PERBEDAAN EKSPRESI INTERLEUKIN-6 OLEH MAKROFAG PADA JARINGAN KANKER KOLOREKTAL DAN JARINGAN NORMAL PADA PASIEN DENGAN KANKER KOLOREKTAL

Pebri Rahadian Ramlie, Prof. dr. Siti Nurdjanah, M.Kes, SpPD-KGEH

2013 | Tesis | S2 Ked.Klinik/MS-PPDS

Kanker kolorektal penyebab ke dua kematian akibat kanker di Amerika Serikat (AS), sekitar 50.000 pria dan wanita tiap tahunnya. Kanker ini terjadi pada 5% populasi dewasa di AS dan separuhnya menyebabkan kematian, di Indonesia belum terdapat data epidemiologinya, menurut data rekam medis di RSUP Dr. Sardjito Yogyakarta terdapat 119 (dari 28412 pasien) pasien pada tahun 2010 dan 124 (dari 28796 seluruh pasien) pada tahun 2011 dengan 3 dan 9 pasien meninggal selama perawatan (unpublished). Pathogenesis secara molekular pada kanker kurang dimengerti. Interleukin-6 (IL-6) adalah pleiotropic cytokine yang mempunyai fungsi fisiologis, menstimulasi aktivitas sel B memproduksi immunoglobulin dan berfungsi sebagai stimulasi hepatosit, sebagai sel B pertumbuhan yang disintesis oleh bermacam tipe sel, termasuk sel T, makrofag dan sel stromal sebagai respon menstimulasi Tumor Necrosing Factor α (TNF-α) dan interleukin-1 (IL-1). Aktifasi komplek IL-6 mengaktifkan Janus Kinase (JAK), Signal Transducer and Activators of Transcription (STAT) yang meregulasi proliferasi dan apoptosis. Tujuan penelitian ini untuk mengetahui apakah terdapat perbedaan ekspresi IL-6 oleh makrofag pada jaringan dengan kanker kolorektal dibandingkan dengan jaringan yang sehat pada pasien yang sama. Sampel penelitian jaringan histologi blok parafin di unit Patolodi Anatomi dari penderita kanker kolorektal yang telah menjalani operasi di RSUP Dr. Sardjito Yogyakarta bulan Januari 2010 hingga Desember 2011 yang memenuhi kriteria inklusi dan eksklusi sebanyak 25 jaringan pasien, sampel dipilih hingga jumlah terpenuhi. Sampel diwarnai dengan pewarnaan Imunno Histo Chemistry (IHC) didapatkan 14 sampel jaringan berjenis kelamin perempuan dan 11 sampel jaringan berjenis kelamin laki-laki, umur termuda 39 tahun dan umur tertua 84 tahun. Nilai rerata untuk ekspresi IL-6 pada jaringan normal 0.2616 dan untuk jaringan kanker 0.3924. Didapatkan perbedaan bermakna ekspresi IL-6 pada makrofag kedua jaringan dengan nilai p =0.001. Dalam penelitian ini ditemukan cut off point ekspresi IL-6 pada makrofag sebesar 0.35 dengan nilai sensitivitas = 72% ,spesitivitas = 72%, nilai duga positif = 72% dan nilai duga negatif = 72%.

INTERLEUKIN-6 EXPRESSION DIFFERENCES BY MACHROPHAGE IN COLORECTAL CANCER TISSUE AND NORMAL TISSUE IN PATIENTS WITH COLORECTAL CANCER Pebri Rahadian R, Siti Nurdjanah, Neneng Ratnasari Department of Internal Medicine-Scholl of Medicine Gadjah Mada University/Sardjito General Hospital Yogyakarta Colorectal cancer is the second cause of cancer deaths in the United States (U.S.), approximately 50,000 men and women every year. This cancer occurs in 5% of the adult population in the U.S. and half causing death, in Indonesia there has been no data on the epidemiology, according to medical records in Dr. Sardjito Yogyakarta there are 119 (out of 28412 patients) of patients in 2010 and 124 (from around 28 796 patients) in 2011 with respectively 3 and 9 patients died during treatment (unpublished). However, the molecular pathogenesis of these cancers is still poorly understood. Interleukin - 6 ( IL - 6 ) is a pleiotropic cytokine that has a physiological function , stimulates the activity of B cells produce immunoglobulin and serves as the hepatocyte stimulating factor , as a B cell growth are synthesized by various cell types , including T cells , macrophages and stromal cells in response to stimulate tumor necrosing factor α ( TNF - α ) and interleukin - 1 ( IL - 1 ) . Activation of the IL - 6 complex activates Janus Kinase ( JAK ) , signal transducer and activators of transcription ( STAT ) that regulate proliferation and apoptosis . The purpose of this study was to determine whether there are differences in the expression of IL - 6 by macgropage in colorectal cancer tissue compared with healthy tissue in the same patient . Histological tissue samples were paraffin blocks in unit Patolodi Anatomy of patients with colorectal cancer who had undergone surgery at Dr . Sardjito Yogyakarta between January 2010 and December 2011 who meet the inclusion and exclusion criteria as much as 25 patient tissue , samples were selected to sample size is met . Of samples stained with Histo Chemistry Imunno staining ( IHC ) was obtained tissue samples of 14 female and 11 tissue samples of male sex , age of the youngest 39 years old and the oldest was 84 years old . Mean value for IL - 6 expression in normal tissues is 0.2616 and 0.3924 for the cancerous tissue is . Obtained significant differences in the expression of IL - 6 both tissue macrophages with p = 0.001 . In this study also found a cut-off point IL - 6 expression in macrophages at 0.35 with a value of sensitivity =72 %, specivitivity = 72 %, positive predictiv value = 72% and negatif predictiv value = 72 %.

Kata Kunci : Kanker Kolorektal, IL-6, makrofag, IHC; Colorectal cancer, IL-6, macrophages, IHC