일반연제 발표 : 부인종양학 1 ; 자궁경부암에서 CD44v6의 발현양상과 예후와의 상관관계

방남철,이선경,장미경,이주희,김승보 대한산부인과학회 1997 대한산부인과학회 학술대회 Vol.80 No.-

Atypical PAP Smear의 임상적 분석

방남철,김창남,이선경 대한산부인과학회 1995 대한산부인과학회 학술대회 Vol.76 No.-

수술 및 항암화학요법으로 와전관해를 보인 상피성난소암 환자에서 발생한 뇌전이 1 례

허주엽,방남철 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.3

Cerebral metastses secondary to primary epithelial ovarian carcinoma are unusual. The incidence was estimated under 1%, but some authors reported higher incidence than previously reported data. Recently, we experienced a case of cerebral metastasis secondary to primary epithelial ovarian cancer. We present this case with review of brief related literatures.

자궁외임신의 임상적 고찰

이선경,김승보,정순자,변종원,방남철 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.11

The incidence of ectopic pregnancy has been increasing for many years. Ectopic pregnancy is still a leading cause of materal death despite improved diagnosis and therapy. There is still much to be learned about ectopic pregnancy, its etiology, diagnosis and managment. The study was undertaken on 512 patients with pathologically or laparoscoically proven diagnosis of ectopic pregnancies at the KyungHee Medical Center from Jan. 1, 1989 to Dec. 31, 1994. The results of the study were as follows; 1. The incidence of ectopic pregnancy was 1 in twenty deliveries(512/10,752). 2. The most frequent age group was in 25~34 years of ages. 3. The obstetrical histories were abortion in 77.2%, delivery in 64.1%, nulligravida in 35.9% and previous ectopic pregnancy in 7.6%. 4. A previous history of abdominal or pelvic surgery was in 17.2% and tubal sterilization was in 12.7%, pelvic inflammatory disease in 8.4%. 5. The most frequent interval between last menstrual period and the onset of symptoms was 6~8 weeks in 39.5%. 6. On symptomatological analysis, amenorrhea was encountered in 93.0%, lower abdominal pain in 81.2%, and vaginal spotting in 45.5%. 7. The diagnostic positive rate was 100% in β-hCG and laparoscopy, 88.2% in urine hCG test, 84.7% in culdocentesis, and 85.2% in ultrasonogram. 8. The histopathology of endometrium showed decidual reaction(49.2%), secretory phase (27.9%), Arias-Stella reaction(14.7%) and proliferative phase(8.2%). 9. Ectopic gestation was implanted on the fallopian tube in 96.5%, on the ovary in 2.1% and on the cervix in 1.2%, and 1 case was intraabdominal pregnancy. 10. The operative precedures were salpingectomy in 69.1%, salpingo-oophorectomy in 11.7%, cornual resection in 5.1%.

수술적 치료를 받은 자궁경부암 환자에서 CD44v6의 예후인자로서의 가치

이선경,김승보,장미경,이상욱,방남철 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.7

서론 자궁경부암의 선별검사로 인한 이형성의 조기진단이 증가함에 따라 침윤성 자궁경부암의 발생빈도가 감소하고 있지만 아직도 그 치료와 예후의 결정에는 연구해야할 과제가 많이 남아 있다. CD44는 세포막의 당단백 수용체로서 임파구의 귀환작용 및 세포와 세포간 또는 세포와 세포간질간의 상호작용에 관계하며 변형CD44는 주로 종양세포에 존재하여 종양세포가 전이의 성향을 갖게한다고 알려져 있다. 변형CD44는 이미 쥐의 선암세포주나 인간의 유방암 및 대장암에서 예후에 나쁜 영향을 미치는 것으로 나타났으나 부인종양에서는 아직 연구자료가 많지 않은 상태이다. 이에 변형CD44중에서도 자궁경부암의 예후에 가장 밀접한 관련이 있는 것으로 알려진 CD44v6에 대해 예후와의 관계를 밝혀보고자 하였다. 연구방법 CD44v6의 단일클론항체를 이용한 면역조직화학염색으로 경희대학교 부속병원 산부인과에서 수술적치료를 받은 59례의 자궁경부암 환자를 검사하여 그 발현과 예후와의 관계를 알아보았다. 결과 CD44v6의 발현은 종양의 크기가 3cm이상인 군에서 85.2%로 3cm미만인 군의 59.4%보다 높게 나타났으며 임파혈관 침윤이 보이는 경우에서 82.8%로 임파혈관 침윤이 없는 경우의 56.7%보다 높게 나타났다. 5년생존율을 비교하면 CD44v6가 발현된 군에서 59.5%로 비발현 군의 88.2%보다 나쁘게 나타났다. 또한 골반임파절의 전이를 보이 지 않는 자궁경부암 환자에서도 CD44v6발현군이 더욱 낮은 5년 생존율을 보였으나 통계적 유의성을 갖지 못하였다. 결론 이와같은 결과로 향후 이 부분에 대한 더 많은 연구를 통해 골반임파절 전이가 없는 침윤성 자궁경부암의 수술후 치료의 결정에 도움을 줄 수 있으리라 생각된다. 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.

자궁경부암에서 인유두종 바이러스 유형에 따른 p53 유전자변이와 단백발현에 관한 연구

이선경,김승보,이주희,방남철,지성길 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.11

Oncogenic human papillomavirus(HPV) infection has been implicated in the pathogenesis of cervical carcinoma. The HPV E6 and E7 oncoproteins are thought to play a crucial role in this process by their interactions with the p53 protein and the retinoblastoma suceptibility gene products respectively. The E6 protein binds to and stimulates the degradation of the p53 protein and mutations involving evolutionary conserved regions of the p53 gene also can alter p53 fu-nction, so both HPV E6 protein and p53 mutation may play a role in the carcinogenesis of cer-vical carcinoma. The purposes of this study are to examine the role of p53 gene in relation to the presence of HPV DNA in primary cervical carcinoma and to assess the prognostic value of the p53 gene and HPV infection in surgically treated cervical carcinoma. Formalin fixed, paraffin embeded blocks of 73 cervical carcinomas were evaluated for the status of oncogenic HPV infection by in situ hybridization, and the p53 overexpression by immunohistochemical staining. 43 cases out of 73 cervical carcinomas were evaluated for the HPV type by polymerase chain reaction (PCR)-Southern blot analysis, and the presence of mutations involving exon 4-10 of the p53 gene was examined by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP), and then, confirmed by direct DNA sequencing. 48 cases of 73 cervical carcinomas showed oncogenic HPV DNA by in situ hybridization and 22 cases showed p53 overexpression by immuno-histochemical staining. There was inverse correlationship between HPV infection and p53 overexpression(p=0.03). HPV infection and p53 overexpression were not significantly correlated with clinicopathological parameters such as age, FIGO stage, histologic type, tumor size, lymph node metastasis, depth of invasion, and tumor differentiation. 32 cases of 43 cervical carcinomas showed oncogenic HPV DNA by PCR-Southern blot analysis. 30 cases(69.8%) of 43 cervical carcinomas showed HPV 16 DNA and 9 cases(20.9%) showed HPV 18 DNA and 11 cases(25.6%) showed no HPV 16/18 DNA. 8 cases of 43 cervical carcinomas showed p53 gene mutation in PCR-SSCP analysis. 7 cases of 8 mutations showed positive p53 overexpression and another 1 case showed negative p53 overexpression. 4 cases of 8 mutations had no HPV 16/18 infection and another 4 cases had HPV 16 and/or 18 infection. There was no significant correlation between p53 mutation and HPV infection. In 8 cases showing mutation, 4 cases showed point mutation, 3 cases sho- wed frame shift mutation, and another 1 case showed deletion from codon 125 to 132. p53 mutations were located at exon 4, 5, 6, 7, and 8, highly conserved region. Oncogenic HPV DNA can be identified in most cervical carcinomas, and mutations involving highly conserved regions of p53 gene, although infrequent in cervical cancer, occur preferentially in tumors without HPV infection but indenpendently. Although HPV infection and p53 overexpression shows no prognostic values in our study, further investigation is required for clarifyng its prognostic value in gynecologic malignancies.