대장 선종 및 대장 선암에서 TGF-β1, 제2형 TGF-β 수용체 및 VEGF 단백의 면역조직화학적 발현
Expression of TGF-β1, TGF-β Receptor Type II and VEGF in Colorectal Adenomas and Adenocarcinomas
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
목적: 내시경 또는 외과수술로 절제된 대장 선종과 대장 선암 조직을 대상으로 면역조직화학 염색을 시행하여 TGF-β1, TGF-βRII 및 VEGF의 발현정도를 비교 관찰함으로써 TGF-β1, TGF-βRII 및 VEGF이 대장 선암의 발생 과정 및 진행에 관련이 있는지를 알아보고자 하였다. 대상 및 방법: 대장 선종 조직 20예와 대장 선암 40예를 대상으로 tissue microarray를 제작하여 TGF-β1, TGF-βRII 및 VEGF에 대한 면역조직화학 염색을 시행하였다. 결과: 대장 선종군에서 TGF-β1, TGF-βRII 및 VEGF의 염색강도는 고이형성군에서 증가하였으며 TGFβRII의 염색강도는 고이형성군에서 유의하게 높았다(p=0.021). 대장 선암군에서 TGF-β1, TGF-βRII 및 VEGF의 발현 및 염색강도는 선종군과 비교하여 유의하게 높았으나(p<0.001), 염색강도와 나이, 성별, 종괴의 크기, 병기 및 분화도 사이에 유의한 연관성은 없었다. 결론: 대장 선암에서 TGF-β1, TGFβRII 및 VEGF의 염색강도의 증가는 이들 단백이 대장 선암의 형성과정 및 진행에 중요한 역할을 한다는 것을 시사한다. TGF-β의 세포 성장 억제기능의 소실은 대장암의 발암과정 중 비교적 초기에 일어나는 것으로 생각한다.
Abstract
Background/Aims: The aim of study was to investigate the expression of TGF-β, TGF-RII and VEGF determined by immunohistochemical analysis with a comparison of the clinicopathological parameters such as tumor size, grade of dysplasia, lymph node metastasis and Dukes' stage in colorectal adenomas and adenocarcinomas, by use of a tissue microarray method. Methods: The expression of TGF-β1, TGF-βRII, and VEGF was determined by immunohistochemistry in 20 adenomas and 40 adenocarcinomas. Tissue microarrays consisting of 2 mm cores from corresponding blocks were constructed and stained. Results: In adenomas, the staining intensity of TGF-β, TGF-βRII and VEGF was increased in a high-grade dysplasia group of patients as compared a with low-grade dysplasia group of patients, respectively. The staining intensity of TGF-βRII was significantly increased in a high-grade dysplasia group of patients than a low-grade dysplasia group of patients (p =0.021). For the adenocarcinomas, the expression and staining intensity of TGF-β1, TGF-βRII and VEGF were increased as compared with the adenomas (p<0.001). However, no significant correlation was observed between the staining intensity of TGF-β, TGF-βRII and VEGF and the clinicopathological parameters. Conclusions: The increased expression of TGF-β1, TGF-βRII and VEGF in colorectal adenocarcinoma suggests a role for these proteins in colorectal carcinogenesis. Loss of the growth-inhibitory effect of TGF-β may commence in the early stage of colorectal carcinogenesis. (Korean J Gastrointest Endosc 2007;35:313-320)
참고문헌 (33)
- "The evolution of cancer of the colon and rectum", pp.2251~2270
- "Role of transforming growth factor beta in human disease", 342, pp.1350~1358 (2000)
- "Mechanism of activation of the TGF-β receptor", attisa(l), pp.341~347
- "TGF-β receptor-mediated signalling through Smad2, Smad3 and Smad4", 16, pp.5353~5362 (1997)
- "Regulation of immune responses by TGF-β", 16, pp.137~161 (1998)
- "Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease", pp.693~699
- "Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β", 18, pp.1280~1291 (1999)
- "Transforming growth factor β and cancer", 21, pp.367~403 (1995)
- "Transforming growth factor-β: vasculogenesis, angiogenesis, and vessel wall integrity", 8, pp.21~43 (1997)
- "Defective haematopoiesis and vasculogenesis in transforming growth factor-β1 knock out mice", 121, pp.1845~1854 (1995)
- "TGF-β receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis", 179, pp.297~302 (1996)
- "Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy", 1, pp.1623~1634 (1995)
- "of transforming growth factor-β1 in invasion and metastasis in gastric carcinoma", 17, pp.607~614 (1999)
- "Vascular endothelial growth factor and the regulation of angiogenesis", 55, pp.15~35 (2000)
- "novel method for immunohistochemical antibody testing", pp.244~248
- "Tissue microarrays for high-throughput molecular profiling of tumor specimens", 4, pp.844~847 (1998)
- "Tissue array method for large scale clinicopathologic study", 36, pp.199~204 (2002)
- "The cell biology of transforming growth factor β", pp.79~87
- "Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-β", 71, pp.165~207 (1997)
- "Inhibition of hepatocyte DNA synthesis by transforming growth factor-β1 and cyclic AMP effect immediately before the G1", S border, 3598~3603
- "Disruption of the antiproliferative TGF-β signaling pathways in human pancreatic cancer cells", 17, pp.1969~1978 (1998)
- "Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers", 59, pp.320~324 (1999)
- "Altered expression of transforming growth factor-β ligands and receptors in primary and recurrent ovarian carcinoma", 85, pp.658~668 (1999)
- "Down-regulation of TGF-beta receptors in human colorectal cancer: implications for cancer development", 80, pp.194~205 (1999)
- "Expression of transforming growth factor β receptors in normal human colon and sporadic adenocarcinomas", 114, pp.1211~1220 (1998)
- "TGF β1 expression and angiogenesis in colorectal cancer tissue", 8, pp.496~498 (2002)
- "The expression of transforming growth factor-1 and its signaling receptors in human colorectal carcinoma", 35, pp.115~122 (2001)
- "Expression of p53, pRB, and p16 in lung tumours: a validation study on tissue microarrays", 200, pp.610~619 (2003)
- "Multiple tissue core arrays in histopathology research: a validation study", 192, pp.549~553 (2000)
- "Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors", 158, pp.1245~1251 (2001)
- "Angiogenesis and its role in colorectal tumor and metastasis formation", 31(6), pp.3S~9S (2004)
- "Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer", 55, pp.3964~3968 (1995)
- "Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma", 78, pp.226~231 (1996)
