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ORLI Vol. 45 No. 1 Tahun 2015 Ekspresi E-cadherin pada metastasis karsinoma nasofaring
27
ABSTRAKLatar belakang: Karsinoma Nasofaring (KNF) adalah keganasan dengan distribusi etnis dan
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Kata kunci:�.DUVLQRPD�QDVRIDULQJ��HNVSUHVL�(�FDGKHULQ��PHWDVWDVLV
ABSTRACTBackground: Nasopharyngeal carcinoma (NPC) is a malignancy with distinct ethnic and
geographical distribution. NPC has different characteristics from other head and neck cancers, such as rapid growth behavior, high propensity to metastasize to regional lymph nodes and distant organs. E-cadherin plays an important role in the maintenance of cell adhesion between epithelial cells. Changes in the cell adhesion molecule E-cadherin mediated by cancer cells contributes to increase in the spread of tumor cells and the formation of metastasis. Purpose: To determine the difference in the expression of E-cadherin between NPC that has metastasized and NPC that has not metastasized. Method: A FDVH�FRQWURO�VWXG\��6XEMHFWV�ZHUH�SDUDI¿Q�EORFNV�IURP�13&�SDWLHQWV�ZKR�KDG�XQGHUJRQH�ELRSV\��%ORFNV�from NPC patients who had metastasized categorized as a group of cases, while not metastasized as a control group. Samples from both groups were examined using immunohistochemistry method (IHC) with antibody E-cadherin. Result:�6DPSOHV�ZHUH����SDUDI¿Q�EORFNV��HDFK�JURXS�FRQVLVWHG�RI����EORFNV��7KHUH�ZDV�D�VLJQL¿FDQW�GLIIHUHQFH�EHWZHHQ�WKH�H[SUHVVLRQ�RI�(��FDGKHULQ�ZLWK�S�������DQG�2GGV�5DWLR��52������������FRQ¿GHQFH�LQWHUYDO�������WR�����������7KHUH�ZDV�DOVR�D�VLJQL¿FDQW�FRUUHODWLRQ�EHWZHHQ�UHGXFHG�H[SUHVVLRQ�RI�(�FDGKHULQ�ZLWK�QHFN�O\PSK�QRGH�VWDWXV��S���������GLVWDQW�PHWDVWDVLV��S ��������DQG�VWDJH�RI�GLVHDVH��S ��������Conclusion:�7KHUH�ZDV�D�VLJQL¿FDQW�GLIIHUHQFH�EHWZHHQ�WKH�H[SUHVVLRQV�of E-cadherin in NPC that had metastasized with the NPC that had not metastasized.
Keywords: Nasopharyngeal carcinoma, E-cadherin expression, metastasisAlamat korespondensi:�&DPHOLD�+HUGLQL��%DJLDQ�,.�7+7�./�)DNXOWDV�.HGRNWHUDQ�8QLYHUVLWDV�*DGMDK�0DGD��HPDLO�FDPHOLDBKHUGLQL#\DKRR�FRP
Laporan Penelitian
Ekspresi E-cadherin pada metastasis karsinoma nasofaring
Taufiqurrahman*, Camelia Herdini*, Bambang Hariwiyanto*, Harijadi** 'HSDUWHPHQ�7HOLQJD�+LGXQJ�7HQJJRURN���%HGDK�.HSDOD�/HKHU�)DNXOWDV�.HGRNWHUDQ��������
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ORLI Vol. 45 No. 1 Tahun 2015 Ekspresi E-cadherin pada metastasis karsinoma nasofaring
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Tabel 1. Karakteristik subjek penelitian
Karakteristik subjek Kasusn (%)
Kontroln(%)
Totaln(%)
Nilai p
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3. Jenis histopatologi :+2�WLSH�,��������:+2�WLSH�,,��������:+2�WLSH�,,,
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Ekspresi E-cadherin pada metastasis karsinoma nasofaringORLI Vol. 45 No. 1 Tahun 2015
PENDAHULUAN
Karsinoma Nasofaring (KNF) PHUXSDNDQ� VXEWLSH� \DQJ� EHUEHGD� GDUL�.DQNHU� .HSDOD� /HKHU� �../�� GDODP� KDO�HSLGHPLRORJL�� NDUDNWHULVWLN� NOLQLV�� HWLRORJL��GDQ� KLVWRSDWRORJL�� (WLRORJL� .1)� VDQJDW�NRPSOHNV��PHQFDNXS�IDNWRU�JHQHWLN��LQIHNVL�(SVWHLQ�%DUU�9LUXV��(%9���GDQ�OLQJNXQJDQ����
,QVLGHQV�.1)�GL�,QGRQHVLD�GLSHUNLUDNDQ������������� DWDX� VHNLWDU� ������ NDVXV� EDUX�VHWLDS� WDKXQQ\D�� Dari data rekam medik SROLNOLQLN� 7HOLQJD� +LGXQJ� 7HQJJRURN� ��.HSDOD� GDQ� /HKHU� 5XPDK� 6DNLW� 8PXP�3XVDW� 'U�� 6DUGMLWR� <RJ\DNDUWD�� GDODP� WLJD�WDKXQ� WHUDNKLU� GLGDSDWNDQ� MXPODK� SDVLHQ�\DQJ� WHUGLDJQRVLV� .1)� SDGD� WDKXQ� �����VHEDQ\DN� ��� SDVLHQ�� WDKXQ� ����� DGD� ���SDVLHQ��VHGDQJNDQ�SDGD�WDKXQ������VHEDQ\DN����� SDVLHQ�� 'DWD� WHUVHEXW� PHQXQMXNNDQ�SHQLQJNDWDQ�MXPODK�SDVLHQ�.1)�GDODP�WLJD�WDKXQ�WHUDNKLU�
0HWDVWDVLV� PHUXSDNDQ� SHQ\HEDE�NHPDWLDQ� ���� GDUL� VHPXD� NDQNHU� GDQ�PHQLPEXONDQ� JHMDOD� NOLQLV� \DQJ� EHUEHGD�� 0HWDVWDVLV� PHQXQMXNNDQ� SURVHV� \DQJ�WHUNRRUGLQDVL�� PHPLOLNL� WDKDSDQ�WDKDSDQ��PHOLSXWL� SHPLVDKDQ� VHO� GDUL� WXPRU� SULPHU�XQWXN� EHUNHPEDQJ� PHQMDGL� OHVL� EDUX� GL�RUJDQ�MDXK��
%HUEHGD� GHQJDQ� .DUVLQRPD� 6HO�6NXDPRVD� �.66�� NHSDOD� OHKHU� ODLQQ\D��SHUWXPEXKDQ� WXPRU� \DQJ� FHSDW�PHQ\HEDENDQ�.1)�PHPLOLNL�NHFHQGHUXQJDQ�\DQJ� WLQJJL� XQWXN�PHQJLQYDVL� GDHUDK� \DQJ�EHUGHNDWDQ��EHUPHWDVWDVLV�NH�NHOHQMDU�JHWDK�EHQLQJ� �.*%�� UHJLRQDO� GDQ� RUJDQ� MDXK�� /HELK� GDUL� ���� SDVLHQ� .1)� \DQJ� GDWDQJ��WHUGLDJQRVLV� GHQJDQ� PHWDVWDVLV�� -LND� WHODK�WHUMDGL�PHWDVWDVLV��PDND�SURJQRVLV�SHQ\DNLW�PHQMDGL� MHOHN� GDQ� PHQ\HEDENDQ� WLQJNDW�NHJDJDODQ� WHUDSL� \DQJ� WLQJJL�� 2OHK� NDUHQD�LWX�� SHPDKDPDQ� \DQJ� OHELK� EDLN� WHQWDQJ�mekanisme molekuler metastasis KNF VDQJDW�SHQWLQJ�XQWXN�PHPSHUEDLNL�SURJQRVLV�SDVLHQ����
$GKHVL� DQWDUVHO� PHPDLQNDQ� SHUDQ�SHQWLQJ�GDODP�SHPHOLKDUDDQ�LQWHJULWDV�VHO�GDQ�MDULQJDQ��� %HEHUDSD� PROHNXO� DGKHVL� GLDNXL�VHEDJDL� SHQDQGD� XQWXN� SRWHQVL� NHMDGLDQ�PHWDVWDVLV� WXPRU�SDGDW���(�FDGKHULQ� DGDODK�VDODK� VDWX�JOLNRSURWHLQ� WUDQVPHPEUDQ�\DQJ�SHQWLQJ�GDODP�DGKHVL�VHO��tumor suppression��GLIHUHQVLDVL� VHO�� GDQ�PLJUDVL� VHO�� 3HQHOLWLDQ�WHUEDUX�GDUL�SURWHLQ�LQL�PHQXQMXNNDQ�EDKZD�SHQXUXQDQ� HNVSUHVL�(�FDGKHULQ�PHPDLQNDQ�SHUDQ� GDODP� SHUNHPEDQJDQ� GDQ�PHWDVWDVLV�WXPRU��3HUXEDKDQ�LQWHUDNVL�DQWDU�VHO�GDQ�VHO�GHQJDQ�PDWULNV�PHPEHULNDQ�NHPDPSXDQ�VHO�NDQNHU�XQWXN�PHOHZDWL�EDWDV�MDULQJDQ�QRUPDO�GDQ� EHUPHWDVWDVLV�� $GDQ\D� SHUXEDKDQ�NXDOLWDWLI�GDQ�NXDQWLWDWLI�GDODP�HNVSUHVL�GDQ�IXQJVL� PROHNXO� DGKHVL� VHO� \DQJ� GLPHGLDVL�ROHK�(�FDGKHULQ�PHUXSDNDQ�SHQDQGD�SHQWLQJ�DGDQ\D� SRWHQVL�PHWDVWDVLV� EHEHUDSD� NDQNHU�VHSHUWL� NDQNHU� ODPEXQJ�� NDQNHU� NRORUHNWDO��.66�NXOLW��GDQ�NDQNHU�SD\XGDUD������ Namun GHPLNLDQ�� SHQJJXQDDQ� (�FDGKHULQ� VHEDJDL�SHQDQGD�SDGD�.1)�EHOXP�SHUQDK�GLODSRUNDQ��3HQHOLWLDQ� LQL� EHUWXMXDQ� XQWXN�PHQHQWXNDQ�SHUEHGDDQ�HNVSUHVL�(�FDGKHULQ�DQWDUD�.1)�\DQJ�VXGDK�EHUPHWDVWDVLV�GHQJDQ�.1)�\DQJ�EHOXP� EHUPHWDVWDVLV� GDQ� PHQJHYDOXDVL�SHPDQIDDWDQ� (�FDGKHULQ� VHEDJDL� SHQDQGD�PHWDVWDVLV�SDGD�.1)�
METODE
5DQFDQJDQ� SHQHOLWLDQ� \DQJ� GLJXQDNDQ�adalah case-control study� �NDVXV�NRQWURO���GHQJDQ�VDPSHO�SHQHOLWLDQ�DGDODK�EORN�SDUD¿Q�SDVLHQ� .1)� \DQJ� WHODK� PHQMDODQL� ELRSVL�EDLN�\DQJ�PHQJDODPL�PHWDVWDVLV��NHORPSRN�NDVXV��PDXSXQ�WLGDN�PHQJDODPL�PHWDVWDVLV��NHORPSRN�NRQWURO����
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ORLI Vol. 45 No. 1 Tahun 2015 Ekspresi E-cadherin pada metastasis karsinoma nasofaring
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Tabel 1. Karakteristik subjek penelitian
Karakteristik subjek Kasusn (%)
Kontroln(%)
Totaln(%)
Nilai p
1. Jenis kelamin �/DNL�ODNL��������3HUHPSXDQ
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2. Umur ������WDKXQ��������!���WDKXQ
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3. Jenis histopatologi :+2�WLSH�,��������:+2�WLSH�,,��������:+2�WLSH�,,,
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ORLI Vol. 45 No. 1 Tahun 2015 Ekspresi E-cadherin pada metastasis karsinoma nasofaring
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Tabel 2. Analisis ekspresi E-cadherin terhadap kelompok kasus dan kontrol
Ekspresi E-cadherin Kasusn (%)
Kontroln(%) Nilai p Odd Ratio
(IK 95%)Negatif ���������� �������� ������ ���������������������Positif �������� ����������
*bermakna p�����
3DGD� WDEHO� ��� HNVSUHVL� (�FDGKHULQ�SRVLWLI� GLWHPXNDQ� SDGD� ��� EORN� SDUDILQ�GDQ� HNVSUHVL� (�FDGKHULQ� QHJDWLI� VHEDQ\DN���� EORN� SDUDILQ� \DQJ� WHUEDJL� PHQMDGL� ���NHORPSRN��3DGD�NHORPSRN�NDVXV��VHEDQ\DN����EORN�SDUDILQ���������\DQJ�GLQLODL�VHEDJDL�HNVSUHVL�QHJDWLI�GDQ���EORN�SDUDILQ���������\DQJ�GLQLODL�HNVSUHVL�SRVLWLI��VHGDQJNDQ�SDGD�NHORPSRN�NRQWURO�KDPSLU�VHPXD�EORN�SDUDILQ���� �������� \DQJ� GLQLODL� VHEDJDL� HNVSUHVL�
(�FDGKHULQ�SRVLWLI�GDQ�KDQ\D����������\DQJ�GLQLODL�VHEDJDL�(�FDGKHULQ�QHJDWLI�
8QWXN�PHQJHWDKXL�KXEXQJDQ�SHQXUXQDQ�HNVSUHVL� (�FDGKHULQ� GHQJDQ� EHEHUDSD�JDPEDUDQ�NOLQLV�.1)�VHSHUWL�MHQLV�NHODPLQ��XPXU�� MHQLV� KLVWRSDWRORJL�� XNXUDQ� WXPRU��VWDWXV� .*%�� PHWDVWDVLV� MDXK�� GDQ� VWDGLXP�SHQ\DNLW� GLODNXNDQ� GHQJDQ� DQDOLVLV� x2 test NRPSDUDWLI� NDWHJRULN� WLGDN� EHUSDVDQJDQ��WDEHO����
Tabel 3. Hubungan ekspresi E-cadherin dengan beberapa gambaran klinis KNFEkspresi E-cadherin positif
n (%)Ekspresi E-cadherin negatif
n(%) Nilai p
Jenis kelamin��������/DNL�ODNL��������3HUHPSXDQ
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'DUL� WDEHO� ��� WHUOLKDW� MXPODK� SDVLHQ�.1)� EHUMHQLV� NHODPLQ� ODNL�ODNL� OHELK�EDQ\DN� GDULSDGD� SHUHPSXDQ�� \DLWX� ODNL�ODNL�VHEDQ\DN����RUDQJ���������VHGDQJNDQ�SHUHPSXDQ� ��� RUDQJ� �������� GHQJDQ�UDVLR� ODNL�ODNL� �� SHUHPSXDQ� VHEHVDU� �������Dengan menggunakan x2 test�� WLGDN�WHUGDSDW� SHUEHGDDQ� \DQJ� VLJQLILNDQ� SDGD�MHQLV� NHODPLQ� DQWDUD� NHORPSRN� NDVXV� GDQ�NHORPSRN�NRQWURO�GHQJDQ�QLODL�p �������
8PXU�VXEMHN�SHQHOLWLDQ�WHUPXGD�DGDODK���� WDKXQ� GDQ� \DQJ� WHUWXD� DGDODK� ��� WDKXQ�GHQJDQ�UDWD�UDWD�XPXU����WDKXQ��.HORPSRN�XPXU� WHUEDQ\DN� DGDODK� ������ WDKXQ�VHEDQ\DN����RUDQJ����������'HQJDQ�x2 test WLGDN�GLGDSDWNDQ�SHUEHGDDQ�\DQJ�VLJQLILNDQ�SDGD� XPXU� DQWDUD� NHORPSRN� NDVXV� GHQJDQ�NHORPSRN�NRQWURO��p �������
-HQLV� KLVWRSDWRORJL� \DQJ� WHUEDQ\DN�SDGD� SHQHOLWLDQ� LQL� DGDODK� :+2� WLSH�,,,� �undifferentiated carcinoma��� \DLWX�VHEDQ\DN� ��� SDVLHQ� ��������� VHGDQJNDQ�:+2� WLSH� ,,� �non-keratinizing squamous cell carcinoma�� VHEDQ\DN� �� SDVLHQ� �������GDQ� WLGDN� GLGDSDWNDQ� MHQLV� KLVWRSDWRORJL�
:+2� WLSH� ,� �keratinizing squamous cell carcinoma���+DVLO�x2 test PHQXQMXNNDQ�WLGDN�WHUGDSDW� SHUEHGDDQ� VLJQLILNDQ� SDGD� MHQLV�KLVWRSDWRORJL�DQWDUD�NHGXD�NHORPSRN�GHQJDQ�nilai p �������
%HUGDVDUNDQ�VWDGLXP�SHQ\DNLW�SDGD�WDEHO���� GLGDSDWNDQ� �� SDVLHQ� ������� WHUGLDJQRVLV�.1)� SDGD� VWDGLXP� ,�� �� SDVLHQ� ��������VWDGLXP� ,,�� ��� SDVLHQ� �������� VWDGLXP�,,,�� GDQ� ��� SDVLHQ� �������� VWDGLXP� ,9��.HEDQ\DNDQ�SDVLHQ���������SDGD�SHQHOLWLDQ�LQL�GDWDQJ�NH�SROLNOLQLN�7+7�./�5683�'U��6DUGMLWR� WHUGLDJQRVLV� SDGD� VWDGLXP� ODQMXW��7LGDN� WHUGDSDW� SHUEHGDDQ� \DQJ� VLJQLILNDQ�SDGD� VWDGLXP� SHQ\DNLW� DQWDUD� NHORPSRN�NDVXV�GHQJDQ�NHORPSRN�NRQWURO�GHQJDQ�QLODL�p ������
3HQLODLDQ�HNVSUHVL�(�FDGKHULQ�GLODNXNDQ�ROHK�VHRUDQJ�DKOL�3DWRORJL�$QDWRPL�GHQJDQ�PHODNXNDQ�SHPHULNVDDQ�,+.�PHQJJXQDNDQ�DQWLERGL� (�FDGKHULQ�� HNVSUHVL� (�FDGKHULQ�SRVLWLI� WHUOLKDW� SDGD� PHPEUDQ� PDXSXQ�SDGD� VLWRSODVPD� VHO� WXPRU� \DQJ� EHUZDUQD�NHFRNODWDQ��JDPEDU����
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(C) (D)
Gambar 1.�(NVSUHVL�(�FDGKHULQ�SDGD�MDULQJDQ�ELRSVL�QDVRIDULQJ��$�GDQ�%��HNVSUHVL�(�FDGKHULQ��SDQDK�ZDUQD�PHUDK��WHUOLKDW�SDGD�KDPSLU�VHPXD�VHO�WXPRU��!������PDVLQJ�PDVLQJ�SDGD�SHPEHVDUDQ����[�GDQ����[�&�GDQ�'��SDQDK�ZDUQD�PHUDK��HNVSUHVL�(�FDGKHULQ�WHUOLKDW�KDQ\D�SDGD�VHEDJLDQ�NHFLO�VHO�WXPRU���������PDVLQJ�PDVLQJ�SDGD�SHPEHVDUDQ����[�GDQ����[�
ORLI Vol. 45 No. 1 Tahun 2015 Ekspresi E-cadherin pada metastasis karsinoma nasofaring
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5HUDWD� SHUVHQWDVH� VHO� WXPRU� \DQJ�WHUHNVSUHVL�GLKLWXQJ�GDUL�OLPD�ODSDQJ�SDQGDQJ�EHVDU��SHPEHVDUDQ����[��\DQJ�GLSLOLK�VHFDUD�DFDN� SHU� ���� VHO� WXPRU�� 6XEMHN� SHQHOLWLDQ�GHQJDQ� UHUDWD� SHUVHQWDVH� VHO� WXPRU� \DQJ�
WHUHNVSUHVL� !���� GLNDWHJRULNDQ� VHEDJDL�HNVSUHVL� (�FDGKHULQ� SRVLWLI�� VHGDQJNDQ�\DQJ� ����� GLNDWHJRULNDQ� VHEDJDL� HNVSUHVL�(�FDGKHULQ�QHJDWLI�
Tabel 2. Analisis ekspresi E-cadherin terhadap kelompok kasus dan kontrol
Ekspresi E-cadherin Kasusn (%)
Kontroln(%) Nilai p Odd Ratio
(IK 95%)Negatif ���������� �������� ������ ���������������������Positif �������� ����������
*bermakna p�����
3DGD� WDEHO� ��� HNVSUHVL� (�FDGKHULQ�SRVLWLI� GLWHPXNDQ� SDGD� ��� EORN� SDUDILQ�GDQ� HNVSUHVL� (�FDGKHULQ� QHJDWLI� VHEDQ\DN���� EORN� SDUDILQ� \DQJ� WHUEDJL� PHQMDGL� ���NHORPSRN��3DGD�NHORPSRN�NDVXV��VHEDQ\DN����EORN�SDUDILQ���������\DQJ�GLQLODL�VHEDJDL�HNVSUHVL�QHJDWLI�GDQ���EORN�SDUDILQ���������\DQJ�GLQLODL�HNVSUHVL�SRVLWLI��VHGDQJNDQ�SDGD�NHORPSRN�NRQWURO�KDPSLU�VHPXD�EORN�SDUDILQ���� �������� \DQJ� GLQLODL� VHEDJDL� HNVSUHVL�
(�FDGKHULQ�SRVLWLI�GDQ�KDQ\D����������\DQJ�GLQLODL�VHEDJDL�(�FDGKHULQ�QHJDWLI�
8QWXN�PHQJHWDKXL�KXEXQJDQ�SHQXUXQDQ�HNVSUHVL� (�FDGKHULQ� GHQJDQ� EHEHUDSD�JDPEDUDQ�NOLQLV�.1)�VHSHUWL�MHQLV�NHODPLQ��XPXU�� MHQLV� KLVWRSDWRORJL�� XNXUDQ� WXPRU��VWDWXV� .*%�� PHWDVWDVLV� MDXK�� GDQ� VWDGLXP�SHQ\DNLW� GLODNXNDQ� GHQJDQ� DQDOLVLV� x2 test NRPSDUDWLI� NDWHJRULN� WLGDN� EHUSDVDQJDQ��WDEHO����
Tabel 3. Hubungan ekspresi E-cadherin dengan beberapa gambaran klinis KNFEkspresi E-cadherin positif
n (%)Ekspresi E-cadherin negatif
n(%) Nilai p
Jenis kelamin��������/DNL�ODNL��������3HUHPSXDQ
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/03�� PHUXSDNDQ� SURWHLQ� PHPEUDQ�\DQJ� WHUGLUL� GDUL� GRPDLQ� SHQGHN� 1+2�terminal��HQDP�GRPDLQ� WUDQVPHPEUDQ��GDQ�200 asam amino domain COOH-terminal��.HEDQ\DNDQ�signal�/03��GLEDWDVL�COOH-Terminal Activation Region� �&7$5��� \DQJ�NHPXGLDQ� GLEDJL� ODJL�PHQMDGL� GXD� GRPDLQ�XWDPD�� &7$5�� GDQ� &7$5��� &7$5��berhubungan dengan Tumor Necrosis Factor �71)��Receptor Associated Factor Proteins �75$)��� VHGDQJNDQ� &7$5�� EHULQWHUDNVL�GHQJDQ� 71)� Receptor Associated Death Domain Protein� �75$''��� &7$5�� GDQ�&7$5�� PHPHGLDVL� MDOXU� 1)ț%� GDQ� S���Mitogen Activated Protein Kinase�0$3.���3DGD� &7$5��� NKXVXVQ\D� DVDP� DPLQR� ��WHUDNKLU� �<<'��� PHUXSDNDQ� ORNDVL� NXQFL�/03��PHPLFX�DNWLYLWDV�$3���PHODOXL�MDOXU�F�-XQL�1+��WHUPLQDO�NLQDVH��-1.����
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Ekspresi E-cadherin pada metastasis karsinoma nasofaringORLI Vol. 45 No. 1 Tahun 2015
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ORLI Vol. 45 No. 1 Tahun 2015 Ekspresi E-cadherin pada metastasis karsinoma nasofaring
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