GLUT- 1S| Expression
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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 Cancer 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), IV. Al PET # ^• test, P=0.07). *>fl^fe- PET ^ ^H^^ follicle leveH °1 ^^fe FDG Hl^r GLUT- iHS^S. ^1-afl FDG ^ follicular hyperplasia^ V. FDG ^ -ffe FDG-PET^l 6.4 FDG GLUT-1 l- fe GLUT-1 ^^) FDG ^ 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 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 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 -4- A tfl-g- -5- all 1 S- M ^(Glucose- transporter, GLUTW ^^^^(Positron emission tomography, PET) fluorine-18 deoxyglucose FDG-PET^ PET scanH 7 <&, EL7]7\ FDG Glucose Transporter^ FDG FDG-PET f}-4. -6- *fi 2 g- a a FDG §14. FDG PET FDG PET7> Lowe VJ ^ 3$% 88%, 93%^]^ CT^r 63%, 80%o. HH71- ^71 ^ Malenka , FDG-PET7> ^71 x]7}7\ 1998^ Glucose transporter^] Glut-1 glucose transporter^] FDG Medline -7- MIS 1997^ ll^tj 1998^ FDG-PET1- AH«>Jl 7fl^# 1- gold standards ^>^ PETCGE Advance PET scanner)^ ^r^-^ 5§7>*>JL ^^^ ^H^ FDG ^#1^ Glucose Transporter- KGLUT-1)4] ^"€ ^ 2:^1 ^B]^^ 4i£-g: «1 i2 ^-^*>5!4. 604, ^^ 57.84)°!^^ -£!£ ^f 16^, }^ ^}, 20 1-I- ^^-* -i- gold standards ^>^ FDG-PET Positive)?! ^S^ Il7fl, ^l-g-^CTrue Negative) 237fl, ^ (False Positive) Il7fl, ^^-^(False Negative) 57fl ^ # 50 1. FDG PET Imaging FDG PET scan^r F-18 FDG 370-555(10-15mCi)l- ^^ S>aL 60^ ^«H) ^-7fl^ 7]X-]^]A^ ^^^77}^}$] ^1^1^^.^. GE Advance PET scaneKGE Medical systems, Milwaukee, WD1- °l-8-«H ^^4. PET scan^: ^l^-^(sagittal)^ 8.5mm 4.25mm ^>^^S ^i4 PET scan£ ^1 -rl^l-fe- Mountain^! regional lymph node classification for lung cancer staging^- trj- 17) > PET scan^ sfly-«|-^ «fi^-£7|- l^^]7l tqi^ofl ££ FDG ^^1- i°l 3r}7] ^*fl CT scan# ^-JlS ^Sl^l^ CT scan ^ o)^- ^: €-713. ^t^-Sl-*]^- ^XJ:J1, Standardized Uptake Value(SUV = mean selected region of activity/injected dose/body weight) 3.0 4. 2. ^r# ^ ^ ^ 1 7) ^ 7} 3. Immunohistochemistry anti-Glut-1 antibodyCMYM antiserum, Chemicon International INC, bovine serum albumin(BSA)/PBSi^i 2% normal goat serum^f -§-^11 ^£i*j 30^: nfl^^al PBSS. 4%$t 4^- 1% bovine serum albumin(BSA)/PBS^]^ 1:500^. ^t^ anti-Glut-1 antibodyCMYM antiserum)^ ^1 ^^r°l]Ai 60^- %-<£ afl^V u>^m-^-5. 2:^! ^^^r PBSS 4^% t\-%- l^-^[ U-afll- Vectastain Elite ABC rabbit kit(Vector)AS ^-^l*|-aL HematoxylinAS. countertaining^- «] 4. &*\ # *n immunohistochemical staining*!: ^¥ ^H€°fl $.°)$. (staining intensity)^ 0(^^ &•§-), l(weak), 2(moderate), 3(strong), 4C^lnL £]fe follicle^ anti-Glut-1 antibody0)] ^-S>>fl 'g^sffe ^°1] 3]-^:*>^ follicle 5] <«^^ii- §^. scales ^-^-§>^J1, ^H€°]l^ follicle^l ^H*]-^ H)-ir°ll Follicle level* 0C0%), l(l-<25%), 2(25-<50%), 3(50-<75%), 4. 3. sqofl f^^^ ^H^^l a7l(mm), ^H PET Aov ^ follicle ^^ ^5.^ SPSS programl- °]-g-*H Mann-Whitney$\ nonparametric two-sample testA -9- 507J\$) SAfcfl^- ^H^S] 3.7}^ 3-20mm(^5 10.06mm), Follicle^ ^1°^ ^S€ 77H-8- 4^3- &%s\SiSLvl, graded 1-4(^5 1.56)^1 Follicle^ ^^ €(n=16 ^5 58.6%), S^o] 0-2(^5 1.2)o]$i4(P=0.068, Mann-Whitney test). Follicle center ^ ^S^ 1-2(^51.6), ^-§-^^1 ^H^ 1-3(^5 1.33).° 3. $\v} 1 Follicle levels ^1°^ 0-3(^5 0.73), #&<% 1-20!-g- 1.6)^.3. ^H€°fl^1 Follicle center^ (n=23W 1-3(^5 1.22), ^^^(n=ll)^ ^S^o] 1 ^ &&4. 2£]i| Follicle levels ^-g-^ ^H€(n=23)<>] 1-2(^51.3), o] ^s^o] 1-40!-3- 2.09)^-3. ^^1^^.S -fi-^*!: Mann-Whitney test). -10- 3E1 Follicle F. ^-a}7J-3E. T .PVPI 7-19.mmf11 m 0-9C1 P.'J 1-9/1 9.) 1-9.fi F,) 4-p.nrnrnCi?. 4s) 1 -4f 9 fV) 0-9,(0 7.^ i-.^fi .^.^l S2. S eJ ir 2^ -7 7l Rnliirip IPVPI bJOVA-1fn = 1 -[) 7-1 Rrnrpfi 0 fil 1-3(9. rw -Vs! ~.~r*^S? I n ~~ /.. i 1 1-3(9 99^) •11- <?1^(Glucose transporter, GLUTW ^*fl nfl7fl£|^r %£.£. 1"4). H]i^i^l^H]^H £H^ ^ <&*}, ^1 Glut-1^1 4^ (over expression)^ ^Ixfol Glucose transporter^ ^i ^^3-4'13"16' ^loj-ofl^£ ^^ #o^ol]^ Glut-1 glucose transporter FDG ^ 56) E]J1 ^1A PET , 37]7} #43.7} 3- o] Glut- FDG-PET Follicle . FDG-PET £.7} FDG follicule ^^°1^18), follicular cellar ^^(proliferative index) ). Follicular celH ^^ ^^4 ^l^rl- ^- ii^t}^ follicular cell^l Glut-1 follicular cellar «1 Glut-1 lymphoid cellar ^i-g-^1 ^^ ^# H.^^] follicular hyperplasia 1-4S €-^*>3l °11- FDG PET *M1 follicle ^^ ^ follicular hyperplasia -g-o] PET -8- FDG -12- ^^AS FDG-PET # ^ ^^ °l^^r i£°J= ^S.^-^1 Glucose Transporter FDG $$7} 3711 ^7]-£l^ &£ ^ol n ^*i6.s ^4^4. SE FDG-PET Follicle «8^ ^H^^IH FDG ^#l7f ^7]-^ ^o]«.S ^4^4. HSJ14 ^H^ Follicle^ 7} &7}fbz) Q-gr ^AS 1^} Glucose Tranporter l(GLUT-l) ^^ FDG i FDG-PET^ o^ #^^] ^^l ^^4 if71 ^^<H1 Pfl^- -B-S-«r|->n , 71%, 75%JL Aq- FDG ^#]7> ^7>5lx] ^TJOL GLUT- -ffe FDG-PET^l «t^ll- 44^^, a ^^7f E]^ ^<&SLH FDG GLUT-1 %<%S.S. %*) ^^ ^-ffe GLUT-1 ^^ FDG PET ^AVSl ^^^# feo^l ^Sfl-Hfe FDG 5 s- , 71%, 75%^ AM- FDG ^#17> ^7>£|^ ^JL GLUT-1^ -T-fe FDG-PET^] tt^ll- M-^-^l0], S. ^i6l7f £]^] ^$1^4 FDG GLUT-1 %^£2. ^1 ^^r 3-Kr GLUT-1 S]^ FDG ^^* ^ PET ^A>O] ^^-^ o. ^ol7l o^sflA-]^ FDG -14- *\\ 6 g- 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 cancers 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 lymph node 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.