한 고찰

김준영(JY Kim),강승철(SC Kang),윤병목(BM Yoon),이형근(HG Lee),박원곤(WG Park),장미경(MK Chang),박정근(JK Park) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.10

Five hundred eighty three cases of pelviscopic operation were performed at Kwang-Hye General Hospital from September 1993 to December 1997. The common indications were ectopic pregnancy (33%), myoma uteri (32%), ovarian cyst (21%) and types of surgery were salpingectomy (28%), Classical Intrafascial S.E.M.M Hysterectomy (CISH) and Laparoscopic Assisted Vaginal Hysterectomy (LAVH) (27%), salpingo-oophorectomy (17%), oophorectomy (8%) and ovarian cystectomy (8%). The age of the patients ranged from 21 to 55 years and the mean age was 37.6 years and mean parity of the patients was 1.66 and mean duration of postoperative hospitalization was 3.77 days. The operation time was varied from 30 minutes to 7 hours, mean time of CISH 112.34 minutes, ectopic pregnancy 67.45 minutes, ovarian cyst 69.37 minutes, but recently it was shorter than previously. In our conclusion, pelviscopic surgery makes minimal incision, minimal postoperative adhesion, and low morbidity , and early recovery brings short hospitalization, and reduction of medical cost. Pelviscopic surgery is effective and useful method of treatment in the community hospital.

백서의 난소와 난관에 있어서 CA 125항원의 분포에 관한 연구

김원회,김창훈,장미경,차문석 대한산부인과학회 1990 Obstetrics & Gynecology Science Vol.33 No.2

저자는 백서의 난소와 난관에 있어서 CA 125의 조직내분포를 알아보고자 포르말린에 고정된 후 파라핀에 포매된 표본들의 연속절편을 제작하여 biotin-streptoavidin(B-SA)법에 의한 immunoperoxidase 방법으로 염색하여 다음과 같은 성적을 얻었다. 1. 여러 성숙단계의 난자에 있어서 원시생식세포, 성장난포, 성숙난포, 황체 중 황체가 가장 높은 양성율과 염색도를 보였으며, 대체적으로 성숙단계가 높을수록 양성율과 염색도가 높았다. 2. CA 125항원의 시야별 양성율은 난소의 표면상피에서 평균 98.0%, 난관 상피세포에서 평균 90.3%, 난관의 내윤상근에서 평균 85.8%, 난소 간질세포에서 평균 86.5%, 난관 간질에서 평균 82.9%이었다. 3. HSCORE로 본 염색도는 난소의 표면상피에서 가장 높아 93.0이었고, 난관 상피세포에서 86.2이었으며, 난소 간질세포에서 66.2, 난관 간질에서 45.6, 난관 내윤상근에서 43.1이었다. 4. CA 125의 분포는 난관의 표면상피의 일부에서 세포 첨부 및 첨부막에 있었던 것을 제외하고는 대체적으로 세포질내에 다량 존재하였으나 난소 간질세포에서는 주로 세포내과립양상으로 존재하였다. The OC 125 monoclonal antibody was used to localize CA 125 antigen in formalin-fixed, paraffin-embedded tissue sections of ovary and oviduct of the rate by means of biotin-streptoavidin-immunoperoxidase technic. The results of this study were as follows: 1. The percentage of positivity and degree of staining among various developmental stages of ovum. Generally the higher the maturation stage of ovum, the higher the percentage of positivity and the degree of staining. 2. The percentage of positivity of CA 125 was 98.0 % in the germinal epithelium of ovary, 90.3 % in the lining epithelium of oviduct, 85.8 % in the inner circular muscle of oviduct, 84.5 % in the stroma of ovary, and 82.9 % in the stroma of oviduct. 3. The degree of staining viewed as HSCORE was highest as 93.0 in the germinal epithelium of ovary, 86.2 in the lining epithelium of oviduct, 66.2 in the stroma of ovary, 45.6 in the stroma of oviduct, and 43.1 in the inner circular muscle of oviduct. 4. The pattern of distribution of CA 125 antigen was mostly intracytoplasmic, except intracellular granule pattern in the stroma of ovary.