{\rtf1{\fonttbl{\f2 Times New Roman;}{\f3 Times New Roman Bold;}{\f4 Times New Roman Bold Italic;}{\f5 Times New Roman;}{\f6 Times New Roman;}{\f7 Arial;}{\f8 Times New Roman Italic;}{\f9 Times New Roman Bold;}{\f10 Times New Roman Bold;}{\f11 Times New Roman;}{\f1000000 Times New Roman;}}{\colortbl;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;\red0\green0\blue0;}\viewkind1\viewscale100\margl0\margr0\margt0\margb0\deftab80\dntblnsbdb\expshrtn\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg1}{\bkmkend Pg1}\par\pard\ql \li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb0\sl-276\slmult0 \par\pard\ql\li5899\sb79\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf2\f3\fs24 BAB 2 \par\pard\ql \li5011\sb0\sl-276\slmult0 \par\pard\ql\li5011\sb228\sl-276\slmult0 \up0 \expndtw-5\charscalex100 TINJAUAN PUSTAKA \par\pard\ql \li2318\sb0\sl-276\slmult0 \par\pard\ql\li2318\sb248\sl-276\slmult0 \up0 \expndtw-5\charscalex100 \ul0\nosupersub\cf3\f4\fs24 2.1. Kanker Payudara \par\pard\qj \li2265\ri1495\sb156\sl-552\slmult0\fi657 \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Kanker payudara merupakan salah satu penyakit kanker tertua pada \line \up0 \expndtw-3\charscalex100 manusia. Penyakit kanker payudara telah dikenali sejak jaman mesir kuno 1600 \line \up0 \expndtw0\charscalex100 SM, walaupun pada saat itu belum ada definisi mengenai kanker. Edwin Smith \line \up0 \expndtw-2\charscalex100 Papyrus melaporkan ada 8 kasus tumor yang disertai ulkus pada daerah payudara \line \up0 \expndtw0\charscalex100 yang diterapi dengan cara dibakar dengan api. Pada abad 17 seorang ahli bedah \line \up0 \expndtw0\charscalex100 Perancis Jean Louis Petit \up0 \expndtw0\charscalex102 (1674 - 1750) menemukan kasus kanker payudara \par\pard\qj \li2265\ri1502\sb2\sl-560\slmult0 \up0 \expndtw0\charscalex100 yang disertai pembesaran limfonodi didaerah aksila. Kemudian ahli bedah dari \line \up0 \expndtw-2\charscalex100 Skotlandia Benjamin Bell \up0 \expndtw-3\charscalex100 (1749 \up0 \expndtw-3\charscalex100 -\up0 \expndtw-2\charscalex100 1806) melakukan operasi pengangkatan \par\pard\qj \li2265\ri1502\sb0\sl-550\slmult0 \up0 \expndtw0\charscalex103 kelenjar payudara beserta otot-otot dada dan limfonodi aksila, baru kemudian \up0 \expndtw0\charscalex100 dipopulerkan oleh William Stewart Halsted (1882) melakukan Halsted Radikal \up0 \expndtw-5\charscalex100 Mastectomy dan prosedur ini tetap populer sampai tahun 1970.\ul0\super\cf5\f6\fs23 3,10,16 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb190\sl-276\slmult0 \up0 \expndtw-5\charscalex100 \ul0\nosupersub\cf2\f3\fs24 2.1.1. Etiologi dan patogenesis \par\pard\ql \li2870\sb0\sl-276\slmult0 \par\pard\ql\li2870\sb68\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Ada 3 pengaruh penting pada kanker payudara : \par\pard\ql \li2870\sb264\sl-276\slmult0 \up0 \expndtw-4\charscalex100 1. Faktor genetik \par\pard\qj \li3168\ri1496\sb56\sl-553\slmult0 \up0 \expndtw0\charscalex101 Faktor genetik berpengaruh dalam peningkatan terjadinya kanker \line \up0 \expndtw0\charscalex101 payudara. Pada percobaan tikus dengan galur sensitif kanker, melalui \line \up0 \expndtw0\charscalex100 persilangan genetik didapatkan tikus yang terkena kanker. Ada faktor \line \up0 \expndtw-4\charscalex100 turunan pada suatu keluarga yang terkena kanker payudara. Kelainan ini \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb104\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 23 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg2}{\bkmkend Pg2}\par\pard\ql \li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb0\sl-276\slmult0 \par\pard\ql\li3168\sb79\sl-276\slmult0\tx8178 \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf4\f5\fs24 diketahui terletak dilokus kecil di kromosom \tab \up0 \expndtw0\charscalex100 17q21 pada kanker \par\pard\ql \li3168\sb0\sl-264\slmult0 \par\pard\ql\li3168\sb10\sl-264\slmult0 \up0 \expndtw-4\charscalex100 payudara yang timbul saat usia muda.\ul0\super\cf5\f6\fs23 17,18 \par\pard\ql \li2807\sb0\sl-276\slmult0 \par\pard\ql\li2807\sb11\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 2. Hormon \par\pard\qj \li3167\ri1495\sb36\sl-552\slmult0 \up0 \expndtw-2\charscalex100 Kelebihan hormon estrogen endogen atau lebih tepatnya terjadi ketidak \line \up0 \expndtw-4\charscalex100 seimbangan hormon terlihat sangat jelas pada kanker payudara. Banyak \line \up0 \expndtw-3\charscalex100 faktor resiko yang dapat disebutkan seperti masa reproduksi yang lama, \line \up0 \expndtw-4\charscalex100 nulipara, dan usia tua saat mempunyai anak pertama akan meningkatkan \line \up0 \expndtw-4\charscalex100 estrogen pada siklus menstruasi. Wanita pasca menopause dengan tumor \line \up0 \expndtw0\charscalex100 ovarium fungsional dapat terkena kanker payudara karena adanya \line \up0 \expndtw-1\charscalex100 hormon estrogen berlebihan. Suatu penelitian menyebutkan bahwa \line \up0 \expndtw0\charscalex103 kelebihan jumlah estrogen di urin, frekwensi ovulasi, dan umur saat \line \up0 \expndtw0\charscalex101 menstruasi dihubungkan dengan meningkatnya resiko terkena kanker \line \up0 \expndtw0\charscalex101 payudara.\ul0\super\cf5\f6\fs23 19,20\ul0\nosupersub\cf4\f5\fs24 Epitel payudara normal memiliki reseptor estrogen dan \line \up0 \expndtw0\charscalex104 progesteron. Kedua reseptor ditemukan pada sebagian besar kanker \line \up0 \expndtw-2\charscalex100 payudara. Berbagai bentuk growth promoters \up0 \expndtw-4\charscalex100 (transforming growth \par\pard\qj \li3167\ri1495\sb8\sl-552\slmult0 \up0 \expndtw-2\charscalex100 factor-alpha/epitehlial growth factor, platelet-derived growth factor), \line \up0 \expndtw0\charscalex100 fibroblast growth factor dan growth inhibitor disekresi oleh sel kanker \line \up0 \expndtw-1\charscalex100 payudara manusia. Banyak penelitian menyatakan bahwa growth \line \up0 \expndtw-1\charscalex100 promoters terlibat dalam mekanisme autokrin dari tumor. Produksi GF \line \up0 \expndtw0\charscalex103 tergantung pada hormon estrogen, sehingga interaksi antara hormon \line \up0 \expndtw0\charscalex102 disirkulasi, reseptor hormon pada sel kanker dan \up0 \expndtw0\charscalex100 GF autokrin \par\pard\ql \li3167\sb226\sl-264\slmult0 \up0 \expndtw-4\charscalex100 merangsang sel tumor menjadi lebih progresif.\ul0\super\cf5\f6\fs23 17,21 \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb55\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 24 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg3}{\bkmkend Pg3}\par\pard\ql \li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb79\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 3. Faktor lingkungan dan gaya hidup \par\pard\ql \li3168\sb264\sl-276\slmult0\tx10141 \up0 \expndtw0\charscalex100 Pengaruh lingkungan diduga karena berbagai faktor antara lain \tab \up0 \expndtw-3\charscalex100 : \par\pard\qj \li3168\ri1503\sb66\sl-540\slmult0 \up0 \expndtw0\charscalex107 alkohol, diet tinggi lemak, dan infeksi virus. Hal tersebut mungkin \line \up0 \expndtw-3\charscalex100 mempengaruhi onkogen dan gen supresi tumor dari kanker payudara.\ul0\super\cf5\f6\fs23 17,18 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb203\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf2\f3\fs24 2.1.2. Klasifikasi \par\pard\qj \li2985\ri1504\sb126\sl-540\slmult0 \up0 \expndtw-1\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Berdasarkan gambaran histologis, WHO membuat klasifikasi kanker \up0 \expndtw-4\charscalex100 payudara sebagai berikut.\ul0\super\cf5\f6\fs23 21,22,20 \par\pard\ql \li2985\sb0\sl-276\slmult0 \par\pard\ql\li2985\sb83\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 a.\ul0\nosupersub\cf6\f7\fs24 \ul0\nosupersub\cf4\f5\fs24 Kanker Payudara Non Invasif \par\pard\ql \li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb8\sl-276\slmult0 \up0 \expndtw-4\charscalex100 1.\ul0\nosupersub\cf6\f7\fs24 \ul0\nosupersub\cf4\f5\fs24 Karsinoma intraduktus non invasif \par\pard\qj \li3796\ri1495\sb38\sl-550\slmult0 \up0 \expndtw-1\charscalex100 Karsinoma intraduktus adalah karsinoma yang mengenai duktus \line \up0 \expndtw-1\charscalex100 disertai infiltrasi jaringan stroma sekitar. Terdapat 5 subtipe dari \line \up0 \expndtw0\charscalex101 karsinoma intraduktus, yaitu \up0 \expndtw-3\charscalex100 : \up0 \expndtw-1\charscalex100 komedokarsinoma, solid, \par\pard\qj \li3796\ri1489\sb9\sl-552\slmult0\fi0 \up0 \expndtw-1\charscalex100 kribriformis, papiler, dan mikrokapiler. Komedokarsinoma \line \up0 \expndtw0\charscalex102 ditandai dengan sel-sel yang berproliferasi cepat dan memiliki \line \up0 \expndtw0\charscalex103 derajat keganasan tinggi. Karsinoma jenis ini dapat meluas ke \line \up0 \expndtw-1\charscalex100 duktus ekskretorius utama, kemudian menginfiltrasi \ul0\nosupersub\cf7\f8\fs24 papilla\ul0\nosupersub\cf4\f5\fs24 dan \line \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf7\f8\fs24 areola,\ul0\nosupersub\cf4\f5\fs24 sehingga dapat menyebabkan penyakit Paget pada \line \up0 \expndtw-3\charscalex100 payudara. \par\pard\ql \li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb80\sl-276\slmult0 \up0 \expndtw-3\charscalex100 2.\ul0\nosupersub\cf6\f7\fs24 \ul0\nosupersub\cf4\f5\fs24 Karsinoma lobular insitu \par\pard\qj \li3705\ri1497\sb30\sl-560\slmult0 \up0 \expndtw0\charscalex102 Karsinoma ini ditandai dengan pelebaran satu atau lebih duktus \line \up0 \expndtw-4\charscalex100 terminal dan atau tubulus, tanpa disertai infiltrasi ke dalam stroma. \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb3\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 25 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg4}{\bkmkend Pg4}\par\pard\qj \li3705\sb0\sl-540\slmult0 \par\pard\qj\li3705\sb0\sl-540\slmult0 \par\pard\qj\li3705\sb0\sl-540\slmult0 \par\pard\qj\li3705\ri1494\sb173\sl-540\slmult0 \up0 \expndtw0\charscalex108 \ul0\nosupersub\cf4\f5\fs24 Sel-sel berukuran lebih besar dari normal, inti bulat kecil dan \up0 \expndtw-3\charscalex100 jarang disertai mitosis. \par\pard\li2985\sb0\sl-276\slmult0\par\pard\li2985\sb90\sl-276\slmult0\fi0\tx3345 \up0 \expndtw-3\charscalex100 b.\tab \up0 \expndtw-3\charscalex100 Kanker Payudara Invasif\par\pard\li2985\sb276\sl-276\slmult0\fi360\tx3705 \up0 \expndtw-3\charscalex100 1.\tab \up0 \expndtw-3\charscalex100 Karsinoma duktus invasif\par\pard\qj \li3705\ri1496\sb37\sl-553\slmult0 \up0 \expndtw0\charscalex100 Karsinoma jenis ini merupakan bentuk paling umum dari kanker \line \up0 \expndtw0\charscalex102 payudara. Karsinoma duktus infiltratif merupakan 65-80% dari \line \up0 \expndtw-4\charscalex100 karsinoma payudara. Secara histologis, jaringan ikat padat tersebar \line \up0 \expndtw-5\charscalex100 berbentuk sarang. Sel berbentuk bulat sampai poligonal, bentuk inti \line \up0 \expndtw-5\charscalex100 kecil dengan sedikit gambaran mitosis. Pada tepi tumor, tampak sel \line \up0 \expndtw0\charscalex102 kanker mengadakan infiltrasi ke jaringan sekitar seperti sarang, \line \up0 \expndtw0\charscalex103 kawat atau seperti kelenjar. Jenis ini disebut juga sebagai \par\pard\qj \li3705\ri1494\sb0\sl-550\slmult0 \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf7\f8\fs24 infiltrating ductus carcinoma not otherrwiser spercifierd (NOS), \line \up0 \expndtw0\charscalex100 scirrhous carcinoma, infiltrating carcinoma, atau carcinoma \line \up0 \expndtw-3\charscalex100 simplex. \par\pard\ql \li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb71\sl-276\slmult0\tx3705 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 2. \tab \up0 \expndtw-3\charscalex100 Karsinoma lobular invasif \par\pard\qj \li3705\ri1498\sb56\sl-552\slmult0 \up0 \expndtw-3\charscalex100 Jenis ini merupakan karsinoma infiltratif yang tersusun atas sel-sel \up0 \expndtw-3\charscalex100 berukuran kecil dan seragam dengan sedikit pleimorfisme. \up0 \expndtw-2\charscalex100 Karsinoma lobular invasive biasanya memiliki tingkat mitosis \up0 \expndtw-3\charscalex100 rendah. Sel infiltratif biasanya tersusun konsentris disekitar duktus \up0 \expndtw0\charscalex100 berbentuk seperti target. Sel tumor dapat berbentuk \ul0\nosupersub\cf7\f8\fs24 signet-ring\ul0\nosupersub\cf4\f5\fs24 , \up0 \expndtw-5\charscalex100 \ul0\nosupersub\cf7\f8\fs24 tubuloalveolar\ul0\nosupersub\cf4\f5\fs24 , atau \ul0\nosupersub\cf7\f8\fs24 solid. \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb74\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 26 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg5}{\bkmkend Pg5}\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb82\sl-276\slmult0\fi0\tx3705 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 3.\tab \up0 \expndtw-3\charscalex100 Karsinoma musinosum\par\pard\qj \li3705\ri1504\sb35\sl-550\slmult0 \up0 \expndtw0\charscalex100 Pada karsinoma musinosum ini didapatkan sejumlah besar mucus \line \up0 \expndtw0\charscalex101 intra dan ekstraseluler yang dapat dilihat secara makroskopis \line \up0 \expndtw-1\charscalex100 maupun mikroskopis. Secara histologis, terdapat \up0 \expndtw0\charscalex101 3 bentuk sel \par\pard\qj \li3705\ri1498\sb9\sl-552\slmult0 \up0 \expndtw-2\charscalex100 kanker. Bentuk pertama, sel tampak seperti pulau-pulau kecil yang \up0 \expndtw0\charscalex106 mengambang dalam cairan musin basofilik. Bentuk kedua, sel \up0 \expndtw0\charscalex101 tumbuh dalam susunan kelenjar berbatas jelas dan lumennya \up0 \expndtw0\charscalex103 mengandung musin. Bentuk ketiga terdiri dari susunan jaringan \up0 \expndtw0\charscalex106 yang tidak teratur berisi sel tumor tanpa diferensiasi, sebagian \up0 \expndtw-3\charscalex100 besar sel berbentuk \ul0\nosupersub\cf7\f8\fs24 signet-ring\ul0\nosupersub\cf4\f5\fs24 . \par\pard\ql \li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb80\sl-276\slmult0\tx3705 \up0 \expndtw-3\charscalex100 4. \tab \up0 \expndtw-3\charscalex100 Karsinoma meduler \par\pard\qj \li3705\ri1495\sb38\sl-550\slmult0 \up0 \expndtw0\charscalex103 Sel berukuran besar berbentuk polygonal/lonjong dengan batas \line \up0 \expndtw0\charscalex106 sitoplasma tidak jelas. Diferensiasi dari jenis ini buruk, tetapi \line \up0 \expndtw0\charscalex100 memiliki prognosis lebih baik daripada karsinoma \up0 \expndtw-4\charscalex100 duktus \par\pard\qj \li3705\ri1490\sb10\sl-550\slmult0 \up0 \expndtw0\charscalex101 infiltratif. Biasanya terdapat infiltrasi limfosit yang nyata dalam \line \up0 \expndtw-3\charscalex100 jumlah sedang diantara sel kanker, terutama dibagian tepi jaringan \line \up0 \expndtw-3\charscalex100 kanker. \par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb88\sl-276\slmult0\fi0\tx3705 \up0 \expndtw-3\charscalex100 5.\tab \up0 \expndtw-3\charscalex100 Karsinoma papiler invasif\par\pard\li3345\sb276\sl-276\slmult0\fi360 \up0 \expndtw-3\charscalex100 Komponen invasif dari jenis karsinoma ini berbentuk papiler.\par\pard\li3345\sb0\sl-276\slmult0\par\pard\li3345\sb120\sl-276\slmult0\fi0\tx3705 \up0 \expndtw-3\charscalex100 6.\tab \up0 \expndtw-3\charscalex100 Karsinoma tubuler\par\pard\qj \li3705\ri1496\sb47\sl-550\slmult0 \up0 \expndtw0\charscalex104 Pada karsinoma tubuler, bentuk sel teratur dan tersusun secara \up0 \expndtw-4\charscalex100 tubuler selapis, dikelilingi oleh stroma fibrous. Jenis ini merupakan \up0 \expndtw-4\charscalex100 karsinoma dengan diferensiasi tinggi. \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb5\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 27 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg6}{\bkmkend Pg6}\par\pard\ql \li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb79\sl-276\slmult0 \up0 \expndtw-1\charscalex100 \ul0\nosupersub\cf4\f5\fs24 7.\ul0\nosupersub\cf6\f7\fs24 \ul0\nosupersub\cf4\f5\fs24 Karsinoma adenokistik \par\pard\qj \li3705\ri1494\sb38\sl-550\slmult0 \up0 \expndtw0\charscalex104 Jenis ini merupakan karsinoma invasif dengan karakteristik sel \line \up0 \expndtw0\charscalex104 yang berbentuk kribriformis. Sangat jarang ditemukan pada \line \up0 \expndtw-4\charscalex100 payudara. \par\pard\ql \li3345\sb0\sl-276\slmult0 \par\pard\ql\li3345\sb81\sl-276\slmult0 \up0 \expndtw0\charscalex100 8.\ul0\nosupersub\cf6\f7\fs24 \ul0\nosupersub\cf4\f5\fs24 Karsinoma apokrin \par\pard\qj \li3705\ri1495\sb61\sl-546\slmult0 \up0 \expndtw0\charscalex101 Karsinoma ini didominasi dengan sel yang memiliki sitoplasma \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf7\f8\fs24 eosinofili\ul0\nosupersub\cf4\f5\fs24 k, sehingga menyerupai sel apokrin yang mengalami \up0 \expndtw0\charscalex100 metaplasia. Bentuk karsinoma apokrin dapat ditemukan juga pada \up0 \expndtw-3\charscalex100 jenis karsinoma payudara yang lain. \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb90\sl-276\slmult0 \up0 \expndtw-5\charscalex100 \ul0\nosupersub\cf2\f3\fs24 2.2. \ul0\nosupersub\cf3\f4\fs24 Immunosurveillance kanker \par\pard\qj \li2265\ri1494\sb36\sl-552\slmult0\fi720 \up0 \expndtw0\charscalex101 \ul0\nosupersub\cf4\f5\fs24 Mekanisme yang digunakan oleh tubuh untuk bereaksi melawan setiap \line \up0 \expndtw-1\charscalex100 antigen yang diekspresikan oleh neoplasma disebut\ul0\nosupersub\cf7\f8\fs24 Immunosurveillance\ul0\nosupersub\cf4\f5\fs24 . Fungsi \line \up0 \expndtw-1\charscalex100 primer dari sistem imun adalah untuk mengenal dan mendegradasi antigen asing \line \up0 \expndtw0\charscalex100 (nonself) yang timbul dalam tubuh. Dalam \ul0\nosupersub\cf7\f8\fs24 immunosurveillance\ul0\nosupersub\cf4\f5\fs24 , sel mutan \line \up0 \expndtw0\charscalex105 dianggap akan mengekspresikan satu atau lebih antigen yang dapat dikenal \line \up0 \expndtw0\charscalex104 sebagai \ul0\nosupersub\cf7\f8\fs24 nonself\ul0\nosupersub\cf4\f5\fs24 . Sel mutan dianggap sering timbul dalam tubuh manusia dan \line \up0 \expndtw0\charscalex103 tetapi secara cepat dihancurkan oleh mekanisme imunologis. Pada tikus yang \line \up0 \expndtw-2\charscalex100 kehilangan imunitas seluler dan terpapar agen onkogenik akan lebih cepat timbul \line \up0 \expndtw0\charscalex100 tumor. Ini dianggap merupakan bukti mekanisme \ul0\nosupersub\cf7\f8\fs24 immunosurveillance\ul0\nosupersub\cf4\f5\fs24 . Sel NK\ul0\nosupersub\cf7\f8\fs24 , \line \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf4\f5\fs24 CTL dan makrofag\ul0\nosupersub\cf7\f8\fs24 \ul0\nosupersub\cf4\f5\fs24 ternyata paling berperan dalam \ul0\nosupersub\cf7\f8\fs24 immunosurveillance \ul0\nosupersub\cf4\f5\fs24 tumor, \line \up0 \expndtw0\charscalex105 setelah mengenal sel kanker sebagai sel asing, ketiga sel imun tersebut akan \line \up0 \expndtw0\charscalex102 menghancurkan sel kanker. Sel CTL dan sel NK melakukan cara sitotoksisitas \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb124\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 28 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg7}{\bkmkend Pg7}\par\pard\qj \li2265\sb0\sl-540\slmult0 \par\pard\qj\li2265\sb0\sl-540\slmult0 \par\pard\qj\li2265\sb0\sl-540\slmult0 \par\pard\qj\li2265\ri1516\sb173\sl-540\slmult0 \up0 \expndtw0\charscalex104 \ul0\nosupersub\cf4\f5\fs24 yang sama yaitu dengan mengeluarkan perforin, sedangkan makrofag \up0 \expndtw-2\charscalex100 menggunakan cara fagositosis.\ul0\super\cf5\f6\fs23 9,7,8,23 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb203\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf3\f4\fs24 2.3. Respon Imunologik Terhadap Sel Kanker \par\pard\qj \li2265\ri1501\sb117\sl-551\slmult0\fi719 \up0 \expndtw-1\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Sel kanker dikenal oleh tubuh sebagai benda asing, sehingga mekanisme \line \up0 \expndtw-1\charscalex100 imunologi tubuh akan bereaksi secara humoral maupun seluler. Tubuh \line \up0 \expndtw-2\charscalex100 mempunyai kemampuan \ul0\nosupersub\cf7\f8\fs24 immunosurveillance\ul0\nosupersub\cf3\f4\fs24 \ul0\nosupersub\cf4\f5\fs24 terhadap semua sel kanker maupun \line \up0 \expndtw0\charscalex100 sel yang bermutasi untuk mencegah perkembangan sel kanker tersebut, namun \line \up0 \expndtw0\charscalex100 terkadang terjadi \ul0\nosupersub\cf7\f8\fs24 immunological escape\ul0\nosupersub\cf4\f5\fs24 yaitu sel kanker luput dari pengawasan \line \up0 \expndtw-3\charscalex100 sistem imun, sehingga terjadilah kanker. Penderita kanker sendiri juga mengalami \line \up0 \expndtw0\charscalex102 supresi imun dan modalitas terapi kanker juga mempengaruhi sistem imun itu \line \up0 \expndtw-1\charscalex100 sendiri. Respon sistem imun terhadap sel kanker dapat dibagi dua yaitu humoral \par\pard\ql \li2265\sb0\sl-241\slmult0 \par\pard\ql\li2265\sb5\sl-241\slmult0 \up0 \expndtw-2\charscalex100 dan seluler. \ul0\super\cf5\f6\fs23 7-9,23,24 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb255\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf2\f3\fs24 2.3.1. Peranan sistem imun seluler terhadap sel kanker \par\pard\qj \li2265\ri1499\sb57\sl-551\slmult0\fi719 \up0 \expndtw-2\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Pada pemeriksaan patologi-anatomi tumor, sering ditemukan infiltrat sel\up0 \expndtw0\charscalex100 sel yang terdiri atas sel fagosit mononuklear, limfosit, sedikit sel plasma dan sel \up0 \expndtw-2\charscalex100 mastosit. Meskipun pada beberapa neoplasma, infiltrasi sel mononuclear \up0 \expndtw0\charscalex100 merupakan indikator untuk prognosis yang baik, pada umumnya tidak ada \up0 \expndtw0\charscalex100 hubungan antara infiltrasi sel dengan prognosis. Sistem imun yang nonspesifik \up0 \expndtw-1\charscalex100 dapat langsung menghancurkan sel tumor tanpa sensitisasi polimorfonuklear, sel \up0 \expndtw-1\charscalex100 NK. Aktivasi sel T melibatkan sel Th dan CTL. Sel Th penting pada pengerahan \up0 \expndtw-4\charscalex100 dan aktivasi makrofag dan sel NK.\ul0\super\cf5\f6\fs23 8,23,24 \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb5\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 29 \par\pard\sect\sectd\fs24\paperw11900\paperh16840{\shp{\*\shpinst\shpleft6460\shptop7280\shpright10220\shpbottom7520\shpwr3\shpfblwtxt0\shpbxpage\shpbypage\shpz154\shplid7{\sp{\sn shapeType}{\sv 75}}{\sp{\sn fBehindDocument}{\sv 1}}{\sp{\sn pib}{\sv 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Pg8}{\bkmkend Pg8}\par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb79\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf2\f3\fs24 a) Sitotoksitas melalui sel T \par\pard\qj \li2265\ri1500\sb36\sl-553\slmult0\fi719 \up0 \expndtw0\charscalex103 \ul0\nosupersub\cf4\f5\fs24 Subpopulasi limfosit T, limfosit T-helper dan T-sitotoksik sama-sama \line \up0 \expndtw0\charscalex104 berperan dalam mengeliminasi antigen tumor. Sel yang mengandung antigen \line \up0 \expndtw0\charscalex102 tumor akan mengekspresikan antigennya bersama molekul MHC kelas I yang \line \up0 \expndtw-2\charscalex100 kemudian membentuk komplek melalui T-cell Receptor \up0 \expndtw0\charscalex100 (TCR) dari sel T-\par\pard\qj \li2265\ri1500\sb13\sl-546\slmult0 \up0 \expndtw-2\charscalex100 sitotoksik (CD8\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 ), mengaktifasi sel T-sitotoksik untuk menghancurkan sel tumor \line \up0 \expndtw-1\charscalex100 tersebut. Sebagian kecil sel tumor juga mengekspresikan antigen tumor bersama \line \up0 \expndtw-2\charscalex100 molekul MHC kelas II, sehingga dapat dikenali dan membentuk komplek dengan \line \up0 \expndtw-4\charscalex100 limfosit T-helper (Sel T CD4\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 ) dan mengaktivasi sel T-helper terutama subset Th1 \par\pard\li2265\sb249\sl-276\slmult0\fi0\tx6014 \up0 \expndtw-1\charscalex100 untuk mense\tab \up0 \expndtw-1\charscalex100 TNF\par\pard\qj \li2265\ri1497\sb50\sl-546\slmult0 \up0 \expndtw0\charscalex106 sel tumor untuk lebih banyak lagi mengekspresikan molekul MHC kelas I, \line \up0 \expndtw-1\charscalex100 sehingga akan lebih mengoptimalkan sitotoksisitas dari sel T-sitotoksik (CD8\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 ). \line \up0 \expndtw-1\charscalex100 Konsep ini diaplikasikan dalam pengobatan tumor menggunakan \ul0\nosupersub\cf7\f8\fs24 Tumor \line \up0 \expndtw-2\charscalex100 Infiltrating Lymphocytes \up0 \expndtw0\charscalex104 \ul0\nosupersub\cf4\f5\fs24 (TIL), yaitu sel-sel mononuklear yang berinfiltrasi \par\pard\qj \li2265\ri1504\sb3\sl-560\slmult0 \up0 \expndtw0\charscalex105 menuju ke sekitar jaringan tumor padat karena adannya reaksi inflamasi, sel \up0 \expndtw-4\charscalex100 tersebut diperbanyak secara kultur in vitro dengan penambahan IL-2.\ul0\super\cf5\f6\fs23 24-27 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb179\sl-276\slmult0 \up0 \expndtw-5\charscalex100 \ul0\nosupersub\cf2\f3\fs24 b) Sel \ul0\nosupersub\cf3\f4\fs24 Natural Killer \par\pard\qj \li2265\ri1499\sb56\sl-552\slmult0\fi715 \up0 \expndtw0\charscalex102 \ul0\nosupersub\cf4\f5\fs24 Sel NK berukuran sedikit lebih besar dari pada sel limfosit kecil, \line \up0 \expndtw0\charscalex104 berjumlah 10-15% limfosit darah perifer. Secara morfologi sel NK termasuk \line \up0 \expndtw0\charscalex106 dalam populasi \ul0\nosupersub\cf7\f8\fs24 Large Granular Lympocyte \ul0\nosupersub\cf4\f5\fs24 (LGL). Granular Ini terdiri atas \line \up0 \expndtw-1\charscalex100 granula sitotoksik dari sitoplasma yang dikeluarkan saat aktivitas sitotoksik. Sel \line \up0 \expndtw0\charscalex103 NK dapat berperan dalam respon imun spesifik maupun non spesifik. Sel NK \line \up0 \expndtw-3\charscalex100 merupakan sel efektor terhadap sitotoksisitas spontan berbagai jenis sasaran, tidak \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb124\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 30 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg9}{\bkmkend Pg9}\par\pard\qj \li2265\sb0\sl-550\slmult0 \par\pard\qj\li2265\sb0\sl-550\slmult0 \par\pard\qj\li2265\sb0\sl-550\slmult0 \par\pard\qj\li2265\ri1499\sb135\sl-550\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 memiliki sifat klasik dari makrofag, granulosit maupun CTL dan sitotoksisitasnya \line \up0 \expndtw-2\charscalex100 tidak tergantung pada MHC. Mekanisme lisis yang digunakan sama dengan yang \line \up0 \expndtw0\charscalex104 dilakukan oleh CTL yaitu dengan mengeluarkan perforin dan granzym yang \line \up0 \expndtw-1\charscalex100 menyebabkan sel kanker lisis, mengeluarkan IFN sehingga meningkatkan kerja \line \up0 \expndtw-3\charscalex100 fagositosis makrofag, melakukan \ul0\nosupersub\cf7\f8\fs24 recognition\ul0\nosupersub\cf4\f5\fs24 dengan sel kanker dengan perantara \line \up0 \expndtw0\charscalex106 FAS Ligan terhadap sel kanker yang telah diopsonisasi sehingga sel kanker \line \up0 \expndtw-4\charscalex100 diprogram apoptosis.\ul0\super\cf5\f6\fs23 26,27 \par\pard\qj \li2265\ri1496\sb10\sl-550\slmult0\fi715 \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Sel NK tidak mengeluarkan TCR dan merupakan CD3 negatif. Sebagai \line \up0 \expndtw-3\charscalex100 gantinya sel NK mengeluarkan 2 tipe reseptor yang memperkuat kemampuannya \line \up0 \expndtw0\charscalex100 membunuh sel kanker dan sel yang terinfeksi virus, yaitu reseptor pengaktivasi \line \up0 \expndtw-2\charscalex100 yang masih mengenali molekul yang dilingkupi oleh penyakit pada sel target dan \line \up0 \expndtw-4\charscalex100 \ul0\nosupersub\cf7\f8\fs24 Killer Inhibitor Receptor \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf4\f5\fs24 (KIR) yang menghambat sitolisis NK melalui \par\pard\qj \li2265\ri1496\sb10\sl-550\slmult0 \up0 \expndtw0\charscalex102 pengenalan terhadap molekul MHC I-nya sendiri. Sel NK tidak melisiskan sel \line \up0 \expndtw-2\charscalex100 berinti yang sehat karena semuanya mengeluarkan MHC I. Jika infeksi virus dan \line \up0 \expndtw0\charscalex100 atau perubahan neoplastik mengurangi pengeluaran MHC I normal, sinyal KIR \line \up0 \expndtw0\charscalex104 akan terganggu dan terjadilah lisis. Disisi lain sel NK juga mengekspresikan \line \up0 \expndtw-4\charscalex100 CD56 yaitu suatu molekul yang mampu mempromosikan adhesi intraseluler.\ul0\super\cf5\f6\fs23 9,27 \par\pard\ql \li2980\sb237\sl-276\slmult0 \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Sel NK mempunyai reseptor untuk bagian tetap \par\pard\qj \li2265\ri1495\sb34\sl-555\slmult0\fi0 \up0 \expndtw0\charscalex100 dari IgG yang menjadikannya sitotoksisitas tergantung \ul0\nosupersub\cf7\f8\fs24 antibody dependent \line \up0 \expndtw-2\charscalex100 sellular cytotoxicity \ul0\nosupersub\cf4\f5\fs24 (ADCC). Antigen yang diopsonisasi oleh IgG akan dikenali \line \up0 \expndtw0\charscalex100 oleh sel NK untuk dilisiskan. Aktivitas ADCC ini penting untuk efek terapeutik \line \up0 \expndtw-1\charscalex100 optimal dari antibodi monoklonal tumor spesifik. Pada penelitian-penelitian \line \up0 \expndtw-1\charscalex100 terakhir mengungkapkan bahwa pengikatan sel NK terhadap sel sasaran dapat \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb134\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 31 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg10}{\bkmkend Pg10}\par\pard\qj \li2265\sb0\sl-540\slmult0 \par\pard\qj\li2265\sb0\sl-540\slmult0 \par\pard\qj\li2265\sb0\sl-540\slmult0 \par\pard\qj\li2265\ri1506\sb173\sl-540\slmult0 \up0 \expndtw0\charscalex100 \ul0\nosupersub\cf4\f5\fs24 terjadi melalui sel reseptor khusus yang berbeda dengan Fc yaitu reseptor NKR\up0 \expndtw-3\charscalex100 PI, yang mengikat molekul semacam lektin.\ul0\super\cf5\f6\fs23 20,27 \par\pard\li2985\sb246\sl-276\slmult0\fi0\tx7834 \up0 \expndtw0\charscalex104 \ul0\nosupersub\cf4\f5\fs24 Kemampuan sel ditingkatkan oleh IFN\tab \up0 \expndtw0\charscalex104 , IL-2, IL-12, sehingga\par\pard\qj \li2265\ri1497\sb29\sl-553\slmult0 \up0 \expndtw0\charscalex103 peran anti tumor sel NK bergantung pada rangsangan yang terjadi secara \up0 \expndtw0\charscalex104 bersamaan pada sel T dan makrofag yang memproduksi sitokin tersebut. IFN \up0 \expndtw0\charscalex106 mengubah sel pre-NK menjadi sel NK. Aktivitas sel NK sering dihubungkan \up0 \expndtw0\charscalex105 dengan prognosis karena sel NK mempunyai peran penting dalam mencegah \up0 \expndtw0\charscalex103 metastasis dengan mengeliminasi sel tumor dalam sirkulasi. Hal ini dibuktikan \up0 \expndtw0\charscalex100 dengan adanya penelitian yang mengungkapkan bahwa 90%-99% sel tumor yang \up0 \expndtw-3\charscalex100 dimasukkkan intravena akan hilang dalam 24 jam.\ul0\super\cf5\f6\fs23 26,27 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb200\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf2\f3\fs24 c) Sitotoksisitas melalui makrofag \par\pard\qj \li2265\ri1503\sb36\sl-553\slmult0\fi720 \up0 \expndtw0\charscalex104 \ul0\nosupersub\cf4\f5\fs24 Makrofag dapat berperan dalam melawan sel tumor dengan berperan \line \up0 \expndtw-3\charscalex100 sebagai \ul0\nosupersub\cf7\f8\fs24 Antigen Presenting Cell\ul0\nosupersub\cf4\f5\fs24 (APC) menghasilkan sitokin yang mengaktifkan \line \up0 \expndtw0\charscalex100 sel imunitas lain dan bertindak langsung sebagai efektor dengan melisiskan sel \line \up0 \expndtw-4\charscalex100 tumor apabila sudah diaktivasi oleh \ul0\nosupersub\cf7\f8\fs24 Macrofage Activating Factor \ul0\nosupersub\cf4\f5\fs24 (MAF).\ul0\super\cf5\f6\fs23 13,27 \par\pard\qj \li2265\ri1494\sb9\sl-551\slmult0\fi720 \up0 \expndtw0\charscalex101 \ul0\nosupersub\cf4\f5\fs24 Kemampuannya berikatan dengan sel tumor karena makrofag juga \line \up0 \expndtw0\charscalex102 mempunyai reseptor Fc yang mampu bekerjasama dengan IgG. Penyebab sel \line \up0 \expndtw0\charscalex100 tumor lisis akibat reaksi enzim lisosom, metabolit reaktif terhadap oksigen dan \line \up0 \expndtw0\charscalex100 NO. Makrofag juga aktif mensekresi TNF, IL-12 yang berperan memacu \line \up0 \expndtw0\charscalex107 proliferasi dan aktivasi Sel T CD4\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 , CTL serta sel NK. TNF sesuai dengan \line \up0 \expndtw-4\charscalex100 namanya mampu melisiskan sel tumor dengan berikatan pada reseptor permukaan \line \up0 \expndtw0\charscalex102 sel tumor dan menyebabkan nekrosis dari sel tumor dengan cara memobilisasi \line \up0 \expndtw-4\charscalex100 berbagai respon imun tubuh.\ul0\super\cf5\f6\fs23 8,13 \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb125\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 32 \par\pard\sect\sectd\fs24\paperw11900\paperh16840\pard\sb0\sl-240{\bkmkstart Pg11}{\bkmkend Pg11}\par\pard\qj \li2265\sb0\sl-550\slmult0 \par\pard\qj\li2265\sb0\sl-550\slmult0 \par\pard\qj\li2265\sb0\sl-550\slmult0 \par\pard\qj\li2265\ri1496\sb135\sl-550\slmult0\fi720 \up0 \expndtw-1\charscalex100 \ul0\nosupersub\cf4\f5\fs24 Diakhir peristiwa imunitas dihasilkan debris-debris sisa penghancuran sel, \up0 \expndtw0\charscalex100 selanjutnya peran makrofag yang membersihkan debris tersebut. Opsonisasi \up0 \expndtw0\charscalex100 komplemen dan antibodi terhadap debris-debris tersebut membantu proses fungsi \up0 \expndtw0\charscalex107 pembersihan makrofag. Akumulasi makrofag dalam tumor mungkin \up0 \expndtw0\charscalex106 menggambarkan interaksi makrofag kompleks dari beberapa faktor dan juga \up0 \expndtw0\charscalex103 kinetik produksi monosit oleh sumsum tulang. Jadi status fungsional makrofag \up0 \expndtw-3\charscalex100 dalam tumor juga berperan selain jumlahnya.\ul0\super\cf5\f6\fs23 19,27 \par\pard\ql \li2265\sb0\sl-276\slmult0 \par\pard\ql\li2265\sb201\sl-276\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf2\f3\fs24 2.3.2. Limfosit T sebagai efektor anti tumor \par\pard\qj \li2265\ri1499\sb36\sl-553\slmult0\fi719 \up0 \expndtw0\charscalex103 \ul0\nosupersub\cf4\f5\fs24 Subpopulasi limfosit T, limfosit T-\ul0\nosupersub\cf7\f8\fs24 helper\ul0\nosupersub\cf4\f5\fs24 dan T-\ul0\nosupersub\cf7\f8\fs24 sitotoksik\ul0\nosupersub\cf4\f5\fs24 sama-sama \line \up0 \expndtw0\charscalex104 berperan dalam mengeliminasi antigen tumor. Sel yang mengandung antigen \line \up0 \expndtw0\charscalex102 tumor akan mengekspresikan antigennya bersama molekul MHC kelas I yang \line \up0 \expndtw0\charscalex101 kemudian membentuk komplek melalui TCR \up0 \expndtw0\charscalex101 (\ul0\nosupersub\cf7\f8\fs24 T-cell Receptor\ul0\nosupersub\cf4\f5\fs24 ) dari sel T \par\pard\qj \li2265\ri1501\sb10\sl-550\slmult0\fi0 \up0 \expndtw-2\charscalex100 CD8\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 , selanjutnya mengaktifasi sel T-sitotoksik untuk menghancurkan sel tumor \up0 \expndtw0\charscalex105 tersebut. Sebagian kecil dari sel tumor juga mengekspresikan antigen tumor \up0 \expndtw-4\charscalex100 bersama molekul MHC kelas II, sehingga dapat dikenali dan membentuk komplek \up0 \expndtw0\charscalex102 dengan sel T CD4\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 dan mengaktifasi sel T-\ul0\nosupersub\cf7\f8\fs24 helper\ul0\nosupersub\cf4\f5\fs24 terutama \ul0\nosupersub\cf7\f8\fs24 subset \ul0\nosupersub\cf4\f5\fs24 Th1 untuk \up0 \expndtw0\charscalex100 mensekresi IFN dan TNF dimana keduanya akan merangsang sel tumor untuk \up0 \expndtw0\charscalex100 lebih banyak lagi mengekspresikan molekul MHC kelas I, sehingga akan lebih \up0 \expndtw-5\charscalex100 mengoptimalkan sitotoksisitas dari sel T CD8\ul0\super\cf5\f6\fs23 +\ul0\nosupersub\cf4\f5\fs24 .\ul0\super\cf5\f6\fs23 5,28 \ul0\nosupersub\cf4\f5\fs24 (Gambar 1) \par\pard\ql \li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb0\sl-230\slmult0 \par\pard\ql\li10003\sb45\sl-230\slmult0 \up0 \expndtw-3\charscalex100 \ul0\nosupersub\cf1\f2\fs20 33 \par\pard\sect\sectd\fs24\paperw11900\paperh16840{\shp{\*\shpinst\shpleft3892\shptop2267\shpright8634\shpbottom3054\shpbxpage\shpbypage\shpwr3\shpfblwtxt1\shpz109\shplid12{\sp{\sn shapeType}{\sv 75}}{\sp{\sn fBehindDocument}{\sv 1}}{\sp{\sn pib}{\sv 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