난소종양환자에서 종양표지자의 진단적 가치

신광식(Kwang Sik Shin),김석모(Seok Mo KIm),최호선(Ho Sun Choi),변지수(Ji Soo Byun) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.4

Objective: This study was designed to evaluate the efficiency of tumor markers level for early diagnosis of ovarian malignancy and for differentiation between benign and malignant ovarian tumors. Materials and Methods: We determined preoperative serum tumor markers level in patients who were going to have an operation due to ovarian tumor in OB & GY Dept. of Chonnam University Hospital from April 1993 to September 1999. Results: 1) The average values of serum tumor markers in patients with malingnant ovarian tumors were statistically higher than those of benign ovarian tumors. among malignant ovarian tumors, positive rate of all serum tumor markers was highest in epithelial ovarian carcinoma group. and among ovarian tumor markers, and positive rate of CA 125 was highest in epithelial ovarian carcinoma. 2) Dermoid cyst and endometioma were correlated to CA 19-9, CA 125 levels respectively. for malignant tumors, mucinous ovarian adenocarcinoma and non-mucinous ovarian adenocarcinoma were CA 19-9, CA 125 levels respectively. 3) Among ovarian tumor markers, CA 125 was the most in sensitivity and CA 72-4 was the most in specificity and diagnostic efficiency. 4) For postmenopausal women with ovarian tumors, elevated levels of at least one of the 4 tumor markers were present in the serum in 85.7% of the women who developed cancer, 62.5% of women with borderline, 27.8% of women with benign ovarian tumors. Conclusion; It is suggested that determination of serum tumor markers in patient suspected of ovarian tumor may be helpful to clinician for early diagnosis, differentiation between malignant and benign ovarian tumors.

종양표지자 발굴의 동향과 기대

권순일 ( Sun-il Kwon ) 한국고등직업교육학회 2013 한국고등직업교육학회논문집 Vol.14 No.2

Tumor markers are the biological substances produced by cancer cells or by other types of cells of the body due to cancer with high specificity. Tumor markers can be detected with the blood, tumor tissue, stool, urine or other bodily fluids of cancer patients. The usage of tumor markers may be diagnosis of cancer, prediction of a patient’s therapeutic response to certain drugs, determination of cancer recurrence, and so on. Discovery and development of new tumor marker is of much concern because of its great potential in cancer management as well as its application in target therapy. The candidates for tumor markers could be obtained from DNA, RNA, hormones, glycoproteins, metabolites, tumor-associated antigens, enzymes, or oncogene products. To discover new tumor markers, a holistic and systematic high-throughput process called omics technology is commonly adopted. Among the omics like genomics, transcriptomics, proteomics, and metabolomics, the proteomic approach is most widely used due to the diversity and dynamism of proteins in relation to cancer biology. In this short review, the latest research trend and prospective in the discovery and development of new tumor markers was discussed.

Evaluation of the UniCelTM DxI 800 Immunoassay Analyzer in Measuring Five Tumor Markers

박윤희,김현숙,박용정,박정용 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.3

Purpose: Tumor marker concentrations in a given specimen measured by different analyzers vary according to assay methods, epitopes for antibodies used, and reagent specificities. Although great effort in quality assessment has been instituted, discrepancies among results from different analyzers are still present. We evaluated the assay performance of the UniCelTM DxI 800 automated analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers. Materials and Methods: The linearity and precision performance of the five tumor marker assays were evaluated, and concentrations of the respective markers as measured by DxI were compared to those measured by other conventional analyzers (ADVIA CentaurTM and VitrosTM ECi) using 200 specimens collected from 100 healthy persons and 100 patients with respective cancers. Results: The linear fits for all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for all). The imprecision of each tumor marker assay was less than 5% coefficient of variation, except for low and high concentrations of AFP. The results from UniCelTM DxI 800 were highly correlated with those from other analyzers. Conclusion: Our results demonstrate that UniCelTM DxI 800 has good linearity and precision performance for the tumor markers assayed in this study. However, there were discrepancies between assaying methods. Efforts to standardize tumor marker assays should be undertaken,and the redetermination of cut-off levels is necessary when developing methods of analyzing tumor markers.

자궁경부 편평상피암 환자에서 종양표지물질 SCC 및 CEA와 말초혈 임파구의 임상적 의의

김옥화(OH Kim),배석년(SN Bae),백남규(NG Baik),변철(C Byun),주수만(SM Joo),손우석(WS Shon),김승조(SJ Kim),남궁성은(SE Namkoong) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.2

To evaluate the significance of tumor markers, SCC and CEA, which seems to be represent the part of biological characteristics of tumor, and peripheral lymphocytes which seems to be represent the part of host immune defense mechanisms in patients with cervical cancer, We studied 67patients with squamous cell carcinoma of the uterine cervix (stage IB+IIB) who were admitted to Kangnam St. Mary`s Hospital, Department of Obstetrics and Gynecology, Catholic University Medical Colloerge from January 1991 to December 1992. The first venous blood sample for Tumor markers determinations and peripheral lymphocytes counts was taken befor therapy and following samples were obtained after radiotherapy or radical surgery. Firth-three patients had Cis-platinum based neoadjuvant combination chemotherapy and clinical responses to chemotherapy were evaluated by colposcopy and vaginal sonogram. Serum SCC level of 2.0 ng/ml, CEA level of 2.5 ng/ml were determined as cut-off levels. The results were as follows: 1. In 67 patients with squamous cell carcinoma of uterine cervix, the pretreatment positive rate of SCC and CEA was 28.4% and 29.9% respectively and the positive rate of either one of CEA and SCC was 44.8% (30/67). 2. The pretreatment positive rates of either one of CEA and SCC were significantly increased by clinical stage. 3. The 44-months disease free survival rate for patients with postive tumor marker was 69.3% versus 90.7% for patients with negative marker. 4. The 36-months disease free survival rate for patients with positive to both tumor marker was 44.4% and it was significantly lower than 80.4% of positive for either one or 90.7% of negative for both 5. The 37-months disease free survival rate for stage IB patients with positive for either one of both tumor markers was 90% versus 100% for patients with negative tumor marker and 45-months disease free survival rate was 43.6% versus 74.0% for stage IIB patients . But it was not statistically significant. 6. There was no direct coreelation between positive rate of tumor marker and clinical response to chemoheraphy. 7. The peripheral lymphocyte counts coldn`t affect the clinical response rate to the chemotherapy and prognosis. There results indicate that concomitat measurement of SCC and CEA may be more useful in determining prognosis than measurement of one tumor maker alone and pre- and post treatment peripheral lymphocyte counts couldn`t affect the prognosis of patients with stage IB to IIB of squamouse cell carcinoma of uterine cervix.

폐암의 표지자로써 Cyfra 21-1의 유용성

박현덕,정현식,박정식,임성호,이은정,윤중원,정수석,신호철,이승세 대한내과학회 2002 대한내과학회지 Vol.62 No.4

Background : Cytokeratins are epithelial markers whose expressions are not lost during malignant transformation. The utility of cytokeratin fragment (Cyfra) 21-1, a new tumor marker, was investigated in 110 patients with lung cancer. The aims of this study were to confirm sensitivity of Cyfra 21-1 in detecting non-small cell cancer, to assess the potential relationship between Cyfra 21-1 and disease stage of the lung cancer. Methods : We measured serum levels of four tumor marker (NSE, CEA, SCC Ag, Cyfra 21-1) in 110 patients with lung cancer. The measurement of serum level of Cyfra 21-1 was performed with a cut off value of 3.3 ng/mL. An immunoradiometric assay was used to detect a fragment of the cytokeratin 19. The patients were grouped according to the stage of the disease and tumor type. Results : Overall sensitivity of Cyfra 21-1 was relatively high (51.8%) than others tumor markers. Sensitivity of this marker was especially high for adenocarcinoma (63.2%) and squamous cell carcinoma (54.1%). In contrast, sensitiviy of Cyfra 21-1 was relatively low for small cell lung carcinoma (40.0%). Serum levels of Cyfra 21-1 were higher in advanced nonsmall cell lung cancer than early stage disease. Conclusion : We conclude that Cyfra 21-1 is a sensitive tumor marker of nonsmall cell lung cancer, especially adenocarcinoma and also may be a useful adjunctive marker for disease monitoring.(Korean J Med 62:415-421, 2002) 목적 : 폐암에 대한 종양표지자로서는 암태아성 항원 (CEA), 편평세포암 항원 (SCC Ag), 신경원 특이성 에놀라제 (NSE) 등이 있으나 Cyfra 21-1은 최근에 발견된 종양표지자로서 비소세포성 폐암에 민감도가 우수한 것으로 보고되고 있다. 본 연구에서는 폐암에서 Cyfra 21-1의 민감도를 알아보고 폐암의 병기와의 관계를 알아 보았다. 대상과 방법 : 환자는 강북삼성병원에 입원하여 조직학적 및 세포병리검사상 확진된 폐암환자 110명을 대상으로 연구하였고 환자의 혈청에서 CEA, SCC Ag, NSE, Cyfra 21-1을 측정하였다. 결과 : 전체 폐암 환자에서 종양표지자의 민감도는 Cyfra 21-1이 51.8%였다. Cyfra 21-1의 양성율은 선암에서 63.2%, 편평세포암에서 54.1%, 소세포암에서 40.0%였고, 소세포암에 비해 선암과 편평세포암에서 통계학적으로 유의하게 (p<0.05) 높게 측정되었다. 병기에 따른 Cyfra 21-1의 민감도는 다른 종양표지자보다 양성율이 높고 T 병기가 진행하면서 높아지는 경향이 있었지만 통계적인 유의성은 없었고 림프절의 전이와 타장기로의 전이 유무에 따른 Cyfra 21-1의 양성율도 통계적으로 유의한 차이는 없었다. 선암과 편평세포암에서 병기에 따른 Cyfra 21-1의 평균치는 병소의 크기가 증가함에 따라 증가하지만 통계적인 유의성이 없었고 림프절 침범과 타장기로의 전이 유무에 따른 Cyfra 21-1의 농도의 변화도 통계적으로 유의한 차이는 없었다.

의생물학 문헌에 보고된 후보 암표지자 정보추출시스템 개발

채정민,오흥범,최성은,차충환,정순영,김명희 대한진단검사의학회 2008 Annals of Laboratory Medicine Vol.28 No.1

Background : Since the human genome project was completed in 2003, there have been numerous reports on cancer and related markers. This study was aimed to develop a system to extract automatically information regarding the relationship between cancer and tumor markers from biomedical literatures. Methods : Named entities of tumor markers were recognized by both a dictionary-based method and machine learning technology of the support vector machine. Named entities of cancers were recognized by the MeSH dictionary. Results : Relational and filtering keywords were selected after annotating 160 abstracts from PubMed. Relational information was extracted only when one of the relational keywords was in an appropriate position along the parse tree of a sentence with both tumor marker and disease entities. The performance of the system developed in this study was evaluated with another set of 77 abstracts. With the relational and filtering keyword used in the system, precision was 94.38% and recall was 66.14%, while without the expert knowledge precision was 49.16% and recall was 69.29%. Conclusions : We developed a system that can extract relational information between a tumor and its markers by incorporating expert knowledge into the system. The system exploiting expert knowledge would serve as a reference when developing another information extraction system in various medical fields. (Korean J Lab Med 2008;28:79-87)

동계 마우스 종양의 방사선 감수성 예측인자로서의 생물학적 표지자

장세경(Sei Kyung Chang),성진실(Jinsil Seong),김성희(Sung Hee Kim),신현수(Hyun Soo Shin) 대한방사선종양학회 2006 Radiation Oncology Journal Vol.24 No.2

목 적: 방사선 감수성이 다양한 동계(syngeneic) 마우스 종양들을 대상으로 50% 종양억제선량과 종양성장지연 등 방사선 감수성을 대변하는 지표와 방사선에 의해 유도되는 아포토시스 간에 상관관계가 있는지 여부를 알아보고자 하였다. 또한 아포토시스와 관련된 여러 유전물질의 기본(constitutive) 발현수준을 측정한 후 이들 상호 간의 상관관계를 분석하여 방사선 감수성을 예측할 수 있는 생물학적 표지자를 알아보고자 하였다. 대상 및 방법: 동계 마우스 종양으로는 난소암 OCa-I, 유방암 MCa-K, 편평상피세포암 SCC-VII, 섬유육종 FSa-II, 간암 HCa-I을 사용하였고 이들은 PCR-SSCP 검사상 p53이 모두 자연형인 종양들이었고 주령 8∼10 주인 C3H/HeJ 웅성 마우스를 사용하였다. 50% 종양억제선량과 종양성장지연 및 방사선에 의해 유도되는 아포토시스를 측정하여 이들과 방사선에 의해 유도되는 아포토시스간의 상관관계를 분석하여 방사선에 의해 유도되는 아포토시스로 방사선 감수성을 예측할 수 있는지 여부를 알아보고, 또한 아포토시스와 관련된 유전물질 p53, p21WAF1/CIP1, BAX, Bcl-2, Bcl-xL, Bcl-xs, p34 등의 기본 발현양상 및 발현수준을 Western blot과 농도계측기로 측정한 후 이들 상호 간의 상관관계를 분석하였다. 결 과: 방사선에 의해 유도된 아포토시스의 정도와 종양성장지연과의 사이에는 통계적으로 유의한 상관관계가 존재하였다(R=0.922, p=0.026). 50% 종양억제선량과의 사이에는 통계적 유의성은 변연수준이었으나(p=0.070) 상관관계의 경향을 보였다(R=-0.848). p21WAF1/CIP1과 p34의 기본 발현수준과 50% 종양억제선량(R=0.893, p=0.041와 R=0.904, p=0.035) 및 종양성장지연(R=-0.922, p=0.026와 R=-0.890, p=0.043) 사이에는 통계적으로 유의한 상관관계가 존재하였다. 즉, p21WAF1/CIP1과 p34의 기본 발현수준이 낮은 경우에 방사선 감수성이 높고, 기본 발현수준이 높은 경우에는 방사선 감수성이 낮은 상관관계가 존재함을 알 수 있었다. 결 론: 방사선에 의해 유도된 아포토시스의 정도로 종양의 방사선 감수성을 예측하여 볼 수 있을 것으로 생각하며, 종양의 방사선 감수성을 예측할 수 있는 생물학적 표지자로 p21WAF1/CIP1와 p34의 기본 발현수준이 이용될 수 있을 것으로 생각한다. Purpose: We investigated whether a relationship exists between tumor control dose 50 (TCD50) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD50, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8∼12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD50, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21WAF1/CIP1, BAX, Bcl-2, Bcl-xL, Bcl-xs, and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD50 or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD50, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with TCD50 (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21WAF1/CIP1 and p34 showed a significant correlation either with TCD50 (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890, p=0.043). The tumors with high constitutive expression levels of p21WAF1/CIP1 or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of p21WAF1/CIP1 or p34 can be used as biological markers which predict the radiosensitivity.

Nogo‐A expression in oligodendroglial tumors

Jung, Tae‐,Young,Jung, Shin,Lee, Kyung‐,Hwa,Cao, Van Thang,Jin, Shu‐,Guang,Moon, Kyung‐,Sub,Kim, In‐,Young,Kang, Sam‐,Suk,Kim, Hyung‐,Seok,Lee, Min‐,Che Blackwell Publishing Asia 2011 Neuropathology Vol.31 No.1

<P>Nogo‐A belongs to the reticulon protein family and is expressed in the inner and outer loops of myelin sheaths of oligodendrocytes. We analyzed the patterns of Nogo‐A expression in human gliomas in an effort to identify a useful marker for the characterization of oligodendroglial tumors. We determined the expression of Nogo‐A in a panel of 58 astrocytic and oligodendroglial tumors using immunohistochemistry and compared the expression of Nogo‐A with Olig‐2, a recently identified marker for oligodendrogliomas. To localize Nogo‐A expression, immunofluorescent staining was performed using other glial markers (MAP‐2 and GFAP). We also confirmed the overexpression of the Nogo‐A protein in 53 astrocytic and oligodendroglial tumors using Western blot analysis. Based on immunohistochemical analysis, Nogo‐A and Olig‐2 had specificity in the detection of oligodendroglial tumors from astrocytic tumors (<I>P</I> = 0.001). The level of Nogo‐A staining was highly correlated with Olig‐2 (<I>P</I> = 0.001). The sensitivity and specificity of Nogo‐A for oligodendroglial tumors was 86.9% and 57.1%, respectively. Nogo‐A expression overlapped that of other oligodendroglial markers, but with different patterns of expression. Western blot analysis revealed that Nogo‐A is predominantly expressed in 85.7% of oligodendroglioma cells and 93.7% of anaplastic oligodendroglioma cells. Like other oligodendroglial markers, Nogo‐A is highly expressed in oligodendroglial tumors; however, it does not serve as a definite marker specific for oligodendroglial tumors.</P>

송과체 부위 종양 20례에 대한 임상 분석

홍성조,신형식,이민성,문재곤,김윤모 대한신경외과학회 1993 Journal of Korean neurosurgical society Vol.22 No.8

A retrospective analysis was made of 20 patients with pineal region tumors who were treated at the Department of Neurosurgery, Capital Armed Forces General Hospital between May of 1987 and March of 1990. We performed ventriculo-peritoneal shunt in 17 patients with obstructive hydrocephalus. Tissue diagnosis was obtained in 7 patients before irradiation and 13 patients underwent irradiation without histological diagnosis. Among 7 biopsy-proven cases, 5 were germinoma, one was mixed germ cell tumor and another one was astrocytoma. The response to irradiation and tumor marker study revealed that 13 patients who did not have tissue diagnosis seemed to be germinomatous non-germinomatous germ cell tumors and endodermal sinus tumor. So, the following results were obtained. 1) The patients were all young males. 2) The main presenting symptoms and signs were headache, vomiting and papilledema. 3) The tumors were mainly presented as a round well-enhancing masses with calcification. 4) Based on the classification of pineal tumor, germinoma was predominant tumor type. 5) The extrapineal metastasis was found in 5 cases(25.0%). 6) The tumor marker (α-FP or HCG) was positive in 5 cases(25.0%). 7) Germinoma showed excellent prognosis after the irradiation.

Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer

Stephen Chee Liang Koh,Chan Yiong Huak,Delfi Lutan,Johny Marpuang,Suwiyoga Ketut,Nyoma Gede Budiana,Agustria Zainu Saleh,Mohamad Farid Aziz,Hariyono Winarto,Heru Pradjatmo,Nguyen Khac Han Hoan,Pham Vi 대한부인종양학회 2012 Journal of Gynecologic Oncology Vol.23 No.3

Objective: To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. Methods: Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. Results: The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). Conclusion: The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors. Objective: To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. Methods: Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. Results: The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). Conclusion: The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.