증례 : 혈액종양 ; AML1-ETO 양성인 양표현형 급성 백혈병의 1예

서주희 ( Ju Hee Seo ),이혜원 ( Hye Won Lee ),임주은 ( Ju Eun Lim ),정주원 ( Joo Won Chung ),최종락 ( Jong Rak Choi ),양우익 ( Woo Ick Yang ),민유홍 ( Yoo Hong Min ) 대한내과학회 2009 대한내과학회지 Vol.76 No.5

BAL은 일반적으로 기타 급성 백혈병보다 예후가 나쁘다고 알려져 있으나, 그 치료방침이 아직 확립되어 있지 않다. AML1-ETO 유전자 재배열은 BAL에서도 좋은 예후인자 중 하나로 제시된 적이 있으며 본 증례에서도 1차례의 관해 유도요법 후 완전관해를 보였고, t(8:21) 즉, AML1-ETO 정량검사상 전사 정도가 현저히 감소함을 경험하였다. 특히, AML에 준한 치료만으로 성공적 관해가 유도되었으며, 이는 BAL에 있어서도 AML1-ETO 종양단백이 병태생리에 주 역할을 할 것임을 짐작할 수 있다. AML에서와 마찬가지로 AML1-ETO 유전자 재배열은 향후 BAL 환자의 치료 효과와 예후를 알 수 있는 지표로 사용될 수 있을 것이다. Biphenotypic acute leukemia (BAL) is a subtype of acute leukemia that expresses two different immunophenotypic lineages, most commonly myeloid and either B- or T-lymphoid lineages. This entity has been defined by a scoring system proposed by the European Group for the Immunological Characterization of Leukemias (EGIL). The prognosis of BAL is regarded as being worse than either acute lymphoid or myeloid leukemia that does not show lineage ambiguity. However, a treatment strategy for BAL has not yet been established. We experienced a case of BAL with the t(8;21) translocation, a favorable cytogenetic rearrangement in acute myeloid leukemia (AML). The patient was successfully treated with cytarabine and anthracycline for induction and consolidation. The quantitative value of the AML1-ETO gene decreased after achieving complete hematologic remission. Thus, the AML1-ETO gene rearrangement in BAL may be associated with an acceptable response to the treatment strategy for AML. (Korean J Med 76:617-621, 2009)

Hyper IgM Syndrome 환자에서 얻은 림프절 및 말초혈액 B세포의 특성

김동수,신경미,양우익,신전수,송창화,조은경,Kim, Dong Soo,Shin, Kyuong Mi,Yang, Woo Ick,Shin, Jeon-Soo,Song, Chang Hwa,Jo, Eun Kyeong 대한소아청소년과학회 2003 Clinical and Experimental Pediatrics (CEP) Vol.46 No.2

목 적 : Hyper IgM syndrome(HIGM)은 크게 세 부류로 나누는데, CD40L 분자의 돌연변이로 초래되며 X-linked로 유전되는 형태를 HIGM1이라고 하고, 상염색체성 열성 형태로 유전되면서 CD40L는 정상적으로 표현되는 형태로 activation-induced cytidine deaminase(AID) 유전자에 이상 때문에 오는 경우를 HIGM2로 분류하고 있다. 다른 한 부류는 X-linked HIGM 증후군의 매우 드문 한 형태로서 발한 저하성 외배엽 이형성증이 동반된 경우로, 이 질환은 전사인자인 nuclear factor ${\kappa}B$의 활성화에 관여하는 nuclear factor ${\kappa}B$ essential modulator를 coding하는 유전자의 돌연변이 때문에 오는 것으로 알려져 있다. 연구자들은 HIGM2와 유사하지만 AID 유전자에 변이는 없는 새로운 형태의 HIGM 환자의 말초 B세포를 이용하여 병인을 조사하고자 본 연구를 시도하였다. 방 법 : 환자의 말초혈액 단핵구를 분리하고, EBV로 immortalization을 시켜 Cycle TEST PLUS DNA Reagent kit를 이용하여 cell cycle을 분석하였다. 환자의 말초혈액 T 세포에서 CD40L의 표현을 immunostaining으로 알아보고, RNA를 추출하여 RT-PCR을 하고 direct sequencing을 통하여 CD40L 유전자의 돌연변이 부위를 찾아보았다. 아울러 AID 유전자의 돌연변이를 찾기 위하여 같은 방법으로 sequencing하고 조사하였다. 환자의 림프절을 병리학적인 검사를 시행하고 CD3, CD23, CD40, Fas-L, bcl-2, BAX의 표현을 알아보기 위하여 immunostaining을 실시하였다. 결 과: 림프절의 광학적 소견은 반응성 여포증식의 소견을 보였으며, 여포와 단구양 증식은 B-세포 표시인자인 L26에 양성을 보였고, 대부분의 형질세포는 IgM에 양성을 보였다. 여포는 CD40, Fas, BAX에 양성반응을 보이고, bcl-2와 Fas-L에 음성반응을 보였다. 말초혈액 B 림프구를 이용하여 cell cycle을 분석한 결과 정상(17.9%)에 비하여 G2/mitosis phase(M3 in figure)가 현저하게 감소(8.5%)되어 있는 양상을 보여주고 있으며, IL-4로 자극한 경우에는 정상인에서 보여주는 양상으로 회복되는 양상을 볼 수 있었다. 단핵수에서 CD40L의 표현은 정상이었고 CD40L 유전자에도 돌연변이는 발견할 수 없었으며, HuAID 유전자에도 돌연변이를 발견할 수 없었다. 결 론 : 환자의 말초혈액 B림프구를 통한 연구 결과, 기존에 보고 되어진 HIGM2 형태와 임상적으로는 비슷하지만, 정상적인 AID유전자를 보이고, G2/mitosis phase가 정상에 비하여 감소된, 새로운 형태의 HIGM이라고 여겨진다. Purpose : Hyper IgM syndrome(HIGM) is characterized by severe recurrent bacterial infections with decreased serum levels of IgG, IgA, and IgE but elevated IgM levels. Recently, it has been classified into three groups; HIGM1, HIGM2 and a rare form of HIGM. HIGM1 is a X-linked form of HIGM and has now been identified as a T-cell deficiency in which mutations occur in the gene that encodes the CD40 ligand molecule. HIGM2 is an autosomal recessive form of HIGM. Molecular studies have shown that the mutation of HIGM2 is in the gene that encodes activation-induced cytidine deaminase(AID). Recently, another rare form of X-linked HIGM syndrome associated with hypohydrotic ectodermal dysplasia has been identified. We encountered a patient with a varient form of HIGM2. To clarify the cause of this form of HIGM, we evaluated the peripheral B cells of this patient. Methods : The lymphocytes of the patient were prepared from peripheral blood. B cells were immortalized with the infection of EBV. Cell cycle analysis was done with the immortalized B cells of the patient. Peripheral mononuclear cells were stained with monoclonal anti-CD40L antibody. Total RNA was extracted from the peripheral mononuclear cells. After RT-PCR, direct sequencing for CD40L gene and HuAID gene were done. Immunostainings of a lymph node for CD3, CD23, CD40, Fas-L, bcl-2, BAX were done. Results : The peripheral B cells of this patient showed normal expression of CD40L molecule and normal sequencing of CD40L gene, and also normal sequencing of AID gene. Interestingly, the peripheral B cells of this patient showed a decreased population of G2/mitosis phase in cell cycles which recovered to normal with the stimulation of IL-4. Conclusion : We suspect that the cause of increased serum IgM in this patient may be from a decrease of G2/mitosis phase of the peripheral B cells, which may be from the decreased production or secretion of IL-4. Therefore, this may be a new form of HIGM.

인간의 정상 자궁내막조직에서의 BCL-2와 BAX 단백질의 발현

홍순옥,이병석,양우익,이지성,차동현,조용선,김정연,박기현,조동제,송찬호,Hong, Soon-Oak,Lee, Byung-Seok,Yang, Woo-Ick,Lee, Jee-Sung,Cha, Dong-Hyon,Cho, Yong-Seon,Kim, Jeong-Yeon,Park, Ki-Hyun,Cho, Dong-Jae,Song, Chan-Ho 대한생식의학회 2000 Clinical and Experimental Reproductive Medicine Vol.27 No.3

Objective: To investigate the distribution of BCL-2, BAX proteins and DNA fragmented cells in the normal human endometrium during at each menstrual cycle in order to find out whether apoptosis regulates cyclic endometrial change. Methods: Normal endometrial tissues were obtained from 40 patients, $32{\sim}45$ year of age, all with regular menstrual cycle, who were undergoing abdominal hysterectomy for myoma of uterus or cervical intraepithelial neoplasia for the period from 1992 through 1997. Immunohistochemical staining was used to determine the expression of BCL-2 and BAX protein with paraffin-embedded tissues. Results: BCL-2 was expressed on the glandular epithelial cells and stromal cells during the proliferative phase. The intensity of BCL-2 was increased predominantly on the basal layer than the functional layer in late proliferative phase. However, BCL-2 immunoreactivity was decreased in the secretory phase. BAX was expressed predominantly during the secretory phase. The intesity was increased in late secretory phase rather than early secretory phase. DNA fragmented cells were detected in a few cells at each phase. However, it was increased during the late secretory phase. Conclusion: Apoptosis-related genes, BCL-2 and BAX, may play a role in the regulation of cyclic endometrial change.

사지에 발생한 지방육종

이수현,조인제,양우익,서진석,신규호,Lee, Soo-Hyun,Cho, In-Je,Yang, Woo-Ick,Suh, Jin-Suck,Shin, Kyoo-Ho 대한근골격종양학회 2010 대한골관절종양학회지 Vol.16 No.2

목적: 사지에 발생한 지방육종의 치료 결과와 임상적 예후 인자에 대해 알아보고자 하였다. 대상 및 방법: 1994년 4월부터 2005년 12월까지 본원에서 사지에서 발생한 원발성 지방육종으로 진단받고 치료받은 44명 중 5년 이상 추시 관찰이 가능하였던 40명을 대상으로 후향적 분석을 시행하였다. 이 중 13명은 수술 후 방사선 치료를 함께 시행 받았다. 국소 재발과 원격 전이 및 5년 무병생존율을 조사하였고, 나이, 성별, 종양의 크기, 비계획적 절제술 여부, 조직학적 유형, 수술적 절제연, 방사선 치료 병행 유무 등이 5년 무병생존율에 미치는 영향을 분석하였다. 결과: 국소 재발 3예, 원격 전이는 4예가 있었고, 5년 무병생존율은 85.0%였다. 조직학적 유형은 점액성 지방육종이 26예, 고분화 지방육종이 8예, 원형 세포형 지방육종이 4예였으며, 비분화 지방육종, 다형성 지방육종이 각각 한 예였다. 고분화 지방육종, 점액성 지방육종, 원형 세포형 지방육종 세 군의 5년 무병 생존율은 각각 100.0%, 84.6%, 75.0%였다(p=0.419). 수술 절제연에서 종양 세포가 관찰되지 않았던 환자(n=32)에서는 5년 무병 생존율이 90.6%였고, 절제연에서 종양 세포가 관찰된 환자(n=8)에서는 62.5%였다(p=0.003). 결론: 수술적 절제연에서 종양 세포의 관찰 여부가 5년 무병생존율에 유의한 인자였다. Purpose: We analyzed disease free survival and the prognostic factors of liposarcoma in the extremity. Materials and Methods: Between 1994 and 2005, of 44 patients who were diagnosed and treated for liposarcoma of the extremity, 40 patients were restrospectively analysed. 13 out of 40 patients got postoperative radiotherapy. We examined local recurrence, distant metastasis and disease free 5-year survival rate. We also analyzed clinical prognostic factors, such as age, gender, size of tumor, prior unplanned excision, histologic type, surgical excision margin and postoperative radiotherapy respectively. Results: There were 3 cases of local recurrence and 4 cases of distant metastasis. The disease free 5-year survival rate was 85.0%. 26 patients presented with myxoid, 8 well differentiated, 4 round cell, 1 pleomorphic and 1 dedifferentiated histology. The disease free 5-year survival rate of mixoid, well differentiated and round cell liposarcoma were 100.0%, 84.6% and 75.0% (p=0.419). The 5-year disease free survival rate was 90.6% in negative surgical margin (n=25) and 62.5% in positive surgical margin (n=15) (p=0.003). Conclusion: Our study suggests that surgical excision margin is significant prognostic factor for 5-year disease free survival rate.

증식성 근막염의 세침흡인 세포학적 소견

최윤정,이상엽,양우익,정순희,이광길,Choi, Yoon-Jung,Yi, Sang-Yeop,Yang, Woo-Ick,Jung, Soon-Hee,Lee, Kwang-Gil 대한세포병리학회 1993 대한세포병리학회지 Vol.4 No.1

Proliferative fasciitis is a benign pseudosarcomatous mesenchymal lesion occurring in the subcutis. The lesion occurs clinically as a tumorous mass that develops within a rather short time in elderly patients. We recently experiecened a case of fine needle aspiration cytology of proliferative fasciitis in the left anterior chest wall of a 72 year-old male patient. The smear revealed two types of cells. One was the large and mostly oval cell with one or two nuclei lying at the periphery of the cell body and abundant basophilic cytoplasm like the ganglion cell. The nuclei were round to oval, had vesicular chromatin and contained prominent nucleoli. The other was the spindle shaped fibroblast with an oval nucleus. The differential diagnosis includes a true tumor such as ganglioneuroma, rhabdomyosarcoma, and liposarcoma and therefore fine needle aspiration cytology is very much indicated in order to exclude these possibilities.

인간난포에서 Apoptosis 관련 단백질 및 Apoptotic 세포의 면역학적 발현

박성록,이병석,양우익,김종화,박병주,박기현,조동제,송찬호,Park, Sung-Rok,Lee, Byung-Seok,Yang, Woo-Ick,Kim, Jong-Hwa,Park, Byung-Joo,Park, Ki-Hyun,Cho, Dong-Jae,Song, Chan-Ho 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.3

Objective : To investigate the expression of apoptosis related proteins and apoptotic cells on the human ovarian follicles. Materials and Methods: Thirty five Formalin-fixed paraffin-embedded human ovarian tissue blocks were selected from the surgical pathology files of the department of pathology, College of Medicine, Yonsei University, for the period from 1996 to 1998. All specimen were from premenopausal women aged from $32{\sim}45$. Ovarian tissues were collected from the patients performing hysterectomy for benign uterine diseases. Immunohistochemical staining was performed for the detection of DNA fragmented cell, Bcl-2, Bax, Fas and Fas-ligand. Results: Bcl-2 and bax were not expressed on the surrounding cells and oocyte of the primary, primordial and preantral follicles. Fas and Fas-ligand (Fas-L) were not expressed on the surrounding cells on the primordial and primary follicles. But expressed on the surrounding granulosa cells and oocyte in the primordial and primary follicles. In the healthy follicles, Bcl-2 was expressed on the granulosa cells, however, Bax was not expressed. DNA fragmented cells were expressed on the inner granulosa cell layer of atretic follicles. Conclusion: Fas, Fas-ligand, and Bax may be responsible for the follicular atresia and Bcl-2 may be involved in the follicular survival in the human ovary.

한국인에서 D16S539 유전좌의 유전적 다형성

신경진,양윤석,최종훈,양우익,조상호,김종열,Shin, Kyoung-Jin,Yang, Yun-Seok,Choi, Jong-Hoon,Yang, Woo-Ick,Cho, Sang-Ho,Kim, Chong-Youl 대한안면통증구강내과학회 2000 Journal of Oral Medicine and Pain Vol.25 No.4

The D165539 locus was investigated to collect population genetic data in the Korean population. The selected subject was unrelated 293 Korean people. DNA was extracted from the samples and PCR was performed with fluorescent primer. The amplified fragment was analysed by automated DNA sequencer and it's application software. Among the Korean population, 7 allele and 18 geneotype were observed and allele No. 9 is mostly frequent(0.2679) and then allele No. 11(0.2679), allele No. 9(0.2645). The observed heterozygosity and the expected heterozygosity is 0.7466, 0.7829 each. The polymorphism information content(PIC) is 0.7466. The power of discrimination(PD) and the mean exclusion chance(MEC) are calculated to be 0.9190 and 0.5775.

귀밑샘의 기무라병의 세침흡인 세포학적 소견 -세포학적 검사로 예측할 수 없었던 1예 보고-

김세훈,김혜령,김성은,양우익,이광길,홍순원,Kim, Se-Hoon,Kim, Hae-Ryoung,Kim, Sung-Eun,Yang, Woo-Ick,Lee, Kwang-Gil,Hong, Soon-Won 대한세포병리학회 2003 대한세포병리학회지 Vol.14 No.2

Kimura's disease is a chronic inflammatory disorder of unknown cause and is most prevalent among Asians. The cytologic findings of Kimura's disease are significant numbers of eosinophils in a background of lymphoid cells, occasional fragments of collagenous tissue, proliferation oi vessels, and Warthin-Finkeldey polykaryocytes. Among these features, the most important cytologic feature of Kimura's disease is a significant numbers of eosinophils. We experienced a case of Kimura's disease in the parotid gland which we fatted to recognize on cytology due to the apparent paucity of eosinophils. On careful retrograde reviewing of the cytologic findings, a few scattered leukocytes, previously interpreted as polymorphous leukocytes, had bilobed nuclei and coarse green but granular cytoplasm on Papanicolaou preparation. These leukocytes showed obvious orange-red intracyloplasmic granules as in eosionophils on Giemsa stain. The paucity of eosinophils may be due to the thick fibrosis around lymphoid follicles or any technical error during aspiration. Whereas the Warthin-Finkeldey type giant cell is not a sensitive cytologic marker of Kimura's disease, it may be a helpful cytologic feature. To reach a correct cytologic diagnosis of Kimura's disease, It is important to keep in mind that searching for Warthin-Finkeldey type giant cells and evaluation of Giemsa stain for detection of eosinophils would be helpful.

갑상선 종양에서 아포프토시스(Apoptosis)와 세포증식 표지자(Ki-67)의 상관관계 분석

한경희 ( Kyung Hee Han ),양우익 ( Woo Ick Yang ),김선정 ( Sun Jung Kim ),김태전 ( Tai Jeon Kim ) 대한임상검사과학회 2007 대한임상검사과학회지(KJCLS) Vol.39 No.3

To clarify the growth mechanisms of thyroid tumors, we investigated apoptotic cells in 88 thyroid tumors, consisting of 24 adenomas, 58 papillary thyroid carcinomas, and 6 undifferentiated carcinoma, using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate digoxigenin-nick end labeling (TUNEL). The cell proliferating marker was also evaluated immunohistochemically using the monoclonal antibody to Ki-67 antigen (MIB-1) in the same tumors. The apoptosis was expressed as a percentage of the TUNEL-positive cells in the tumor cells, and a proliferating marker, being the percentage of Ki-67 positive cells, was counted up each tumor. The statistical analysis were used analysis of variance (ANOVA) and student``s t-test that were analyze the differences in the rate of each histological types of the thyroid tumors. The overall level of apoptosis was extremely low in all histological types of the thyroid tumors analyzed, the mean apoptosis being 0.31±0.40 in adenoma, 0.55±0.48 in papillary thyroid carcinoma, and 4.60±3.27 in undifferentiated carcinoma. The Ki-67 protein in the thyroid tumor subtypes was significantly lower in adenoma and papillary carcinoma, at 2.45±2.99 and 6.27±4.42, respectively, than that in undifferentiated carcinoma at 26.47±23.88 (p<0.0001). There was no correlation between clinicopathological factors and apoptosis or Ki-67 in papillary thyroid carcinoma. In conclusion, our findings suggest that apoptosis occurs infrequently in thyroid tumor, and that cell proliferating maker Ki-67 markedly differs according to the thyroid tumor subtypes. Moreover, the ratio between proliferating cells and apoptotic cells may reflect thyroid tumor progression.

한국인의 림프종양 구진증과 피부 CD30양성 퇴형성 대형세포 림프종에서 Epstein-Barr 바이러스의 발현 빈도에 관한 연구

김유찬 ( You Chan Kim ),양우익 ( Woo Ick Yang ),이민걸 ( Min Geol Lee ),박상건 ( Sang Gun Park ),김수남 ( Soo Nam Kim ),조광현 ( Kwang Hyun Cho ),이석종 ( Seok Jong Lee ),이미우 ( Mi Woo Lee ),고재경 ( Jai Kyoung Koh ) 대한피부과학회 2005 대한피부과학회지 Vol.43 No.12