Gynecologic Oncology : New developing biomarkers in cervical cancer

김병기 ( Byoung Gie Kim ) 대한산부인과학회 2009 서울심포지움 Vol.14 No.-

최우수눈문상 : 한국여성암연구재단상

김병기 ( Byoung Gie Kim ),Chel Hun Choi,Jeong Won Lee,Tae Joong Kim,Woo Young Kim,Hee Rim Nam,Seung Jae Huh,Je Ho Lee,Duk Soo Bae 대한산부인과학회 2008 대한산부인과학회 학술대회 Vol.94 No.-

Adenoid cystic carcinoma of Bartholin`s gland: A review of the literature and report of a patient

김병기 ( Byoung Gie Kim ),( Kyoung Lan Jung ),( Jeong Won Lee ),( Sun Joo Lee ),( Chang Soo Park ),( Je Ho Lee ),( Geung Hwan Ahn ),( Seong Jae Hur ),( Jae Chul Sim ),( Duk Soo Bae ) 대한산부인과학회 2003 대한산부인과학회 학술대회 Vol.89 No.-

자궁경부 상피내종양 및 자궁경부암 조직에서 bcl-2 및 c-myc 암유전자 발현과 세포증식 및 apoptosis와의 상관관계에 관한 연구

김병기(Byoung Gie Kim),이효표(Hyo Pyo Lee) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.8

bcl-2 암유전자는 여러 가지 자극에 의한 apoptosis를 차단함으로써 유전자 이상을 가진 세포가 계속 생존하면서 유전자 변이가 누적되는 결과를 초래한다고 알려져 있다. 한편 c-myc 암유전자는 세포증식과 apoptosis를 유도하는 이중적 기능을 가지고 있으며 생존 신호가 결여될 경우에는 오히려 세포의 apoptosis를 유발한다고 알려져 있다. 그러나 c-myc과 bcl-2가 동시에 발현되면 bcl-2는 c-myc의 세포증식 작용은 영향을 주지 않고 apoptosis만을 선택적으로 차단함으로써 유전자 변이 세포의 생존 뿐만 아니라 증식을 촉진하는 것으로 관찰되었다. 자궁경부암에서 c-myc과 bcl-2 발현에 관한 개별적 보고는 있었으나 이들 두 유전자의 동시발현 및 이들 유전자들이 실제 암조직상에서 세포증식 및 apoptosis에 어떠한 영향을 미치는가에 관한 연구는 보고된 것이 없다. 따라서 본 연구에서는 자궁경부암 발생 과정중에서 bcl-2 및 c-myc 발현과 세포증식, apoptosis와의 상관관계를 알아보고자 하였다. 본 연구에서는 10개의 정상 자궁경부조직, 30개의 자궁경부 상피내종양 조직, 20개의 자궁경부암조직에서 bcl-2와 c-myc에 대한 면역조직화학 검사를 시행하였으며 세포증식과 apoptosis는 각각 Ki-67 면역조직화학적 방법과 TUNEL 방법으로 확인하였다. 또한 환자의 임상병리학적 인자들과의 상관관계도 알아보았다. 정상 자궁경부, 자궁경부 상피내종양, 자궁경부암조직 중 자궁경부암조직에서만 bcl-2와 c-myc 단백이 각각 35%와 50%에서 관찰되었으며, 또한 bcl-2와 c-myc의 동시발현이 25%에서 관찰되었다. 세포증식 지수(상피세포 100개중 Ki-67양성 세포수)는 정상 자궁경부, 상피내종양, 자궁경부암으로 진행되면서 10.2, 24.1, 59.7, 71.2로 유의하게 증가하는 양상을 보였으며(p<0.01), apoptosis 지수(상피세포 100개중 apoptosis 세포수)도 0, 0.33, 1.85, 3.89로 점차 증가하는 양상을 보였다(p<0.01). 또한 세포증식 지수와 apoptosis 지수와는 높은 상관관계(r=0.7451, p=0.0002)를 나타내었다. 그러나 자궁경부암 조직중 bcl-2 발현군과 비발현군간에 apoptosis지수에는 차이가 없었으며(p=0.4765), c-myc 발현군과 비발현군간에도 세포증식 지수에는 차이가 없었다(p=0.6891). 또한 bcl-2와 c-myc의 동시 발현군과 나머지 군간에도 증식지수와 apoptosis 지수에 차이가 없었다(각각 p=0.6311 및 p=0.7600). 한편 bcl-2와 c-myc의 동시 발현과 잘 알려져 있는 자궁경부암의 임상병리학적 예후인자들(종양 크기, FIGO 임상병기, 림프절 전이등)과는 유의한 상관관계가 없었다. 이상과 같은 결과에서 자궁경부암발생 과정에서 세포증식과 apoptosis는 병변의 등급과 비례하여 증가하고 apoptosis는 세포증식과 관련된 변화로 사료되었다. 한편 bcl-2와 c-myc과 발현은 자궁경부암에서만 관찰되는 유전자 변이로서 자궁경부 상피내종양의 발생과 진행과정에는 영향을 미치지 않으며, 또한 자궁경부암 조직에서도 암조직 전체의 세포증식 및 apoptosis와는 관련이 없을 것으로 사료되었다. bcl-2 prevents cell death from a wide variety of stimuli and provides survival of cells with accumulated genetic alterations and c-myc can promote both cell proliferation and cell death through the transcriptional regulation of target genes. Although several studies have been reported on the expression of bcl-2 or c-myc separately, little has been known about the role of coexpression of bcl-2 and c-myc to cell proliferation and apoptosis, as well as the frequency of these coexpression in cervical cancer specimens. In this study, we have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia(CIN) to determine the role of coexpression of bcl-2 and c-myc during progression into cervical cancer. Proteins and transcripts of bcl-2 and c-myc were evaluated by immunohistochemistry in 60 clinical specimens(20 cervical cancer, 30 CIN, and 10 normal cervix). In addtion, we evaluated kinetic indices of cell proliferation and apoptosis simultaneously. The cell proliferation index was determined by detection of the Ki- 67 in immunohistochemistry. Apoptotic index was determined by the detection of apoptotic cells with TUNEL staining. Medical records including pathologic reports were reviewed. Overexpression of bcl-2 and c-myc was identified in 7(35%) and 10(50%) of 20 cervical cancer specimens respectively, but none in normal cervix and CIN samples. In addition, coexpression of bcl-2 and c-myc was found in 5(25%) of 20 cervical cancer specimens. The cell proliferation index increased with progression from normal to CIN and invasive cancer(normal cervix, 10.2; CIN 1, 24.1; CIN 2/3 59.7; cervical cancer, 71.2; p <0.01). The apoptotic index also increased with grade of lesions(normal cervix, 0; CIN 1, 0.33; CIN 2/3, 1.85; cervical cancer, 3.89; p <0.01) and showed a significant correlation with proliferation index(r=0.7451, p=0.0002). However, there was no significant difference in apoptotic index between bcl-2 positive and bcl-2 negative group in cervical cancer(p=0.4765). In addition, there was also no significant difference in cell proliferation between c-myc positive and c-myc negative group(p=0.6891). Furthermore, there was no significant difference in cell proliferation and apoptosis between bcl-2 and c-myc positive group and others in cervical cancer(p=0.6311 and p=0.7600 respectively). The well-known clinicopathologic parameters, including tumor diameter, FIGO clinical stage, lymph node metastasis, did not correlate with simultanuos positive immunoreactivity for bcl-2 and c-myc proteins in cervical cancer. In conclusion, the cell proliferation and apoptosis increase with increasing lesion grade of cervical neoplasia and apoptosis correlates with cell proliferation. In addition, overexpression of bcl-2 and/or c-myc may be genetic alteration found only in cervical cancer and may not play a role in the development and progression of CIN. However, neither bcl-2 nor c-myc immunoreactivity correlated with the proliferation index or apoptotic index. These results suggest that other factors may also play a role in controlling the cell proliferation and apoptosis of cervical cancer.

초기 자궁내막암 환자에서의 복강경유도하 질식 자궁절제술과 복식 자궁절제술에 대한 비교 연구

김민규 ( Min Kyu Kim ),최동석 ( Dong Seok Choi ),김우영 ( Woo Young Kim ),최철훈 ( Chel Hun Choi ),김태중 ( Tae Joong Kim ),이정원 ( Jeong Won Lee ),김병기 ( Byoung Gie Kim ),이제호 ( Je Ho Lee ),배덕수 ( Duk Soo Bae ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.12

목적: 초기 자궁내막암의 수술적치료 시 복강경유도하 질식 자궁절제술 및 골반림프절절제술군과 복식수술군의 수술결과 및 재발율에 대해 비교하고자하였다. 연구 방법: 2003년 3월부터 2005년 5월까지 초기 자궁내막암 환자를 인구학적 특성이 같은 63명을 선택하여 복강경유도하 질식 자궁절제술 및 골반림프절절제술군 26명, 복식수술군 37명으로 나누어 수술 전후 혈색소 차이, 평균수술시간, 취득한 골반림프절갯수, 평균재원일수, 추가치료율, 재발률을 비교하였다. 결과: 복강경유도하 질식 자궁절제술 및 골반림프절절제술을 시행한 군과 복식수술을 시행한 군과의 비교에서 수술 전후 혈색소 차이, 평균수술시간, 취득한 골반림프절 갯수, 평균재원일수, 재발률에 통계적으로 유의한 차이가 없었다. 결론: 초기 자궁내막암의 수술 시 복강경유도하 질식자궁절제술 및 골반림프절절제술 방법이 복식방법에 비해 수술결과 및 재발률에 통계적으로 유의한 차이가 없으며 그 대체 수술법으로 많은 활용이 기대되었다. Objective: To compare laparoscopic surgery with conventional abdominal surgery in patients with early stage endometrial cancer. Methods: A retrospective review of 63 patients with early stage endometrial cancer managed between March 2003 and May 2005. Two groups were defined whether they had been treated by laparoscopy (case group: n=26) or by laparotomy (control group: n=37). We compared age, body mass index (BMI), hemoglobin change, operation time, number of pelvic lymph nodes, hospital stay, case with adjuvant treatment and recurrence between two groups. Results: There was no statistical difference in characteristics (age, BMI, nulliparity, previous abdominal surgery, FIGO stage, histologic grade). between case and control group. In addition, there was no statistical difference in operation data and outcomes between two groups. Hemoglobin changes were 1.1 g/dL (case group) vs 1.7 g/dL (control group) (p=0.072). Operation time was 131 min vs. 115 min. The numbers of lymph nodes obtained were 8.7 vs 7.7 (right) 9.2 vs. 7.6 (left). Hospital stays were 8.4 vs. 9.2 days. Adjuvant treatment cases were 7 vs. 15. Recurrent case was one in each group. Two patients initially evaluated by laparoscopy were converted to laparotomy due to bleeding and adhesion. Conclusion: Laparoscopic surgery for treatment of early endometrial cancer is a safe and effective alternative to laparotomy . However, long-term survival and risk of recurrence have yet to be determined.

원발성 악성 광인대 종양

김하정 ( Ha Jeong Kim ),김민재 ( Min Jae Kim ),이은주 ( Eun Joo Lee ),최철훈 ( Chel Hun Choi ),김태중 ( Tae Joong Kim ),이정원 ( Jeong Won Lee ),김병기 ( Byoung Gie Kim ),성창옥 ( Chang Ok Seong ),배덕수 ( Duk Soo Bae ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.7

Primary broad ligament tumors are a rare entity, although secondary involvement of broad ligament by a malignancy arising elsewhrere in the abdomen/pelvis is common. Among the primary broad ligament tumors, leiomyoma is the most frequent histopathological type followed by serous papillary cystadenoma of borderline malignancy. Primary sarcomas and high-grade carcinomas have been extremely rarely reported. Because of the rarity of disease, its treatment policy, follow-up strategy and prognosis are yet to be established and it is managed as an ovarian malignancy. We had experienced a case of clear cell adenocarcinoma arising from broad ligament and report this case with a brief review of literature.

성경험이 없는 22세 여성 자궁경부에서 발생한 투명세포암

김철중 ( Chul Jung Kim ),박창수 ( Chang Soo Park ),이정원 ( Jeong Won Lee ),이수호 ( Su Ho Lee ),이선주 ( Sun Joo Lee ),김병기 ( Byoung Gie Kim ),이제호 ( Je Ho Lee ),배덕수 ( Duk Soo Bae ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.7

자궁경부에 발생한 점액표피양암종 증례보고

김서희 ( Seo Hee Kim ),김하정 ( Ha Jeong Kim ),이정원 ( Jeong Won Lee ),김병기 ( Byoung Gie Kim ),배덕수 ( Duk Soo Bae ) 대한산부인과학회 2012 Obstetrics & Gynecology Science Vol.55 No.10

Primary mucoepidermoid carcinoma (MEC) is a very uncommon tumor in uterine cervix. Most has been introduced in the salivary gland, but this tumor can arise from other organs. Primary MEC in the cervix is morphologically similar to that of the salivary gland. We experienced one case of primary cervical MEC of 44-year-old women. The cancerous mass was found in the anterior lip of the cervix without any extension. The radical hysterectomy, right salpingoophorectomy and pelvic lymphadenectomy by laparoscopic method were performed. On pathologic reports, tumor was suggested to be MEC of the cervix, International Federation of Gynecology and Obstetrics stage IB1 without risk factors. We had decided to observe closely without adjuvant therapy. But multiple metastases including local and distant sites were noted 4 months after the primary surgery. We decided to start concurrent chemoradiation with paclitaxel-carboplatin. But she expired after 19 months of primary surgical treatment. We report this case with the brief review.

상피성 난소암에서 수술후 일차 항암화학요법으로 시행된 Paclitaxel - Cisplatin 의 효용성에 대한 연구

김상희(Sang Hee Kim),송용중(Yong Jung Song),이향(Hyang Lee),이삼미(Sam Mi Lee),최석철(Suck Chul Choi),유상영(Sang Young Ryu),김병기(Byoung Gie Kim),박상윤(Sang Yoon Park),이경희(Kyung Hee Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.12

N/A Objective : The purpose of this retrospective study is to assess the efficacy and toxicity of paclitaxel/cisplatin as first-line chemotherapy after cytoreductive surgery in patients with epithelial ovarian cancer. Material & Methods : From November 1999 to April 2001, 31 patients with histologically-proven epithelial ovarian cancer not previously treated with chemotherapy entered the study. FIGO stage IA or IB and grade 1 or 2 tumors were excluded. A comprehensive staging was performed during initial laparotomy. Paclitaxel was administered at a dose of 135 mg/m2, intravenously with cisplatin (75 mg/m2) every 3 weeks for 6 planned cycles, with prophylactic oral dexamethasone regimen (20 mg b.I.d.). The response of patients was evaluated with tumor markers and CT before and after chemotherapy. Responses and toxicities were defined according to the Gynecologic Oncology Group (GOG) criteria. Results : The overall response rates were 73% (16/22) in patients with residual disease after cytoreductive surgery (complete response, 64%; partial response, 9%). The median survival was 18 months. Grade 3/4 neutropenia and neuropathy (grade 2) were observed in 16 (52%), 12 (39%) patients, respectively. Conclusion : The combination of paclitaxel and cisplatin is a well tolerated regimen with significant activity in the treatment of epithelial ovarian carcinoma after surgery.

침윤성 자궁경부암 환자의 임상적 양상 및 예후에 관한 연구

김법종(Beob Jong Kim),이재규(Lee Jae Kyu),이주헌(Joo Heon Lee),유상영(Sang Young Ryu),김종훈(Jong Hoon Kim),김병기(Byoung Gie Kim),박상윤(Sang Yoon Park),이의돈(Eui Don Lee),이경희(Kyung Hee Lee) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.9

목적: 침윤성 자궁경부암은 우리 나라 여성에서 가장 높은 발생 빈도를 보이는 질환으로 그 동안 국내 자궁경부암 환자의 예후에 관한 여러 연구에도 불구하고 생존 여부의 조사에 있어서의 어려움으로 신뢰할만한 자료가 거의 없는 실정이므로, 이 연구를 통하여 임상적 양상과 실제 5년 생존율을 알아보고자 하였다. 연구방법: 연구 대상은 1992년 1월부터 12월까지 1년간 본 원자력병원 산부인과에서 침윤성 자궁경부암으로 진단 및 치료를 시행한 489명의 환자를 대상으로 하였다. 환자들의 의무기록을 통하여 연령, FIGO 임상 병기, 조직학적 양상, 림프절 전이, 치료 방법 등 임상적 양상을 확인하였으며, 환자의 생존 여부는 행정전산망 및 경찰의 전산망, 통계청의 조사자료 등을 통하여 확인하였다. 결과: 환자의 연령별 분포는 51세에서 60세 사이가 32.7%로 가장 많았으며, FIGO 임상 병기는 IIb기가 32.5%로 가장 높은 빈도를 보였다. 임상병기 Ib기 및 IIa기의 치료방법은 수술적 치료가 주로 시행되었으며(65%), 이 이상의 병기에서는 방사선 치료가 주로 시행되었다(97%). 림프절의 전이는 Ib기 6%, IIa기 29% IIb기 36%로 IIb기 이상에서 높은 빈도를 보였다. 실측 5년 생존율은 72.2%였고 병기에 따른 생존율은 Ia기 100%, Ib기 94%, IIa기 82%, IIb기 63% IIIa기 36%, IIIb기 47%, IV기 0%였다. 임파절 전이여부에 따른 5년 생존율은 수술적으로 임파선 전이여부를 확인한 Ib-II기 환자에서 임파선 전이가 없는 군이 91.9%인데 비해 전이가 수술적으로 확인된 군은 73.1%를 보였다. 5년 생존율에 영향을 미치는 예후 인자는 FIGO 임상 병기와 림프절의 전이였으며, 연령 및 조직학적 유형은 통계학적 의의를 확인할 수 없었다. 결론: 1992년 1월부터 12월까지 1년간 본 원자력병원 산부인과에서 침윤성 자궁경부암으로 진단 및 치료를 받은 489명 환자의 실측 5년 생존율은 72.2% 였고, 5년 생존율에 영향을 미치는 예후인자는 FIGO 임상병기와 림프절의 전이였다. Objectives: This non-randomized retrospective study was to investigate the clinical characteristics and to evaluate the actual 5-year survival rate of the patients with invasive cancer of the cervix. Methods: 489 evaluable patients with invasive cancer of the cervix were treated at Korea Cancer Center Hospital from January to December 1992. In this retrospective study, we studied the clinico-pathologic characteristics(age, FIGO stage, histologic type, nodal metastasis) and treatment modalities by the review of medical records. Especially, the survival was confirmed by the support of the police and government office. Results: The most common subsets of patients were found in the group of FIGO stage IIb(32.5%) and age between 51 and 60(33%). Surgery was the main treatment in stage Ib/IIa(65%) and radiation in stage IIb or more(97%). Nodal metastasis were surgically identified in 6% of stage Ib, 29% of stage IIa and 36% of stage IIb. Overall actual 5-year survival rate was 72.2%; stage Ia(100%), Ib(94%), IIa(82%), IIb(63%), IIIa(36%), IIIb(47%), and IV(0%). The five-year survival rate according to LN status in surgically confirmed FIGO stage Ib-II patients were 91.9% in negative patients and 73.1% in positive patients respectively. Five-year survival rate was significantly different according to stage(P < 0.02) and nodal metastasis(p < 0.01). However, age and histologic type did not show any significant differences in survival. Conclusion: Overall actual five-year survival rate of 489 evaluable patients with invasive cancer of the cervix who were treated at Korea Cancer Center Hospital from January to December 1992 was 72.2%. Five-year survival rate was different according to stage and nodal metastasis.