Hubungan Ekspresi Imunohistokimia Anaplastic Lymphoma Kinase (ALK) dengan Grading Histopatologi Endometrioid Endometrial Carcinoma (EEC)

Abstract

Background: EEC is a primary epithelial malignant tumor in the endometrium, a glandular neoplasm with an acinar, papillary or partially solid configuration. Histopathological grading is made based on the degree of structural differentiation and cell atypia. The ALK gene is oncogenic in three ways; 1) forming a fusion gene with one of several other genes 2) obtaining additional copies of the gene 3) mutation of the actual DNA code for the gene itself. ALK rearrangement detection was carried out in 3 ways, namely Real-Time Polymerase Chain Reaction (RT-PCR), Fluorescence In Situ Hybridization (FISH), Immunohistochemistry (IHC). EEC molecular examination was found to contain inversion of chromosome 2 which resulted in the EML4-ALK gene fusion. Confirmation of immunohistochemical examination showed excess ALK in EEC even though only part of the tumor. Objective: To analyze the relationship between ALK immunohistochemical expression and EEC histopathological grading. Methods: Paraffin blocks from 31 EEC patients were slaid and then stained with ALK Immunohistochemistry was used to study ALK Immunohistochemical expression. The basic characteristics of the sample are obtained through Medical Records. The relationship between ALK expression and histopathological grading was analyzed using SPSS version 22 Conclusion: The identification of 31 samples of EEC sufferers was obtained that the mean age of EEC patients was 53.4 ± 14.1. with the majority in the 51-60 year age group (35.3%). The frequency distribution of EEC patients with grade I histopathology was mostly found, namely 14 people (45.2%). A positive ALK expression was found in 54.8% of cases while a negative one was 45.2%.

Latar Belakang: EEC adalah tumor ganas epitel primer di endometrium, neoplasma kelenjar dengan konfigurasi asinar, papiler atau sebagian padat. Grading histopatologi dibuat berdasarkan tingkat diferensiasi struktural dan atipia sel. Gen ALK bersifat onkogenik dengan tiga cara; 1) membentuk gen fusi dengan salah satu dari beberapa gen lainnya 2) mendapatkan salinan gen tambahan 3) mutasi kode DNA aktual untuk gen itu sendiri. Deteksi rearrangement ALK dilakukan dengan 3 cara yaitu Real-Time Polymerase Chain Reaction (RT-PCR), Fluorescence In Situ Hybridization (FISH), Immunohistochemistry (IHC). Pemeriksaan EEC secara molekuler ditemukan mengandung inversi kromosom 2 yang menghasilkan fusi gen EML4-ALK. Konfirmasi pemeriksaan imunohistokimia menunjukkan ALK berlebih pada EEC walaupun hanya sebagian tumor. Tujuan: Menganalisa hubungan ekspresi Imunohistokimia ALK dengan grading histopatologi EEC. Metode: Blok parafin dari 31 penderita EEC dibuat slaid kemudian diwarnai dengan Imunohistokimia ALK digunakan untuk meneliti ekspresi Imunohistokimia ALK. Karakteristik dasar sampel didapatkan melalui Rekam Medis. Hubungan ekpresi ALK dengan grading histopatologi dianalisis menggunakan SPSS versi 22. Hasil: Tidak terdapat hubungan signifikan antara ekspresi Imunohistokimia ALK dengan grading histopatologi EEC (p>0,05). Simpulan: Identifikasi 31 sampel penderita EEC didapakan rerata usia penderita EEC 53,4 ±14,1. dengan sebagian besar pada kelompok usia 51-60 tahun (35,3%). Distribusi frekuensi penderita EEC dengan histopatologi grade I paling banyak dijumpai yaitu 14 orang (45,2%). Ekspresi ALK positif dijumpai 54,8% kasus sementara yang negatif 45,2%.