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Terapi target (targeted therapy) pada karsinoma kolorektal merupakan terapi alternatif yang diharapkan memberikan hasil yang lebih baik diantaranya dengan pemberian metabolit aktif vitamin D, yaitu calcitriol dan inhibitor Phosphatidyl Inositol 3 Kinase (PI3K). Penelitian ini bertujuan untuk mengetahui korelasi imunoekspresi VDR dan PI3K terhadap derajat diferensiasi adenokarsinoma kolorektal. Penelitian ini menggunakan desain potong lintang dengan analisis kategorik dari 30 blok parafin adenokarsinoma kolorektal (kelompok low grade dan high grade masing-masing 15 kasus) dari Departemen Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/RSUP Hasan Sadikin Bandung. Analisis Lambda menunjukkan bahwa imunoekspresi VDR dan PI3K masing-masing memengaruhi diferensiasi adenokarsinoma kolorektal (p=0,029, p=0,0225, R= 0,533). Berdasarkan nilai p, PI3K lebih kuat daripada VDR dalam memengaruhi derajat diferensiasi. Analisis Spearman menunjukkan imunoekspresi VDR dan PI3K tidak terbukti berkorelasi dengan diferensiasi (p=0,186, p>0,05, R: 0,248) secara bersamaan/simultan. Imunoekspresi VDR dan PI3K berkorelasi positif dengan kelompok low grade. Disimpulkan bahwa VDR tidak menggunakan jalur MAPK bersama-sama dengan PI3K dalam memengaruhi diferensiasi adenokarsinoma kolorektal. Kata kunci: Adenokarsinoma kolorektal, diferensiasi, imunoekspresi PI3K, imunoekspresi VDR Vitamin D Receptor (VDR) and Phosphatidylinositol 3-Kinase (PI3K) Independently Affected Colorectal Adenocarcinoma Differentiation Targeted therapy in carcinoma colorectal such as is as calcitriol and Phosphatidyl Inositol 3 Kinase (PI3K) is an alternative therapy for better treatment outcome. The aim of this study was to determine the correlation between VDR and PI3K immunoexpression with the degree of differentiation (grading) in colorectal adenocarcinoma. Cross-sectional, categorical analysis of 30 paraffin blocks of colorectal adenocarcinoma (low and high grade group, 15 cases each) obtained from Department of Pathology Faculty of Medicine, Universitas Padjadjaran/Dr Hasan Sadikin General Hospital Bandung. Analysis of Lambda showed that immunoexpression of VDR and PI3K affected differentiation of colorectal adenocarcinoma (p=0.029, p=0.0225, R=0.533). Based on p value, PI3k is stronger than VDR in influencing the degree of differentiation. Spearman analysis showed that simultaneous immunoexpression of VDR and PI3K was not shown to correlate with differentiation (p= 0186, p<0.05, R: 0.248). Positive immunoexpression of VDR and PI3K correlates with low-grade group. It can be concludes that VDR does not use the MAPK pathway together with PI3K to affect differentiation of colorectal adenocarcinoma. Keywords: Colorectal adenocarcinoma, differentiation, PI3K immunoexpression, VDR Immunoexpression