ABSTRAK PERBEDAAN KADAR CANCER ANTIGEN 125 DAN HUMAN EPIDIDIMIS PROTEIN 4 PADA PASIEN KANKER OVARIUM EPITELIAL TIPE I DAN TIPE II Pande Made Angger Parameswara Bagian Obstetri & Ginekologi Fakultas Kedokteran Universitas Udayana/ RSUP Sanglah
Kanker ovarium merupakan penyebab kelima kematian akibat kanker pada wanita dan merupakan penyebab utama kematian dari keganasan ginekologi di Amerika. Kanker ovarium pada stadium awal tidak menunjukkan gejala klinis yang khas, sehingga diperlukan metode skrining yang lebih akurat. Beberapa biomarker marak dipelajari, dan CA125 dan HE4 adalah yang paling populer. Tujuan umum penelitian ini adalah untuk mengetahui peran kadar CA125 dan HE4 sebagai faktor risiko terjadinya ovarium tipe epithelial tipe I dan tipe II. Merupakan studi observasional crossectional terhadap 24 pasien kanker ovarium epithelial yang datang ke Poliklinik, ruang rawat inap ginekologi, serta IRD Obstetri dan Ginekologi RSUP Sanglah mulai bulan Januari 2015 sampai dengan bulan Desember 2015. Data kemudian diolah dengan piranti lunak SPSS. Tidak didapatkan perbedaan bermakna dari usia rata-rata dan paritas sampel (p > 0,05). Dengan uji t-independent ditunjukkan bahwa terdapat perbedaan kadar CA125 dan Human Epididimis Protein 4 pada kanker ovarium epitelial tipe I dan tipe II secara bermakna (p<0,05). Hasil penelitian kami adalah sejalan dengan berbagai penelitian lainnya yang mendukung penggunaan keduanya. Namun disarankan untuk melakukan penelitian lebih lanjut untuk menemukan tumor marker yang lebih akurat untuk memprediksi kanker ovarium. Kata Kunci: kanker ovarium, CA125, HE4, skrining
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ABSTRACT THE DIFERENCE OF CANCER ANTIGEN 125 AND HUMAN EPIDIDIMIS PROTEIN 4 IN BETWEEN TYPE I AND TYPE II OVARIAN CANCER Pande Made Angger Parameswara Department of Obstetrics and Gynaecology Faculty of Medicine The University of Udayana/ Sanglah Hospital Ovarian cancer is the 5 th leading cause of death in female and is the main cause of death in gynaecologic cancer in U.S. Early stage ovarian cancer does not show specific clinical sign, thus, an accurate screening method is essential. Some biomarkers are potential, CA125 & HE4 are the most extensively studied. The aim of this study is to determine the role of CA125 & HE4 serum concentration as the risk factor of type I and type II ovarian cancer. This is an observational crossectional study involving 24 epithelial ovarian cancer cases, who visited Obstetrics and Gynecology polyclinic, ward, or emergency room from January 2015 to December 2015. Data analyzed with SPSS. No difference was observed in mean age and parity of both groups (p > 0,05). With using t-independent test showing the difference of CA125 and Human Epididimis Protein 4 on ovarian cancer type I and type II significantly (p<0,05). These results support previous studies that suggest the use of both markers. But it is still reccomended to do further research to determine a more accurate screening method in predicting ovarian cancer. Keywords: ovarian cancer, CA125, HE4, screening
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DAFTAR ISI Halaman SAMPUL DALAM .................................................................................................. i PRASYARAT GELAR ........................................................................................... ii LEMBAR PERSETUJUAN................................................................................... iii PENETAPAN PANITIA PENGUJI ...................................................................... iv SURAT PERNYATAAN BEBAS PLAGIAT.........................................................v UCAPAN TERIMA KASIH .................................................................................. vi ABSTRAK ........................................................................................................... viii ABSTRACT .......................................................................................................... ix DAFTAR ISI ............................................................................................................x DAFTAR TABEL ................................................................................................ xiii DAFTAR GAMBAR ........................................................................................... xiv DAFTAR SINGKATAN DAN LAMBANG.........................................................xv DAFTAR LAMPIRAN ........................................................................................ xvi BAB I
PENDAHULUAN ....................................................................................1 1.1 Latar Belakang ....................................................................................1 1.2 Rumusan Masalah ............................................................................... 5 1.3Tujuan Penelitian .................................................................................6 1.4 Manfaat Penelitian ..............................................................................6 1.4.1 Manfaat bagi ilmu pengetahuan ..............................................6 1.4.2 Manfaat bagi pelayanan ..........................................................6
BAB II TINJAUAN PUSTAKA ...........................................................................7 2.1 Kanker Ovarium .................................................................................7 2.1.1 Epidemiologi Kanker Ovarium ..................................................7 2.1.2 Patogenesis Kanker Ovarium.....................................................8
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2.1.3 Histopatologi Kanker Ovarium .................................................8 2.1.4 Stadium Kanker Ovarium ........................................................14 2.1.5 Penatalaksanaan Kanker Ovarium ...........................................16 2.2 CA-125 ..............................................................................................17 2.2.1 Struktur CA-125 .......................................................................19 2.2.2 Fungsi CA-125 .........................................................................21 2.2.3 Ekspresi CA-125 pada kanker Ovarium tipe epithelial............22 2.2.4 Peran CA-125 Sebagai Tumor Marker pada kanker ovarium ..22 2.3 Human Epididimis Protein 4 .............................................................24 2.3.1 Struktur HE 4 ..........................................................................25 2.3.2 Fungsi HE 4 ............................................................................27 2.3.3 Ekspresi HE 4 pada Kanker Ovarium tipe epithelial ..............28 2.3.4 Peran HE4 Sebagai Tumor Marker pada Kanker Ovarium .....28 BAB III KERANGKA BERPIKIR DAN HIPOTESIS PENELITIAN ................32 3.1 Kerangka Berpikir .............................................................................32 3.2 Konsep Penelitian..............................................................................33 3.3 Hipotesis Penelitian...........................................................................34 BAB IV METODOLOGI PENELITIAN .............................................................35 4.1 Rancangan Penelitian ........................................................................35 4.2 Tempat dan Waktu Penelitian ...........................................................35 4.3 Populasi Penelitian ............................................................................36 4.4 Sampel Penelitian ..............................................................................36 4.4.1 Kriteria inklusi ........................................................................36 4.4.2 Kriteria eksklusi ......................................................................37 4.4.3 Perhitungan besar sampel ........................................................37 4.4.4 Cara pengambilan sampel .......................................................38 4.5 Variabel Penelitian ............................................................................38
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4.5.1 Identifikasi variabel .................................................................38 4.5.2 Definisi operasional variabel...................................................38 4.6 Alur Penelitian ..................................................................................39 4.7 Pengumpulan dan Analisis Data .......................................................40 4.7.1 Pengumpulan data ...................................................................40 4.7.2 Analisis data ............................................................................41 BAB V HASIL PENELITIAN. ........................................................................... 42 5.1 Distribusi Karakteristik Umur dan Paritas pada Pasien Kanker Ovarium Epithelial Tipe I dan Tipe II................................. 42 5.2 Perbedaan Kadar Ca125 pada Kanker Ovarium Epitelial Tipe I dan Tipe II ............................................................................................. 43 5.3 Perbedaan Kadar Human Epididimis Protein 4 pada Kanker Ovarium Epitelial Tipe I dan Tipe II………………………………………..43 BAB VI PEMBAHASAN. .................................................................................... 45 6.1 Karakteristik Subyek. ....................................................................... 45 6.2 Perbedaan Kadar Ca125 dan Human Epididimis Protein 4 pada Kanker Ovarium Epitelial Tipe I dan Tipe II……………………………45 BAB VII SIMPULAN DAN SARAN. ................................................................. 50 7.1 Simpulan. ......................................................................................... 50 7.2 Saran. .................................................................................................50 DAFTAR PUSTAKA ............................................................................................51 LAMPIRAN… .......................................................................................................57
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DAFTAR TABEL Halaman 2.1. Klasifikasi Histologi Kanker Ovarium Tipe Ephitelial WHO ........................12 2.2 Kriteria Stadium Kanker Ovarium Menurut FIGO .........................................14 5.1 Distribusi Karakteristik Umur dan Paritas pada Pasien Kanker Ovarium Epithelial Tipe I dan Tipe II. ........................................................................... 42 5.2 Hubungan antara Kadar CA125 dengan Kanker Ovarium Epithelial tipe II.43 5.3 Hubungan antara Kadar HE4 dengan Kanker Ovarium Epithelial tipe II ...... 44
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DAFTAR GAMBAR Halaman 2.1 Pembagian Tumor Ovarium Berdasarkan Sel Asalnya ....................................10 2.2 Struktur CA-125 ...............................................................................................20 2.3 HE4 diekspresikan pada epididimis pria ..........................................................26 3.1 Konsep Penelitian.............................................................................................33 4.1 Rancangan penelitian. ......................................................................................35 4.2 Alur Penelitian. ................................................................................................41
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DAFTAR SINGKATAN DAN LAMBANG
ACS
: American Cancer Society
FIGO
: International Federation of Gynecology and Obstetrics
CA 125
: Cancer Antigen 125
HE-4
: Human Epididimis Protein 4
YKI
: Yayasan Kanker Indonesia
HGSC
: High Grade Serous Carcinoma
TP 53
: Tumor supressor gen 53
DNA
: Deoxyribose Nucleic Acid
EGF
: Epidermal Growth Factor
SEA
: Sea urchin sperm protein, Enterokinase dan Agrin
WAP
: Whey Acidic Protein
WFDC
: Whey acidic Four – Disulfide Core
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DAFTAR LAMPIRAN Halaman Lampiran 1 Informed Consent ..............................................................................57 Lampiran 2 Pernyataan Persetujuan Mengikuti Penelitian ...................................58 Lampiran 3 Lembar Pengumpulan Data ................................................................59 Lampiran 4 Rencana Anggaran Biaya Penelitian ..................................................60 Lampiran 5 Analisa Data .......................................................................................61
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