Tap chi Tai Mui Hpng Vi^t Nam - Volume (57-7). N°1 - March 2012 6.2. Ki't c|ua dieu (ri
- Xep nhT dg 1 vd 11 bom vdi nhi dgt ly le thdnh cdng tren 72,0%.
- Xep nhT dp III ddt ong thdng khi d^it ty Ic Ihdnh cdng Id 61.2%, TAI LiKU THAM KHAO
1. Djalilian MR el.al COOO). " 1 he atelectatic ear". Otolaryngology &
Head and Neck Surgery, Lippmcotl lViliiam& Wilkius Inc. pp.369-374.
2 KaiiMcin J el.al (1990).
"Klcktronenaplische I ilcrsachungcn 7Air Kollagenfa^ierstruktur des manschlichcn Trommel Icll is bein Adhasivprozep", Lryngol Rhinol Oiol(59). pp 333-336.
3. M a n n e r AL (2003), "Adhesive Otitis Media". A pocket guide to the
Far. Thieme-Stugalt- Newyork. pp.
6H-70
M a n n e r AL (2003), "Atelectasis and Retraction Pockets", A pocket guide (0 the Ear, Thieme-Slugall- Newyork.
pp 67-6H
Pau IIW (1995), "Middle Ear Retraction the Role of Predamaged Tympanic Membranes", Inl J Pediar Otolaryngol (SuppI 32), pp.S163- SI66
Ruah C ct.al (1992), "Mechanism of retraction pockets formation in the Pediatric Tympanic Membrane", Arch Otolaryngol Head Neck Surgery (118). pp.l298-I305.
S a d i J et.al (1981), "Atelectasis, Retraction pockets and Cholesteatoma" Ada Otolaryngol (92). Hinari. pp50l-5I2.
DOI CHIEU BIEU HIEN CUA GALECriN-3 VOff DAC DIEM LAM SANG VA MO BENH HOC CUA UNG THU THANH QUAN - HA HONG
Bui The Anh", Nguyen Dinh P h i i c " , Phan Thi Phi Phi*'"
S U M M A R Y
Galectin-3 is a member of the B-galactoside-binding mammalian lectin family with affinity lo cell surface and extracellular polylactosamine giycans. It has been shown to be involved in differentiation, morphogenesis, lumor progression, and metastasis.
Objectives: Identification of correlative involvement of galectin-3 in the neoplastic progression of patients suffered from laryngo-hypopharyngeal cancer. Materials and method: paraffin-embedded histopathological samples were collected from 56 patients diagnosed laryngo-hypopharyngeal cancer and surgically treated in Oncology Department (National ENT Hospital) from 3/2003 to 3/2005. Galectin-3 expression was analyzed by the immunohistochemical method in 56 laryngo-hypopharyngeal specimens (54 squamous cell carcinomas and 9 specimens of distinct normal mucosa). Results:
Galectin-3 expression was found in 27/56 pathological samples (48,2%)). The average of colored-density percentage was 18% (ranged from 5%i to 90%). The average colored- dye index was 0.39 (ranged from 0 to 2.7) with significant difference between research
* B§nh vi§n Tai Mui Hpng trung uang
**. BO m6n Tai MOi Hpng Dgi hpc Y Hd Npi
" ' . Bp m6n Mi^n D|ch Bgi hpc Y MS Npi - Nh0n bdi 20/1/2012 - Duy^t in 30/1/2012
2.
Tap chl Tai Mui Hpng Vi^t Nam - V o l u m e (57-7). N°1 - March. 2012 samples and controlled group (p<0.05). Expression of galectin-3 was increased in those sub- groups: elderiy patients (more than 60 years old), tumor in hypopharyngeal zone, tumor v^th extra-glottic involvement, nodal metastasis N2-N3. advanced stage S3-S4, histological grade Il-III. All the results were discussed. These results suggest that the expression of galectin-3 in histopathological samples of neoplastic progression may serve as a diagnostic as well as prognostic factor for laryngo-hypopharyneal cancer patients.
Keys w o r d s : Galectin-3, laryngo-hypopharyngeal cancer
I DAT VAN DF '*^^' " " ^ ^^^ ^^^ ^^ ^-'"^ ^^'^' ^^ ' ' ^ "
Ung ihu thanh qudn vd ha hgng la u ac linh xuat phdt chii yeu tCr te bao bieu md ciia thanh quan va ha hgng, nd dung hdng thu hai trong cac ung thu d vung dau cd sau ung thu vdm miii hgng [1][2]. Chan dodn xdc dinh ung thu thanh qudn va ung thu ha hgng bao gdm chan dodn lyp md benh hpc va chdn doan giai doan TNM[1][2]. Dieu tri benh chii yeu la phau thuat, ket hgp vdi xa tri vd hda tri lieu[2].
Viec lua chpn phuang phdp dieu tri phu thudc rat nhieu vdo chan dodn typ md benh hpc vd chan dodn giai doan ung thu.
Galectin-3 Id mdt loai protein ciia tk bao CO th^ ngudi, dugc phat hien va md td chinh thirc tir ndm 1994[3]. Nd dugc x§p vdo nhdm lectin ddng vat, cd khd nang gdn dac hieu vdi dudng p- galactoside vd cd trinh ty axit amin dac trung. Trong co the ngudi, gen ma boa cho protein galectin-3 nam tren nhiSm sdc th6 sd 14, nhdnh ddi, locus sd 2 1 - 22. Khoang mudi nam trd lai day, phan tu galectin-3 dugc nhdc d8n nhi^u trong ITnh vyc ung thu hpc. Vai trd ciia nd dugc biSu hien trong cdc qud trinh diSu hod sinh trudng 18 bao, uc chB sy chet cua t6 bao theo chuong trinh (apoptosis), tang khd nang bdm dinh ciia t6 bdo vdo cac td chirc xung quanh [4][5][6][7]. Nhd dd phan tir galectin-3 cd the tham gia vao co ch^ sinh hgc cua hien tugng lan trdn, xam Idn va di can ciia ung thu. Cd sy tuong img gifl-a lugng galectin-3 va typ md benh hpc cung nhu kha nang xam ldn va di can cua mgt sd
hod vd ung thu viin^ ddu cd[71[8][9]10].
Nhi6u tdc gid cho rdng vice dinh lugng galeclin-3 la mgt trong nhiJng ydu td gdp phan ddnh gid khd ndng xam lan va di cdn ciia cdc ung Ihu ndi chung cung nhu ung thu Ihanh qudn ha hpng noi rieng [9][10][11]. Tuy nhien d Viet Nam hipn chua cd cdng trinh nghien cuu ndo ve van de ndy. VI vdy chiing tdi da tien hanh nghien cuu ndy vdi cac muc tieu sau:
/. Bdn dinh lumtg galectin-3 trong mo ung thu thanh qudn vd ha hpng.
Doi chiiu dac diem lam sdng vd dg mo binh hoc cua khoi u v&i lu0tg galectin-3.
II. DOI TU'ONG VA PHU^ONG PHAP NGHIEN C t r u
2.L Doi tvtfng nghien ciru
La cdc benh nhan dugc chan dodn xdc dinh la ung thu thanh qudn hoac ung thu ha hpng, cd chi dinh phdu thuat khdi u tai khoa U budu-Benh vien Tai Mui Hong Trung uong tir thdng 3/2003 den thdng 3/2005.
2.1.1. Tieu chuan lua chgn binh nhdn Tat ca cdc benh nhan bi ung thu Ihanh quan hodc ung thu ha hpng, co k^t qua chan dodn xdc dinh bang gidi phau benh cd trudc vd sau phau thuat.
- Cd chi dinh phau thudt khdi u.
Tat ca cdc benh nhan dd dugc phau thuat lan ddu cat bd khdi u nguyen phdt, cd hodc khdng kem theo nao vet hach cd.
Tgp chi Tai Mui Hpng Viet Nam - Volume (57-7). N°1 - March. 2012 2.1.2. Tiiu chudn IOQI tru
- Cdc benh nhan ung thu ihanh qudn vd ha hgng nhung khdng cd chi dinh phau Ihuat lay bo khoi u.
- Cdc bpnh nhdn lai phdt sau cdc phuong phdp dieu tri khdc.
- Cdc benh nhdn co u d thanh quan hoiic ha hpng nhung khdng phai Id ung Ihu.
- Benh nhan dong ihdi co ung thu Ihir hai d viing ddu co.
Da cd 56 bpnh nhan thda mdn lieu chuan, dugc chpn vdo mau nghien cim.
Dc lam nhdm chiing. chiing tdi dd thu thap 9 mau niem mac binh thudng ciia thanh quan \ a ha hgng (lay trong bpnh pham cdt thanh qudn todn phan, dugc ddnh gid ve dai the la niem mac ldnh vd khdng dinh bdng quan sat vi the dudi kinh hien vi).
2.2. P h u o n g phdp nghien ciru De tdi dugc tien hdnh theo phuang phap nghien ciru md la, gdm ca lien cim vd hdi ciru. Cdc BN dugc lap benh an mau cd ddy dii cdc thdng tin ve:
hdnh chinh, tudi, gidi, cac trieu chimg lam sdng, phdn loai ung thu theo TNMS (UlCC 2002), cdch thuc phau thudt (cd md td chi tiet bpnh tich ve dai the) vd ket qud gidi phau benh (md td vi the). Ky ihuat ban dinh lugng galectin-3 dugc tien hdnh bang phuang phdp nhudm hda md mien dich tren lieu bdn md benh hgc diic paraffin (sir dung bd kit G A L E C T I N - 3 T H V K O T E s f cua hang MABTFXH USA) lai phdng thi nghiem Khoa giai phau benh va le
bao-Bpnh vipn K. Vdi 56 bpnh nhan, chiing tdi dd thu ihap dugc tdng cpng 65 mau mo diic paraffin dc cdt nhupm va bdn djnh lugng galcclin-3, bao gdm nhdm nghipm (56 bpnh phdm ung thu - moi bpnh nhan lay 1 bpnh phdm) vd nhdm chimg (9 bpnh pham tir niem mac lanh ciia cdc bpnh nhdn ung thu Irong nghien ciru). Moi bpnh pham dugc cat 02 lieu bdn, 1 tieu bdn nhupm hematoxylin de xdc nhan lai chan dodn vd ddnh gid dp md hpc, 1 tieu bdn nhupm hda md mien dich dc bdn dinh lugng galectin-3. Cd lieu bdn nhugm hematoxylin va lieu ban nhupm hda md mien dich deu dugc dpc mpt each rieng rC bdi 2 bac sy chuyen khoa Gidi phau bpnh - Benh vien K (sir dyng kinh hien vi quang hpc ciia hdng Olympus, cd lich hgp mdy dnh ky Ihuat sd, vat kinh x40 vd xlOO). Tren tieu ban nhupm HE: te bdo ung thu cd bao tuong bdt mdu dd, nhan bdt mau xanh dam (kiem tinh) Tren tieu ban nhupm hoa md mien dich: te bao ung thu co galectin-3 se bat mdu ndu (ca nhdn va bao luong), tc bdo ung thu khdng co galectin-3 cd nhdn mau xanh, bdo tuong khdng hipn mau.
Danh gia ket qua bdn dinh lugng gaIectin-3 theo tieu chudn qudc te ciia .xet nghiem hod md mien djch, dya tren 2 tieu chi Id mat dp vd dp lan trdn. Cu the:
- Dam dp (do bat mdu ciia galectin-3, ddnh gid tren lodn bd vi trudng vdi do phdng dai 40 ldn):
Dam do Khong bdt mSu, Bat m^u yeu.
B3t m^u Irung blnh Bat mdu manh
dm tinh (-) du'ong tinh (+) d u a n g tinh (++) d u o n g tinh (+++)
Oiem so 0 1 2 3
10
Tap chi Tai Mui Hong Vi^t Nam - Volume (57-7). N°1 - March 2012 - Dp lan tran: tinh ty le phdn tram sd te
bdo ung thu bi^u hien galectin-3 tren long sd le bdo ung thu trong mdt vi Irudng (dem trung binh tren 10 vi trudng vdi dp phdng dai 400 lan).
Tir 2 gia trj iren. chiing tdi linh ra chi sd bdt mau ciia galectin-3 theo cdng thuc nhu sau:
Chi so bat mau = (di^m sd v6 dam dp * ty le % te bao bieu hien galcctin- 3)/100.
Chi sd ndy dai dien cho kSt qua bdn dinh lugng galectin-3 tren tieu bdn md benh hgc, dugc su dung d^ tinh cdc trung binh va so sdnh vdi cdc nghien cim khdc.
Todn bd sd lieu dugc xu ly theo phuong phap thdng ke y hgc Iren mdy vi tinh vdi phdn m^m EPI. INFO 6.04.
3. L Ban dinh lirpng galcctin-3
Bang 3 . 1 . Ket qua bdn dinh lupng galectin-3 d nhPm nghien cdu
Kiem dinh sy khdc biel giua hai ly le bdng thudt todn Chi-square, kiem dinh sy khac biet giira hai trung binh bdng thuat lodn studenl-tesl.
HI. KtT QUA NGHIEN CUU Trong 56 mau ciia nhdm nghiem, cd 44 mau lay tir bpnh nhdn ung thu thanh quan (giai doan sdm S1-S2: 15/44 mau; giai doan mupn S3-S4: 29/44 mau) vd 12 mau lay tu benh nhan ung thu ha hpng (giai doan mupn 12/12 mau).
Chimg tdi da thu thap dugc 9 mau chirng la niem mac ldnh d ha hpng hodc thanh guan. Trong 9 mdu chiing cd 8 mdu lay lir BN ung thu thanh qudn (giai doan sdm S1-S2: 4/8 mau; giai doan mupn S3-S4: 4/8 mdu) va 1 mau lay tir BN ung Ihu ha hpng (giai doan mupn 1/1 mau).
Bieu hen gatedirt (dam dp bStmau)
(-)
M
(++) (+++) Tong so
Ty 1^ % s d t& bao bi4u hien galectin-3 tren tieu ban 0
29 0 0 0 29
5 0
f
0 0 1
10 0 ' 3 "
1 ; 0 4
20 0 2 ! 5 : , 0 7
30 0 0 4 0 4
40 0 0
'^""'
0 1
50 0 0 4 "
0 4
60 0 0
70 0 0
i fo 0 yw
^ fi
80 0 0 2
Tfr-
3 90 0 0 0
• 1 * ^ ! 1
Tong so 29 6 18 3 56 Kit qua ban dinh lugng galectin-3 d nhdm chirng: 1/9 mau cd bieu hien galeclin-3.
mau nay cd dam do (+), dp lan trdn la 5% sd te bao. Cdn lai 8/9 mau am tinh (khdng bieu hien galectin-3).
Bang 3.2. So sdnh ket qua bdn djnh lupng galectin-3 a hai nhbm
Bi^u tlifen gaIectrn-3 (d^m do belt m^u)
T u (+) den {+++) (-) (kh6ng b i t m4u) Ty 16 % s6 te bao bieu hi6n galectin-3 (giS tn tiring binli)
Nhom nghiem (n=56) ' 27 29 18
Nhom c h i f n g (n=9) 1 8 0,6
Tap chi Tai Mui Hpng Viet Nam - Volume (57-7). N^l
Chi so bat m^u tmng binh 0,39
- M a r c h . 2012 1 0,006 p<0,05
3.2. D o i chieu dac d i u n l a m s;nig va d p mu h t n h hpc cua u n g t h u ( h a n h quan-ha h p n n \ 6 i l u p n g g a l t c t i n - 3 (cu I l u t r o n g n g h i i n c u u nay Id c h i sn hdt m d u g a l e c t i n - 3 ) 3.2.1. Tiit'ti b{'nh nhdn
Bdng 3.3. G6i chi^u tuAi vPi chi sd bat mAu galectin-3 Nh6m t u o i
s 60 tuoi (n
> 60 tuoi (n
=35)
=21)
C h i s 6 b M m d u x ±s 0,24 + 0,51 ^ ^ 0.64 t 0,76
p < 0.05
C h l sd b:M nuiu t r u n g b i n h a n h d m B N > 60 t u o i cao htm r d ret so \ d i n h d m B N S 60 l u d i . su khac nhau cd \ nghTa I h d n g kc v d i p < 0 , 0 5 .
Bdng 3.4. €)6i chieu gidi linh vP'i galectin-3 G i c i t i n h
Nam {n=55) Ni>(n=1)
C h i s 6 b i t m d u x 0,38
1
Chl so Ixil mau trung b i n h d n h d m B N nam la 0,38; a B N nCr ( d u \ nhat t r o n g mau nghien c i a i ) la i . V i sd l u a n g B N n u cdn it nen k h d n g phdn n h d m theo dam dp va dp lan Iran cung n h u k h d n g dii d i e u k i e n t h y c hien thudt toan so sdnh.
3.2.3. Loai it
NhPm nghiem Nhpm chieng
Bang 3.5. Doi chieu logi Loai u Thanh qudn (n=44)C) Hahong(n=12)(") Niem mgc ISnh {n=9)("*)
u vP'i chi s6 bat mSu galectin-3 C h i s 6 b M m d u x ± s 0.31 ± 0 , 6 1 0,66 ± 0,69 0.006 ±0.017
(•)va{"
(•) va { "
(") va (*
p>0.05 ) p<0.05
•) p<0,05
C d hai n h d m ung t h u thanh quan vd ung t h u ha h p n g deu cd chi sd bdt mau galeclin-3 cao htm so \ d i n h d m chirng ( s y khac b i e l cd y nghTa t h d n g ke v d i p<0,05).
N h d m ung t h u ha hgng cd chi sd bat m a u cao ban n h d m u n g t h u thanh qudn tuy nhien su khdc biel la k h d n g cd y nghTa t h d n g kc ( p > 0 , 0 5 ) .
3.2.4. Vitriu
Bang 3.6. Doi chieu vi tri u vdi chi s6 bdt mdu galectin-3 Vi tri u
Thanh mon don thuan (n =15)
C h i s d bat m d u x ±s 0,073 ± 0 . 1 7 9 p < 0,05
Tap chi Tai Mui Hpng Viet Nam - Volume (57-7). N°1 - March. 2012
Lan ra ngodi vung thanh mPn (n =29) Xoang le don thuan (n =5) Lan ra ngoai vung xoang IS (n=7)
0,44 ± 0,72 0.37 ± 0 , 4 0.87 ± 0,80
Nhdm ung ihu thanh qudn cdn khu Irii d Ihanh mdn cd chi sd bdt mdu galectin-3 thap han so vdi cdc nhdm ung thu thanh qudn dd lan ra ngoai thanh mon. ung thu xoang le dan thudn. ung thu dd lan ra ngodi xoang le (khac biet cd y nghTa Ihdng ke vdi p<0.05).
3.2.5. Mire dp lan rgng vd xdm lan u
Bang 3.7. Doi chi^u muc dO lan rpng va xSm ldn u vP'i chf so bdt mau galectin-3 Mu'c dQ lan rpng vd x a m ISn u (phan d$ T)
Tl(n=5) T2 (n=10) T3(n=25) T4(n=16)
Chf s 6 bdt m a u x ± s 0,07310,179 0,44 ± 0,72 0,37 ± 0,4 0,87 ± 0,80
p < 0,05
Nhdm ung thu thanh quan khu trii mire do Tl -17 co chi sd bal mdu galectin-3 ihap hon so vdi cdc nhdm ung thu thanh qudn da xam lan va lan rdng T3-'r4 (su khac biet cd y nghTa Ihdng ke vdi p<0,05).
3.2.6. Biiu hien hach co
Bang 3.8. Dot chieu bieu hipn hach co vPi chi so b i t mau galectin-3 Bieu h i ^ n hach co (phan d o N)
NO(n=40) N l (n=5) N2 (n=9) N3 (n=2)
Chi so bdt m a u x ± s 0,35 ± 0,64
0,2 ± 0 , 4 6 0,50 ± 0 , 7 1 1 ± 0,85
p < 0 , 0 5
Nhdm ung ihu vdi bach cd nhd hodc khdng sd thay hach cd (NO-N1) cd chi sd bal mau galectin-3 thap hon so vdi nhdm ung thu da di cdn hach cd ro ret (N2-N3) (su khdc biet cd y nghTa thdng ke vdi p<0,05).
3.2.7. Giai doan u
Nhdm ung thu thanh quan khu trii giai doan SI-S2 cd chi sd bat mdu galeclin-3 thdp ban so vdi cdc nhdm ung thu thanh qudn Ian rdng S3-S4 (su khdc biet cd y nghTa thdng ke vdi p<0,05).
Bang 3.9. Doi chieu giai dogn u vp-i chi so bdt mdu galectin-3 Giai d o ^ n u (phan loai S)
S1(n = 5) S2(n = 10)
C h l s d bdt m a u x ± s 0,08 ± 0 , 1 9
0,02 ± 0,06
p < 0,05
Tap chi Tai Mui Hpng Viet Nam - Volume (57-7). N°1
S3(n = 21) S4 (n = 20)
-March. 2012
0,45 ± 0,70 0,59 ± 0,72 3.2.H. Dg md hpc u
Bdng 3.10. D i i chi6u dp mfl hpc u vP'i chl s6 bat mau galectin-3 Dp m6 hpc u
l(n = II (n l l l ( n IV (n
17)
= 24)
= 12)
= 3)
C h l s6 bdt m d u X ± 8 0,01 1 0,04
0,65 t 0,67 0,66 ± 0,85 0,15 1 0,22
p < 0,05
Nhdm ung Ihu d do nio ht>c I cd chi sd b3t mdu galectin-3 Ihap ban so \(Vi cac nhdm ung thu a dd md hoc II. Ill, IV (su khdc biet cd \ nghTa ilidng kc \{Vi p<0,05).
i \ . H \ N M A N
4 . 1 . Bieu hien ciia g:ilcctin-3 trong md ung Ihu thanh (|uan-ha hpng
Nghien ciai ciia chiing toi ve bieu hien ciia galectin-3 Irong md ung thu ihanh qudn vd ung thu ha hpng dugc lien hanh vdi ky thudt bdn dinh luang Iren lieu ban nhupm hda md mien dich (ddnh gid 3 dai lugng Id dam dp. do lan tran vd chi sd bat mdu). Ddy la mdi k\ thudl sii dung khang the ddc hieu. dii tin cay \ a da dugc nhieu tdc gid khac iren the gidi dp dung Irong nhimg nam gan ddy de danh gid galectin-3 trong md ung thu (cho tdi nay chua cd phuang phdp do ndng dp galeclin-3 trong mo ma chi cd the do nong dp galeclin-3 tu do luu thdng trong huyet Ihanh). Ket qua ban dinh lugng galectin-3 trong nghien ciru cua chiing Idi dugc su dung dc so sanh giua nhdm nghiem (mo ung thu) va nhdm chirng (md lanh viing thanh quan-ha hpng), so sanh gida hai nhdm ung thu, ddng thdi so sanh vdi ket qua nghien ciru tren cac loai ung thu khac.
Dugc tinh bdng tich ciia dam dp galectin-3 tren tieu bdn va ty le % so te bao bdt mdu galectin-3, chi sd bdt mdu cd the coi la gid In tugng trung cho lugng galcctin-3 trong md ung thu. Theo cdch tinh nhu Iren, chi sd bdt mdu cd the dao ddng tir 0 (khdng cd te bdo nao bat mdu galectin-3: dam dp 0) den 3 (100% tc bdo bdi mau galectin-3; dam d^ bdt mdu manh +++). Trong nghien ciru ciia chiing tdi, chi sd bdt mdu Irung binh d nhdm nghiem Id 0,39, cao ban ro ret so vdi nhdm chimg (0,006). Khi doi chieu vdi ddc diem lam sdng vd dp md hgc, chi sd bdt mdu tdng cd y nghia thdng ke d cdc nhdm sau:
- Tudi > 60 (so vdi nhdm ludi 5 60) - U ngodi viing thanh mdn (so vdi u
khu trii d thanh mdn don thuan) - U mire dg 12-13-14 (so vdi u muc
d p T l )
- Di cdn hach cd rd ret N2-N3 (so vdi nhdm hach cd muc NO-Nl) - Ung thu giai doan mupn S3-S4 (so
vdi giai doan S1-S2)
- Ung thu dp bipt hda trung binh/lhap (so vdi nhdm cd dp biet hda cao)
Trong ba chi so cua gaIectin-3 dugc ddnh gia, chimg tdi coi dam dp Id bieu
Tgp chi Tai MOI Hpng Vi^t Nam - Volume (57-7). N°1 - March. 2012 bien ciia galectin-3 tren b8 mdt mang te
bao, cdn dp lan trdn (ty le % t l bdo bdt mdu galectin-3) dugc coi la bi6u hipn ciia galectin-3 ndi bao (trong bdo tuong vd trong nhan). Su khdc biet vk chi sd bdt mau giiJa cac nhdm cd th6 dugc gidi thich bang cdch tdng hgp cdc co che gdy ra su khac biet vk ddm dp vd dp lan trdn.
Khi nam tren be mdt mdng tS bdo, nhd cd phan gan carbohydrate d ddu tan C, galectin-3 tao cdc mdi lien k6t vdi cdc goc lactosamin tren be mdt te bdo Ian can vd tren cdc phan tu ciia mang ludi ngoai bdo (nhu laminin, fibronectin, vitronectin...), lam tdng su bam dinh ciia te bdo u, tang khd nang xam lan vd lan rdng ciia khdi u. Ung thu thanh qudn khu trii d tang thanh mdn cd dam dp galectin- 3 trung binh thap han so vdi cac khdi u thanh quan da lan ra ngoai tang thanh mdn hodc u ha hpng, cd the giai thich do cdu true md hgc khac nhau giiia cdc tang.
Tang Ihanh mdn cu the la bd tu do cua day thanh dugc phu bdi te bao bieu md Idt Idng khdng simg hda, cdc vimg cdn lai cua thanh qudn dugc phii bdi bieu md tru gid tang cd long chuyen. Vi vay ung thu xuat phat tir cac loai te bdo khdc nhau se bieu hien galectin-3 khdc nhau.
Piantelli nghien cim djnh tinh ve bieu hien cua galectin-3 tren 73 benh nhan ung thu thanh qudn chua di can hach cd thdy galectin-3 (+) d 57,5% [39]. Ty le nay cung tuang duong ket qua nghien ciiu cua chung tdi. Khi ddi chieu lam sdng, Piantelli ihay cd su tuang iing giira bieu hien galectin-3 vdi tudi, vi tri u, mire dp lan rdng vd xam lan u (phan do T) va do md hgc cua u. Ddng thdi giua nhdm cd galectin-3 (+) va nhdm khdng bi^u hien galectin-3 cd sir khdc biet \k tien lugng (ty Ip sdng 5 nam sau md vd ty le tai phat u). Vi vay dua vdo bi6u hien cua galectin-3 cd the xdc dinh
dugc bpnh nhdn thugc nhdm cd nguy CO cao hay thap, qua dd gdp phan lien lugng bpnh[9]. Plzac nghien cim 53 bpnh nhdn (22 ung thu thanh qudn vd 31 ung Ihu hgng mieng) thay 4 3 % cd bieu hien galectin-3. Tdc gid ndy cung lim thdy s\r khdc nhau ve bieu hipn galectin-3 giita cdc nhdm tudi, loai u, miic dp xdm Idn vd lan rdng ciia u (phdn do T). di cdn hach cd, giai doan u vd do md hpc ciia u.
Theo Plzac, su bieu hien galectin-3 ty Ip vdi dp md hgc va tinh trang di cdn hach, dong thdi cd vai trd tien lugng vi nd dnh hudng den ty le sdng 5 ndm sau md vd ty Ip tdi phdt u[10]. Nghien cim ciia Delorge tren 61 benh nhan (20 ung thu thanh qudn, 10 ung thu ha hpng vd 31 ung thu khoang mieng) thay dam dp galectin-3 ty le vdi dp biet hda ciia khdi u (su khac biet cd y nghTa thdng ke vdi p<0,05) [5]. Ket qua ndy cung phu'hgp vdi nghien ciru cua chiing tdi.
Neu dam dp bieu hien cho hoat tinh cua galectin-3 tren be mdt mdng te bdo thi dp Ian trdn galectin-3 cd the coi Id bieu hien cua galectin-3 ndi bdo. Tir dd ta cd the giai thich su khdc biet giiia cac nhdm dua vdo cdc chiic ndng npi bdo ciia galectin-3. Theo Rabinovich, galectin-3 ngi bao cd the tuang tdc vdi phuc hgp ribonucleoprotein (RNP), qua dd tham gia vdo qua trinh cat ndi ARN thdng tin (cat bd cdc doan intron vd ndi cdc doan exon lai vdi nhau), lam tdng tdng hgp ARN thdng tin, nhd dd keo ddi chu trinh sinh trudng ciia ti bao.
Nghien cim ciia Krzeslak cho thdy cac tk bdo u bieu hien galectin-3 cd khd ndng khdng lai cac tdc nhan gay chet te bao theo chuong trinh (nhu khdng th8 anti-Fas, hod chat chdng ung thu staurosporine, yeu td hoai tir u TNF, tia xa, nito (II) dxit NO...).
Tdc gia nay gidi thich galectin-3 cd khd ndng ire che apoptosis do trong cau tnic
Tap chi Tai Mui Hpng Vipt Nam - Volume (57-7). N°1 - March. 2012 ciia nd co mpl doan axil amin tuong ly
cua lkl-2 (mpl loai protein dc che apoptosis), llcl-2 ndm d mdng ngodi cii;i ty the, nd lie che apopicsis bdng cdch ngdn khdng cho ty the \i.v.\] phdng ra cylochrom c. (iida Bcl-2 vd galcctin-3 cd cluing nu)( dni,in dinh l\r acid amin /Is//- Trp-Gly-Arg (aspartam. tryptophan.
gl>cine \;'i arginine) Id doan cd vai trd quan trpng trong su ire die apoptosis, Cung theo Kn^cslak, galcclin-3 cd the ire che cac cyclin A \ a E lain day nhanh qud irinh chu>cn lir pha (il (Growth) simg pha S (S\nlhcsis) ciia chu trinh te bdo dan den lam tdng phdn bao Nhd dd galcctin-3 gdp phan thuc ddy khdi u phdt Irienf?].
Nghien cuu cua Choufani tren 75 bpnh nhan ung thu (23 ung thu thanh qudn, 11 ung thu ha hong vd 41 ung thu khoang mieng) cho thay cd svr khdc bipt ve ty le te bao bdt mau galectin-3 d nhdm ung thu so vdi nhdm chiing, ddng ihdi khi so sanh cac nhdm ung thu vdi nhau thi nhdm ung thu thanh qudn-ha hpng cd i\ le % te bdo bat mdu galectin- 3 Irung binh cao hem so vdi nhdm ung Ihu khoang mieng. Dieu nay dugc lac gid gidi Ihich do su khac nhau ve ngudn goc phdi thai ciia co quan xuat phat u:
thanh qudn va ha hpng xuat phdt tu ndi bi, khoang mieng xudt phdt tir ngoai bi.
Choufani cung phat hien su tuong irng giira ly le % t^ bdo bdt mau galcctin-3 vdi phan bd T, N, do biel hda va ty Ip sdng sau md 5 ndm. Theo tac gid ndy, galeclin-3 dugc coi Id y i u id ho Irg ve lien lugng cho he phan lo^i TNMS[4]. Gillenwalcr nghien ciru 35 lieu ban ung thu (8 thanh qudn, 7 h?
hpng, 2 vdm, 10 khoang mipng, 8 hpng mieng) thdy cd biiu hipn galectin-3 tren tat cd cdc lieu bdn ung thu. Ty Ip % sd ti bdo bat mdu galectin-3 d lieu bdn ung thu thanh qudn-ha hpng dao dpng tir 16,4 den 28,8%, d lieu ban ung Ihu hpng mieng va
khoang mipng dao ddng tir 14 den 62,7%.
Ket qud ndy cijng tuang ty kel qud cua chung tni (trung binh ly Ip % te bdo bdt mau galcctin-3 CT nhdm nghipm Id 18%).
Theo Gillenwater, ty Ip bdt mdu galeelin- 3 tang ir cdc tieu bdn cd dg md hgc 1 vd II (dp dc linh trung binh va thdp). do do galeclin-3 co lien quan den khd nSng xdm lan vd di cSn ung thu[61.
V. KI<:TI.IIAN
Qua nghien cim 56 bpnh nhan ung Ihu thanh qudn-ha hgng dugc khdm vd dieu tr; tai khoa U budu - Bpnh vien Tai Mui Hgng Trung Uong, chung tin da rut ra mgt so kcl lupn sau:
5.1. Han dinh lupng galcc(in-3 trong md ung (hu bang p h u o n g phap hda md mien djch
- Dam dp bdt mdu galectin-3: 27/56 bpnh nhdn cd bieu hien gaIectin-3 (48,2%).
- Ty Ip % sd te bao bdt mdu galectin-3 tren lieu bdn: 18% (dao ddng tir 5%
din 90%).
- Chi sd bdi mdu Irung binh: 0,39 (dao ddng tir 0 den 2,7).
Cd sy khdc bii't rd ret giua nhom chiing va nhdm nghien ciiu d ca 3 gia Irj dugc thdng ke (p<0,05).
5.2. Doi chieu bieu hi('n cua galcctin-3
\ n i dac diem lam san;; \ a dp mo hpc cua ung Ihu (hanh quan-ha hong
Lu(,mg galectin-3 Idng (cd 3 chi sd dugc khdo sdt) a cdc nhdm:
Tudi > 60: lugng galeclin-3 tdng so vdi nhdm tudi ^ 60.
- Ung thu ha hgng: lugng galeclin-3 tdng so vdi nhdm ung thu thanh quan, tuy nhien sy khdc biet ve chi sd bdt mdu Id chua cd y nghTa thong ke.
Tgp chi Tai Mui Hpng Vipt Nam -Volume (57-7). N°1 - March. 2012 - Ung thu lan ra ngodi tang thanh mdn
(ung thu h^ hpng, ung thu hai tdng hodc ba tang thanh qudn): lugng galectin-3 tdng so vdi nhdm ung thu chi khu trii d thanh mdn.
- Ung thu lan rdng: lugng gaIectin-3 tdng ty le vdi miic dd T (tir TI din T4).
- Ung thu di cdn hach cd rd ret (N2- N3): lugng galectin-3 tdng so vdi nhdm ung thu chi cd hach cd NI hodc chua di cdn hach cd
- Ung thu giai doan mupn (S3-S4):
lugng gatectin-3 Idng ty Ip vdi miic dp S (tir Sl din S4), trir giai doan S2 cd chi sd bdi mdu luong duong giai doan S1.
- Ung thu cd dp md hpc II hodc III (dp biet hda trung binh): lugng galectin- 3 tang so vdi nhdm ung thu cd dp md hpc I (dp biet hda cao) hodc do md hpc IV (dp biet hda thap).
TAI LIEU THAM KHAO
1. Ngd Ngpc Lien (2000) Ung thu thanh qudn. Gidn yeu tai mui hgng. Tap III.
NXB y hoc Hd Noi 197-204.
2. Barondes S.H. ct al. (1994) Galectins: structure and function of a large family of animal lectins. -/ Biol Chem 1994: 269: 20807-10.
3. Choufani G. et al. (1999) The levels of expression of galectin-1, galectin-3 and Thomsen-Friedenreich antigen and
their binding sites decrease as clinical aggressiveness increases in head and neck cancers. Cancer 1999. 86. 2353-63.
4. Delorge S et al. (2000) Correlation of galectin-3/galectin-3-binding sites with the differentiation status in head and neck squamous cell carcinomas.
Otolaryngol Head Neck Surg 2000: 122:
834-41.
5. Gillenwater A. ct al. (1996) Expression of galectins in head and neck squamous cell carcinoma. Head Neck 1996: 18: 422-32.
6. Krzeslak A. et al. (2004) Galectin-3 as a multifunctional protein. Cell Moi Biol Letters 2004; 9: 305-28.
1. Liu F.T. et al. (2002) Intracellular functions of galectins. Biochim Biophys Acta 2002; 1572:263-73.
8. Piantelli M. et al. (2002) Lack of expression of galectin-3 is associated with a poor outcome in node-negative patients with laryngeal squamous cell carcinoma. J Clin Oncol 2002; 20: 3850-6
9. Plzak J. et al. (2000) Endogenous lectins as probes to detect differentiation-dependent alterations in human squamous cell carcinomas of the oropharynx and larynx. Int J Moi Med 2000: 5: 369-72.
10. Takenaka Y. (2004) Galectin-3 and metastasis. Glycoconj J 2004; 19: 543-9.
NGHIEN ClTU PHl/OfNG PHAP DIEU TRI PHAU THUAT U NANG VA RO GIAP LU'dl
Le Minh Ky*, Nguyen Thj To Uyen**
TOM TAT
U nang va rd giap-Iuoi Id benh ly bam sinh kha thudng gdp trong chuyen ngdnh Tai Mui Hpng. Muc tieu nghien cihi; tim hieu phuong phdp diiu tri phdu thuat, budc
*BV Tai Mui Hpng TU"'
" Bd m6n TMH Dgi hpc Y Hd NOi Nh$n bdi 25/1/2012.- Duy^t in 30/1/2012
