""- TAPCHlYDLfgCLAMSANG 108 Tap 12-562/2017
••••' Lien quan gifra cac typ mo benh hoc vdi ndng do mot so dau an ung thu- cua ung thir ph6i khong tl bao nho
™ Correlation between the histopathological types and levels of some tumor markers of non small cell lung cancer
Nguyin Trirdng Giang, Nguyen Vao Nam, o i, - n - im -T X ^, J r » ' *» J , Benhvien Quany 103 Nguyen Ng9c Trung • ^^ ./
Muc tiiu: Nhan xet ve cac typ m6 benh hpc, ndng dp mpt sd dau an ung t h u va mdi lien quan giOa chung trong ung t h u phdi khdng te bao nhd. Doi tugng vd phuang phdp: Tiin cilu, md t l cat ngang 39 trudng hpp p h l u thuat dieu tri ung t h u phdi, ed chan doan md benh hpc sau mo la ung thU phdi khdng te bao nhd. Thuc hien tai Khoa Phau t h u l t Idng nguc - Tim mach, Benh vi^n Quan y 103 trong thdi gian tU 12/2013 den 10/2016. Kit qud: Ung t h u bleu m6 tuyen chiem 69,2%, ung t h u bleu mo te bao v l y chiem 25,6%, ung thU bleu mo tuyen kem bigt hda la 2,6%, u carcinoid la 2,6%. Ndng dp mpt sd marker ung thU: CEA, Cyfra 21-1, ProGRP, SCC trung blnh l l n lUpt la 14,64 ± 5,45ng/ml; 3,99 ± 0,61ng/ml; 55,96 + 5,43pg/ml va 2,16 + 0,93ng/ml. Khdng co mdi lien quan giUa cac typ mo benh hpc va ndng dp cda CEA, CYFRA 21-1 va SCC (p>0,05), nhUng cd sU khac biet cd y nghia giijfa cac typ mo benh hpc va ndng dp eCia Pro-GRP (p<0,05). Kit lugn: Ung t h u bieu md tuyen chiem da sd trong cac typ md benh hpc ung thU phdi khong t d bao nhd. Khdng eo mdi lien quan giUa eac typ mo benh hpc va nong do cua CEA, CYFRA 21-1 va SCC, nhung cd su khIe biet co y nghTa giUa cac typ md benh hpc va ndng dp cua Pro-GRP.
TCtkhda: Ung t h u phdi khdng te bao nhd, dau an ung thu, mo benh hpc.
Summary
Objective: Remarks on histopathological types, level of some tumor markers and relationship between them in non small cell lung cancer. Subject and method: A prospective and descriptive study in 39 lung cancer patients, w/ith confirmed postoperative histopathological diagnosis of non small cell lung cancer, in theDepartmentof Cardiothoracic surgery. Military Hospital 103 from December 2013 to October 2016. Result: Adenocarcinoma was 69.2%, squamous cell carcinoma was 25.6%, poorly differentiated carcinoma was 2.6% and carcinoid tumor was 2.6%. Level of tumor markers: CEA, Cyfra 21- 1, Pro-GRP and SCC were 14.64 ± 5.45ng/ml; 3.99 ± 0.61 ng/ml; 55.96 ± 5.43pg/ml and 2.16 ± 0.93ng/ml, respectively. No correlation between the histopathological types and level of CEA, CYFRA 21 -1 and SCC (p>0.05), but there was a correlation between the histopathological types and level of Pro-GRP (p<0.05).
Conclusion: Adenocarcinoma is the most in the histopathological type of non small cell lung cancer.
There is no correlation between the histopathological types and level of CEA, CYFRA 21-1 and SCC, but there is a correlation between the histopathological types and level of Pro-GRP.
Keywords: Non small cell lung cancer, tumor marker, histopathology.
Ngdy nhgn bdi • 09/02/2017. ngay chap nhan ddng: 16/02/2017
Ngucriphdn hoi: Nguyen Trucmg Giang, Email: [email protected] - Benh vien Qudn y 103
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.l2-N''2/20I7
I.Datvande
Ung t h u phoi nguyen phlt chiem X)f le cao nhat va cung la nguyen nhan g l y tU vong hang dau trong tat c l cae loai benh ung thU Do vay, can phli ehan doan sdm loai benh ly nay, ngay tU giUa nhOng n I m cua t h ^ l ^ XX, cac t i c g i l d l sU dung mdt sd marker (dau an) ung thu de chan d o l n cac loai ung thU khac nhau vl cac marker ung thU la cae chat tang cao trong co the khi xuat hien cle td bao ung thU. Mdt sd marker thudng sU dung trong chan d o l n ung thU phdi la CEA (Careino embryonic antigen), CYFRA 21-1 (Cytokeratin fragment 19), Pro-GRP (Pro-gastrin releasing peptide) va SCC (Squamous cell carcinoma antigen)... Gil trj chan d o l n cda cle marker ung thu cung nhU sU lidn quan cila chung vdi cle t;?p md bdnh hpe eua ung thU phdi van la van de dugc cle tac g i l quan tam. Vi vay, chung tdi tidn hanh nghien cdu nay vdi mue tieu Nhdn xet cdc typ mo binh hgc, nong dd mot so marker ung thU vd moi liin quan giCfa chung trong ung thuphoi khdng tibdo nhd c6 chi dinh phau thuat.
2. Doi tuTOng va phuong phap 2.1.£>o/tu'phg
Gdm 39 trudng hpp dugc phau t h u l t dieu t n ung t h u phoi, cd chan doan md benh hpc sau mo la ung t h u phdi khdng te bao nhd, tai Khoa Phau t h u l t Idng ngUc - Tim mach, Benh vien Quan y 103 trong thdi gian tU 12/2013 den 10/2016.
2.2. PhUc^g phdp Tien cUu, md t l cat ngang.
2.3. Cdc chi tieu
Danh g i l khdi u tren CT - scans Idng ngUe.
Xet nghidm marker ung thU: CEA, CYFRA 21-1, Pro-GRP and SCC
Ket q u i ele typ md benh hpc sau phau t h u l t . So sanh su lien quan giUa cac typ md benh hpc va mdt sd marker ung thu.
2.4. Phuang phdp xifl^ so lieu Sd lieu dupc xd ly tren phan mem SPSS 20.0.
3. Ket qud
Mdt sd dac diem khdi u tren CT - scans Idng nguc Vitri khoi u
BIng I.Vitrikh^iu Vitri
Phoi phSi Phoi trSi
T6ng
So lUtfng 25 14 39
TJie%
64,1 35,9 JOO Khdi u t h u d n g gap d phoi p h l i , chiem 64,1%, phdi t r l i ft hPn, chidm 35,9%.
Kich thudc khoi u
B i n g 2. Kicli thudc khoi u Kich thudc u
(cm)
<3cm 3 - 5 c m 5 - 7 c m
>7cm T6ng X ±SD
So lUdng 19 16 3 1 39
TJIe%
48,7 41,0 7,7 2,6 100 3,8 ±1,5 Kich thi/ac kh6i u trung binh la 3,8 ± 1,5cm, phan I6n l<ich thKdc I<h6i u < 3cm (Tl), chiem 48,7%;
chi gap 2,6% Ithoi u >7cm Cr3).
7y l§ c6c typ mo benh hoc sau phau thuat B i n g 3. Ty le cac typ mo bf nh hoc Typ mo benh hoc
Ung thu bieu m6 (UTBIW) tuyen Ung t h u bieu mo te bao v^y Ung t h u bieu md tuy^n kem biet hoa U carcinoid
long
SolUtfng 27 10 1 1 39
T$le%
69,2 25,6 2,6 2,6 too UTBIVI tuyen (69,2%) chiem t J le cao nhat, sau do den UTBIW te bao vSy (25,6%). Co 1 trUtJng hop u carcinoid dien hinh (2,6%).
So sanh su lien quan glufa cac typ mo bSnh hgc va nong do mot so dau ^n ung t h u .
TAP CHl Y DUOC U M SANG 108 Tap 12-So 2/2017
B i n g 4. SU lidn quan giuTa cic typ mo b f nh hoc va nong 6p CEA
^ ^ _ _ ^ ^ CEA (ng/ml) Nhom ^ " " " " ~ ~ ^ ^ ^ ^ ^ ^
UTBM tuySn UTBM te bao vay UTBIVI tuyen kem bi^t hoa U carcinoid
Tong P
n
25 3 1 1 35
Trung vi
7,05 3,70 1,72 2,78 3,92
X ± S D
18,35 ±7,51 6,15 ±2,27
1,72 2,78 14,64 + 5,45
Min
1,25 0,76 1,72 2,78 0,76
Max
148,06 19,58 1,72 2,78 148,06 0,774
Nong do CEA trung blnh la 14,64 ± 5,45ng/ml. Trong do UTBIVI tuyen la 18,35 ± 7,51 ng/ml, ung t h u bieu m6 (UTBM) te bao v i y la 6,15 ± 2,27ng/ml (co 10 truSng hop la UTBM t6 bao vSy nhUng chi CO 8 trudng hop lam CEA). Nong dp CEA 6 cac t y p mo benh hpc khac nhau khong Co y nghia thong kg vdi p>0,05.
V6iCyfra21-t
B i n g 5. SU lien quan gitJTa cic t^p mo benh hoc va nong d6 Cyfra21-1
~~~~~->,,^^ Cyfra21-1 (ng/ml) Nhom ^~"~~~---...,^
UTBM tuyen UTBM te bao vay UTBM kem biet hoa U carcinoid
Tong P
n
25 8 1 1 35
Trung vj
3,12 3,14 7,55 2,48 3,12
X ± S D
3,58 ± 0,54 5,03 ± 2,08
7,55 2,48 3 , 9 9 ± a , 6 I
Min
1,17 1,04 7,55 2,48 T,04
Max
13,76 19,34 7,55 2,48 19,34 0,564
Nong do Cyfra 21 -1 trung blnh la 3,99 ± 0,61 ng/ml, UTBM tuyen la 3,58 ± 0,54ng/ml, UTBM te bao vSy la 5,03 ± 2,08ng/ml (co 10 trudng hop la UTBM t l bao vay nhung chi co 8 trudng hpp lam Cyfra21-1). Nong d d Cyfra 21-16 cac typ mo bSnh hpc khac nhau khdng co y nghTa thong ke vOi p>0,05.
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.l2-N"M017
Binge.SUlienquangitJTacictypmd benh hoc va nong do Pro-GRP
^~^~~--—^,^o-GRP(ng/ml) Nhom ^~~"~-^~..^^^
UTBM tuyen UTBM te bao Vciy UTBM kem biet hoa U carcinoid
T6ng P
n
25 7 1 1 34
Trung vi
45,50 44,98 37,35 147,72 45,24
X ± S D
54,74 ±7,02 49,86 + 7,33 37,35 147,72 55,96 ± 5 , 4 3
0,027
Min
30,15 27,00 37,35 147,72 27,00
Mai
147,57 82,00 37,35 147,72 147,72
Ndng do Pro-GRP trung binh la 55,96 ± 5,43pg/ml, eao nhat d UTBM tuyen vdi 54,74 ± 7,02pg/ml, UTBM t d bao v l y I I 49,86 + 7,33pg/ml {cd 10 trUdng hpp la UTBM te bao v l y nhUng ehi ed 7 trudng hpp lam Pro- GRP). Ndng dp Pro-GRP d eae typ md benh hoc khIe nhau ed y nghla t h d n g ke vdi p<0,05.
Vdi SCC
Bang 7. Sir lien quan giiira c l e t y p mo benh hoc va ndng do SCC
" ~ ~ ~ ~ - - - . „ ^ ^ SCC (pg/ml) Nhom ^"^"^--^.^^^
UTBM tuy^n UTBM tebJo vay UTBM kem bm hoa U carcinoid
Tong P
n
23 6 1 1 31
Trung vj
0,90 1,40 0,60 1,50 0,90
X ± S D
1,29 + 0,31 5,85 ± 4,63 0,60 1,50 2,16±a,93
0,287
Min
0,40 0,50 0,60 1,50 0,40
Max
7,90 29,00 0,60 1,50 29,00
Ndng dp SCC trung binh la 2,16 ± 0,93ng/ml, cao nhat cl typ UTBM te bao v i y (5,85 ± 4,63ng/ml) (c610 trudng hop la UTBM te bao vSy nhUng chi cd 6 trUdng hpp lam SCC), UTBM tuyen (1,29 ± 0,31 ng/ml). Nong dd SCC 4 cac typ mo benh hpc khac nhau khdng c6 y nghta thong ke vdi p>0,05.
TAPCHlYDaOCLAMSANGlOS T^p 12-56 2/2017
4. Ban l u a n
Ddc diim dgi the khoi u trin CT- scans long ngUc Vj trf khdi u: Trong nghien edu nay, khdi u thudng gap d phdi p h l i vdi 64,1 %, phdi t r l i la 35,9%.
Ket q u i nay t u o n g dUong vdi mpt sd t i e g i l khac.
Nguyen Hdng Phuc [7] nghien cUu 81 benh nhan, khdi u d phoi p h l i la 61,7%, phoi t r l i la 38,3%.
Nguyen Hoai Nam [6] nghien eUu 60 benh nhan: U d phdi phai la 58,3%, phoi t r l i II41,7%. Bui Chi Viet [8]
nghien cdu 299 benh n h i n thi t y le u nam d phdt p h l i I I 63,9%, phdi t r l i la 36,1%.
Kich thudc khdi u: Kdt q u i nghien eUu cho thay kfch thude khdi u trung binh la 3,8 ± 1,5cm. Phan Idn khdi u cd kich thude < 3em, ehiem 48,7%; 41,0%
benh nhan cd khdi u tU 3 den < Sem; sd benh n h i n cd khdi u tren 7em chi ehiem 2,6%. Ket q u i nghien cUu cCia chung tdi t u o n g duong vdi cac t i e g i l khIc.
Nguyen Hdng Phuc [7] cdng b d 65,4% khdi u cd kfeh thudc 3 - 6cm, 27,2% khdi u cd kich thude tren 6cm.
Bui Chi Viet [8] ghi nhan 86,3% khdi u cd kich thUdc tren 3em.
Cdc Vf'p mo benh hgc
Kix q u i eho thay UTBM tuyen ehiem ty le cao vUpt trdi vdi 27 trudng hpp chidm 69,2%; tiep den UTBM te bao v l y vdi 10 trudng hpp ehiem 25,6%.
K^t q u i n l y h o l n toan phiJ hpp vdi cac nghien cUu cCia mdt so tac g i l khIc. Nghien eUu cda Nguyen Hoai Nam [6] t h I y cd 73,3% UTBM tuyen; 26,7%
UTBM t d bao v l y . H o I n g Ngpc H I i [2] nghien eUu 40 benh nhan, cd 85% UTBM tuyen, 10% UTBM te bao vay. Bui Chf Vidt [8] nghien cUu 299 bdnh nhan, cho thay UTBM tuyen chrem 55,5%, UTBM te bao vay chiem 15,6%.
Trong nghien eUu nay cd 1 trudng hpp u carcinoid phdi dien hinh (2,6%). U carcinoid nam trong Idng phe q u I n cd hinh dang ben ngoai tron lang, m l u d d I n h dao, dang polyp, day I I dang tdn thupng hiem gap, chiem 1 - 2% ung thU d phdi. U carcinoid phdi hay con gpi u than kinh ndi tiet carcinoid khi phe quan, ed 2 dang ehinh la u carcinoid dien hinh vdi mdc d d I c tinh thap va u carcinoid khdng diin hinh vdi mUc dp ac tinh trung blnh. Theo Nguyen Hijfu Lan [5] t d 2008 - 2013 tai Benh vien
Pham Ngpe Thach ghi nhan 4 trudng hpp u carcinoid dien hinh va 20 trUdng hpp khdng dien hinh.
Ddnh gid sU lien quan giCfa nong do mdt so marker ung thU vdi cac t;^p md binh hgc
Ndng d d CEA: Ket q u i nghien cUu eua ehung tdi thay ndng dp CEA trung binh la 14,64 ± 5,45ng/ml (td 0,76 ddn 148,06ng/ml), trung vi 3,92ng/ml. Trong dd ndng dp CEA theo nhdm md benh hpc thi UTBM tuyen la 18,35 ± 7,51 ng/ml, UTBM te b i o vay la 6,15
± 2,27ng/ml. Khdng cd sU khac biet ndng dp CEA d cac nhdm md benh hpc ung t h u phdi (p>0,05).
Ndng dp CEA trong nghien eUu eua chdng tdi tupng duong vdi ket qua cOa Nguyen Minh H I i [3] nghien cUu d benh n h i n ung t h u phdi ndi ehung thay ndng d d CEA la 29,27 ± 43,83ng/ml. Nguyen H I i Anh [1]
nghien cdu d 123 benh n h i n , cho ket q u i nong dp trung binh CEA I I 30,43 ± 36,69ng/ml, d nhdm chdng benh phdi khdng ung thU la 1,37ng/ml.
Ndng dp CYFRA 21-1: Ndng dp Cyfra 21-1 I I 3,99
± 0,61ng/ml (tU 1,04 ddn 19,34ng/ml); trung vj 1a 3,12 ng/ml.
Ket q u i nghien cUu cda ehung tdi thap hon vdi nghidn cdu eda t i c g i l Hang Z.Q [9] nghidn cUu 102 benh nhan ung thU phdi, ndng dp Cyfra 21-1 la 14,08 ± 8,34ng/ml va tae g i l Huang M.S [10], nghien cUu 80 benh n h i n , ndng dd Cyfra 21-1 la 13,26 ± 16,54ng/ml.
Trong nhdm benh nhan nghien eUu, ndng dp Cyfra 21-1 khdng ed sU khIc nhau giUa cac typ m d benh hpc vdi p>0,05. Cu the, ndng dd Cyfra 21-1 nhdm UTP t d bao vay la 5,03 ± 2,08ng/ml; trung vj la 3,14ng/ml trong khi ndng do Cyfra 21-1 nhdm UTP bieu md tuyen la 3,58 ± 0,54ng/ml, trung vi 3,12ng/ml. Ket qua nay tUOng tU vdi nghien cUu cda t i c gia Lai R.S [11].
Nong dp Pro-GRP: Trong nghien eUu eda chdng tdi, nong dp Pro-GRP trung binh I I 55,96 ± 5,43pg/ml (td 27,0 den 147,72pg/ml). Nong dp Pro- GRP d UTBM tuyen I I 54,74 ± 7,02pg/ml, trung vj la 45,5pg/ml; UTBM te bao v l y la 49,86 ± 7,33pg/ml, trung vj I I 44,98pg/ml. Nong dp Pro-GRP d ele t;/p md benh hpc k h I c biet cd y nghTa thdng kd vdi p<0,05. Ket qua nghidn cdu eda Hoang Trung Kien [4] tren 81 bdnh n h i n cho thay ndng dp Pro-GRP la
35
lOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.l2-N"2/2017 ^
56,18 ± 24,94pg/ml; trung vj la 50,55pg/ml (24,31 - 187,53pg/ml}.
Ndng dd SCC: Ket qua nghien cUu xac djnh ndng dp SCC I I 2,16 ± 0,93ng/ml (tU 0,40ng/ml den 29,0ng/ml); trung vi la 0,90ng/ml. Trong dd ndng dp SCC cao nhat d UTBM te bao v l y (5,85 ± 4,63ng/ml), sau dd la UTBM tuyen (1,29 ± 0,31 ng/ml). Khdng cd su khac biet ndng do SCC 6 cle typ md b&nh hpc vdi p>0,05.
K^t q u i cua chung tdi phu hpp vdi nghien cUu CLia tac g i l Moro D [12], gia trj trung vj ndng dp SCC la l,2ng/ml. Neu lay ndng dd SCC I I 3ng/ml lam ngudng thi ket qua cua ehung tdi cd 2/31 (6,5%) benh nhan cd gia tri SCC cao hon 3ng/ml. Hoang Trung Kien [4] nghien cUu 81 benh nhan ung thU phdi khdng te bao nhd thay ndng dp SCC la 2,76 ± 4,9ng/ml; trung vj la l,2ng/ml (tU 0,3 den 34,8ng/ml).
5. K^t luan
Qua nghien cUu 39 trudng hpp ung thU phdi khdng te bao nhd cho thay:
Ung t h u bieu md tuyen chidm tJ- le cao nhat (69,2%), sau dd den ung t h u bleu md te bao v l y chidm 25,6% trong ele typ ung thU phdi khdng te bao nhd cd chi djnh phau t h u l t .
Khdng ed mdi lien quan gida cle typ md benh hpc va ndng dp cda CEA, CYFRA 21-1 va SCC, nhung cd su khIc bidt cd y nghla gida cle ti^p md benh hpc va ndng dp cua Pro-GRP.
Tai Ii0u t h a m khao
1. Nguyen Hai Anh (2007) Nghien cOu gid tri ctia Cyfra 21-1 vd CEA trong chdn dodn vd theo doi ung thu phe qudn nguyen phdt. Luan an Tien sy Y hpe, Dai hpc Y Ha Npi.
2. Hoang Ngpc Hai (2016) Ddnh gid kit qud phdu thudt ngi soi cdt thiiy phoi trong diiu tri ung thu phoi khdng ti bao nhd. Luan van Thac sy Y hpc, Hpc vien Quan Y.
3. Nguyen Minh Hai (2010) Nghien ciru gid tri cua CEA, TPS, PSS, EGFR trong dinh hUdng chan dodn vd tiin
lugng ung thUphoi khong ti bdo nhd. Luan an Ti^n sTY hpc, Hpc vien Quany.
4. Hoang Trung Kien (2014) Nghiin cdu nongdAnidt so ddu dn ung thu (tumor marker) huyet tuang d binh nhdn ung thu phoi nguyin phdt. Luan van Thac sy Y hpe, Hpc vien Quan Y.
5 Nguyen Hdu Lan va cpng sU (2014) Bieuhlenldm sdng. ngi soi phi qudn, hinh dnh hoc va tiin luang cixa u thdn kinh ngi tiet carcinoid khi phi qudn phoi dien hinh vd khong dien hlnh. Tap chi Y hpc TP HCM,tap18,sd1,tr.30-37.
6. Nguyen Hoai Nam (2003) Nghiin cdu hinh tMigidi phau binh vd Idm sdng cua benh ung thuphSi duBc dieu tri bdng phdu thudt. Tap chi Y hgc TP. Ho Chi Minh. Tap 7, Phu b i n eCia sd 4, tr. 61-68.
7. Nguyen Hdng Phdc (2011) Nghiin cHu dgc diim idm sdng, md binh hgc vd hda mo mien dich trong ung thu ph6i tai Binh vlin 103. Luan van Thac sy Y hoc, Hpc vien QuIn Y.
8 Bui Chi Vi^t, Diep Bio Tuin, Man Phd Dilc (2003) Phdu tri ung thU phoi nguyin phat khdng te bdo nho. Tap chi Y hpc TP. Hd Chi Minh. Tap 7, Phu bSn cLiasd4,tr. 51-58.
9. Hang ZQ (2011) Detection and diagnostic value of serum carcinoembryonic antigen and cytokenatin 19 fragment in lung cancer patiens. Zhonghua Zhong Liu ZaZhi 33(11): 847-849.
10. Huang MS (1996) Cytokenatin fragment 19 (CYFRA21-1) as a tumor marker in non small cell lung cancer. Kaohsiung J Med Sci 12(2): 62-68.
n . Lai RS et al (1996) CYFRA 21-1 enzyme-United immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer. Chest 109(4}:
995-1000.
12. Moro D et al (1995) CEA, CYFRA21-1 andSCCmnon- small cell lung cancer. Lung cancer 13(2): 169-176.
