KR0100984

KCCH/RR-045/2000

A Study on Activation of FDG-PET Use

GLUT- 1S| Expression

The FDG Uptake and GLUT-1 Expression of the Mediastinal Nodes in the Non-Small Cell Lung

IV ^Hl^ FDG ^41^ Glucose Transporter(GLUT-l)^ Expression''^] ^

2000. 12. 31.

: % 5)

•1- fi

I. FDG Glucose Transporter (GLUT-1) Expression n.

FDG ^^1- Glucose Transporter^ FDG o.s FDG-PET

m. S.x4.$\ FDG ^i FDG-PET1-

anti-Glut-1 antibodyS immunohistostaining*l-^4. H^ 317](mm), ^^ follicle ^^ KGrade 1-4), ^5.^ follicle^ 'g^ ^^(1-4),

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PET FDG

-2- SUMMARY

1. Project Title The FDG uptake and glucose transporter(GLUT-l) expression of the mediastinal nodes in the non-small cell lung cancer

2. Objective and Importance of the Project FDG-PET scan provides physiologic and metabolic information that characterizes lesions that are indeterminate by CT and that accurately stages the distribution of lung cancer. Many authors reported that mediastinal staging of non-small-cell lung cancer was improved markedly by FDG-PET in addition to CT, but the problem of false positive and negative N2 was not overcome completely. The aim of this study was. to understand the mechanism of FDG uptake in the mediastinal nodes, and improve the accuracy of mediastinal staging of non-small cell lung cancer by PET.

3. Scope and Contents of the Project To evaluate factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was done in 20 LSCLC patients. The GLUT-1 expression was studied by of paraffin section from the mediastinal nodes(n=50, true positive 11, true negative 23, false positive 11, false negative 5) using the antiGLUT-1 . The staining intensity of tumoKgrade 0-4), percentage of tumor, level of follicular hyperplasia(grade 1-4), and staining intensity of follicle was also studied.

4. Results and Proposal for Applications The staining intensity of true positive nodes was higher than that of false negative group(Mann-Whitney test, P=0.07) in the metastased nodes. The level of follicular hyperplasia of false positive nodes was higher than that of true negative nodes in non-metastased nodes(P=0.02). This finding indicates that FN interpretation of mediastinal nodes by FDG-PET might be associated with low uptake of FDG due to low expression of GLUT-1, and that FP might be associated with high level of follicular hyperplasia as a reactive change to inflammatory and/or immune reaction.

-3- CONTENTS

1. Chapter 1. Introduction

2. Chapter 2. Materials and Methods

3. Chapter 3. Results

4. Chapter 4. Discussion

5. Chapter 5. Conclusion

6. Chapter 6. References

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1. Pauwels EKJ, Ribeiro MJ, et al. FDG Accumulation and tumor biology. Nucl Med Biol 1998:25:317-322 2. Merrall NW, Plevin R, Gould GW. Growth factors, mitogens, oncogens and the regulation of glucose transport. Cell Signal. 1993:5:667-675 3. Yamamoto T, Fukumoto H, et al. Overexpress of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun. 1990:170:223-230 4. Brown RS, Wahl RL. Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer. 1993:72:2979-2985 5. Brown RS, Leung JY, Kison PV, et al. Glucose transporters and FDG uutake in untreated primary human non-small cell lung cancer. J Nucl Med. 1999:40:556-565 6. Younes M, Brown RW, Stevenson R, et al. Overexpression of Glut-1 and Glut-3 in stage I nonsmall cell lung cancer is associated with poor survival. Cancer 1997:80:1046-51 7. Scott WJ, Schwabe JL, Gupta NC, et al. Positron emission tomography of lung and mediastinal lymph nodes using 18-F fluorodeoxyglucose. Radiology 1993:188:487-90 8. Sasaki M, Ichyya Y, Kuwabara Y, et al. The usefulness of FDG positron emission tomography for the detection of mediastinal metastases in patients with non-small cell lung cancer: a comparative study with X-ray computed tomography. Eur J Nucl Med 1996:23:741-47 9. Valk PE, Pounds TR, Hopkins DM, et al. Staging non-small cell lung cancer by whole body positron emission tomographic imaging. Ann Thorac Surg 1995:60:1573-82 10. Scott WJ, Gobar LS, Terry JD, et al. Mediastinal lymph node staging of non-small cell lung cancer: a prospective comparison of computed tomography and positron emission tomography. J Thorac Cardiovasc Surg 1996:11:642-8 11. **S\^, ^S., 33J-&, «g#J?-, %^, &AQ. «l;Ml5.sfl£ %x\$\ ^ ^ H^ 3 61 #3# WFDG-PET^ ol-g-. tfl^JjLi*]4^3*1 199932:910-5 12. Steinert HC, Hauser M, Allemann E, et al. Non-small cell lung cancer: Nodal staging with FDG PET versus CT with corerelative. lymph node mapping and sampling. Radiology 1997:202:441-6 13. Harber RS, Rathan A, Weiser KR, et al. Glut-1 glucose transporter expression in colorectal carcinoma. Cancer 1998:83:34-40 14. Higashi T, Tamaki N, Torizuka T, et al. FDG uptake, Glut-1 glucose transporter and cellularity in human pancreatic tumors. J Nucl Med

-15- 1998:39:1727-1735 15. Reisser C, Eichhorn K, et al. Expression of facilitative proteins during development of squamous ceil carcinomas of head and neck. Int J Cancer 1999:80:194-198 16. Noguchi Y, Saito MD, et al. Expression of facilitative glucose transporter in gastric tumors, hepatogastroenterology 1999:46:2683-9 17. Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997:111:1718-23 18. Nathwani BN, Winberg CD, Diamond LW, et al. Morphologic ' criteria of follicular from florid reactive follicular hyperplasia-' a study of 80 cases. Cancer 1981:48:1794-1806 19. Weiss LM, Strickler JG, Medeiros LJ, et al. Proliferative rates of non-Hodgkins' as assessed by Ki-67 antibody. Hum Pathol 1987:18:1155-1159

-16- BIBLIOGRAPHIC INFORMATION SHEET

Performing Org. Sponsoring Org Standard Report INIS Subject Rppnrt Nr> Rppnrt Nr>. No. C.ndp KCCH/RR-045/2000 The FDG uptake and glucose transporter(GLUT-l) expression of Title/Subtitle the mediastinal nodes in the non-small cell lung cancer

Project Manager and Dept. HeeJong, BAIK, Dept. of Thoracic Surgery

Researcher and Dept Jin Haeng, Jung, Dept. of

Seoul, Korea Cancer Center Pub. Pub. Place Rep. of Pub. Org. Hospital Date Korea Page Fig. Table Yes( 0 ), No( ) Size A4

Note

Classified Open( 0 ), Outside( ), Class Report Type Research

Sponsoring Org. Contract No.

Abstract

The aim of this study was to understand the mechanism of FDG uptake in the mediastinal nodes, and improve the accuracy of mediastinal staging of non-small cell lung cancer by PET. To evaluate factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was done in 20 LSCLC patients. The GLUT-1 expression was studied by immunohistochemistry of paraffin section from the mediastinal nodes(n=50, true positive 11, true negative 23, false positive 11, false negative 5) using the antiGLUT-1 antibody. The staining intensity of tumor(grade 0-4), percentage of tumor, level of follicular hyperplasia(grade 1-4), and staining intensity of follicle was also studied. The staining intensity of true positive nodes was higher than that of false negative group(Mann-Whitney test, P=0.07) in the metastased nodes. The level of follicular hyperplasia of false positive nodes was higher than that of true negative nodes in non-metastased nodes(P=0.02). This finding indicates that FN interpretation of mediastinal nodes by FDG-PET might be associated with low uptake of FDG due to low expression of GLUT-1, and that FP might be associated with high level of follicular hyperplasia as a reactive change to inflammatory and/or immune reaction. Subject Keywords

Transportpr ?! FDP, PRT 3 T.nng Canrpr 4 MpHiastinal Staging IMS

KCCH/RR-045/2000

H^£] FDG ^#15}- Glucose Transporter (GLUT- Expression

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