Tesis

Perbandingan instabilitas mikrosatelit dan variasi ekspresi protein mismatch repair pada kanker kolorektal = Comparasion microsatellite instability and variation mismatch repair protein expression in colorectal cancer.

Pendahuluan : Berdasarkan data Riset Kesehatan Dasar (Riskesdas) 2013, prevalensi tumor/kanker di Indonesia adalah 1,4 per 1000 penduduk dengan insidensi kanker kolorektal (KKR) sebanyak 27.600. Salah satu penyebab terjadinya KKR adalah instabilitas mikrosatelit yang disebabkan oleh mutasi dari gen mismatch repair (MMR). Ekspresi protein MMR positif (proficient) menyebabkan mikrosatelit stabil (MSS). Ekspresi MMR yang tidak lengkap (partial) pada KKR kemungkinan dapat menyebabkan keadaan MSS atau Instabilitas mikrosatelit (MSI). Tujuan penelitian ini adalah melihat kesesuaian instabilitas mikrosatelit dengan variasi ekspresi protein MMR pada KKR. Metode: Telah dilakukan analisis fragmen berbasis PCR menggunakan probe BAT 25 dan BAT 26 pada 34 kasus KKR dengan status MMR yang telah diketahui berdasarkan hasil pemeriksaan Immunohistokimia (IHK) terhadap MutL homolog 1 (MLH1) dan muts protein homolog 2 (MSH2), hasil analisis MMR 12 positif (proficient), 12 Negatif (deficient) dan 10 positif parsial (partial loss). Hasil Penelitian: Berdasarkan nilai kappa, terdapat kesesuaian antara instabilitas mikrosatelit dengan ekspresi protein MMR dengan nilai 0,917 sensitifitas sebesar 92%, spesifisitas 99%. Hasil penelitian analisis fragmen pada 10 kasus MMR positif parsial dibandingkan dengan status MMR positif (proficient) pada sampel, terdapat kesesuaian dengan nilai kappa 0,542 sensitifitas 98% dan spesifisitas 75%. Kesimpulan: Pemeriksaan IHK MMR dengan analisis fragmen memiliki kesesuaian tinggi. Sehingga IHK MMR dapat dipakai untuk menentukan status mikrosatelit pada KKR. Pada MMR positif parsial perlu dilanjutkan dengan pemeriksaan analisis fragmen berbasis PCR.
Kata Kunci: Instabilitas mikrosatelit, mismatch repair (MMR), ekspresi Protein, kanker kolorektal (KKR).


Background: Based on data from the Health Research (Riskesdas) in 2013, the prevalence of tumor / cancer in Indonesia is 1.4 per 1000 population with incidence of colorectal cancer (CRC) as many as 27,600. One of the causes of microsatellite instability CRC is caused by mutations of the gene mismatch repair (MMR). MMR protein expression positive (proficient) cause microsatellite stable (MSS). Expression of MMR incomplete (partial loss) on the CRC could potentially cause a state of MSS or microsatellite instability (MSI). The purpose of this study was to compare the microsatellite instability with MMR protein expression variation in CRC. Methods: There have been analyzes fragments based on PCR using probe BAT 25 and BAT 26 in 34 cases of CRC with MMR status already known based on the results of immunohistochemistry (IHC) used MutL homolog 1 (MLH1) and muts protein homolog 2 (MSH2). Results: Based on the kappa value, there high concordance between microsatellite instability with MMR protein expression with value of 0.917 sensitivity 92% and specificity 99%. Results fragment analysis on 10 cases of partial loss MMR status compared with the positive (proficient) in the sample, there is a kappa value 0.542 conformity with sensitivity 98% and specificity of 75% Conclusion: Examination of IHC MMR by fragment analysis has high compatibility. IHC MMR can be used to determine the status of microsatellites in CRC. In partial loss status should be continued extended testing with fragment analysis based on PCR.
Keywords: Microsatellite instability, mismatch repair (MMR), Protein expression, colorectal cancer (CRC).