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Abstrak :
Latar belakang: Karsinoma sel hati (KSH) merupakan jenis keganasan primer hati tersering dengan gambaran histologik menunjukkan diferensiasi sel hepatoselular. Selain insiden yang tinggi, beban yang berat dari keganasan ini adalah prognosis yang sangat buruk dengan angka rekurensi yang tinggi. Terdapat banyak faktor resiko secara klinikopatologik yang telah diketahui mempengaruhi prognosis KSH, seperti kadar alfa fetoprotein, derajat diferensiasi, dan invasi mikrovaskular. Secara molekular, mutasi p53 dan β-catenin merupakan dua mutasi tersering dalam KSH. β-catenin merupakan protein multifungsi yang dikode oleh gen CTNNB1 yang dapat ditemukan pada 3 kompartemen sel, yaitu di membran sel, sitoplasma dan inti. Jalur Wnt/β-catenin meregulasi proses seluler yang terkait inisiasi, pertumbuhan, survival, migrasi, diferensiasi, dan apoptosis. Meski sudah banyak diketahui beberapa jalur patofisiologi molekular hepatokarsinogenesis, hubungan dengan aplikasi klinik membutuhkan pemahaman lebih mengenai hubungan sifat molekuler dan sifat fenotip tumor, terutama dalam penentuan faktor prognosis dan pengembangan terapi target. Penelitian ini bertujuan untuk menilai ekspresi β-catenin pada KSH dan hubungannya dengan berbagai faktor prognosis yaitu AFP, derajat diferensiasi dan invasi mikrovaskular. Bahan dan cara: Penelitian ini menggunakan desain potong lintang. Sampel terdiri atas 35 kasus KSH yang sudah ditegakkan diagnosisnya berdasarkan pemeriksaan histopatologik dan/atau imunohistokimia di RSCM dari Januari 2013 sampai September 2019. Dilakukan pulasan β-catenin dan analisis statistik dengan uji komparatif terhadap berbagai karakteristik klinikopatologik dan faktor resiko berupa AFP, derajat diferensiasi dan invasi mikrovaskular. Hasil: Terdapat perbedaan bermakna ekspresi β-catenin terhadap AFP (p=0,037) dan derajat diferensiasi (p=0,043) pada KSH. Ekspresi β-catenin pada inti dengan/tanpa sitoplasma lebih sering ditemukan pada kasus KSH dengan kadar AFP rendah dan derajat diferensiasi baik-sedang. Tidak ditemukan perbedaan bermakna ekspresi β-catenin terhadap invasi mikrovaskular pada KSH (p=1,000). Kesimpulan: Terdapat perbedaan bermakna ekspresi β-catenin terhadap AFP dan derajat diferensiasi pada KSH.

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Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, displaying histologically hepatocellular differentiation. In addition to its high incidence, the disease burden of HCC is due to its poor prognosis with high recurrence rate. Some of the previously known clinicopathologic prognostic factors of HCC include alpha-fetoprotein (AFP) level, tumor grade and microvascular invasion. At molecular level, p53 and β-catenin are the two most common driver mutations in HCC that are mutually exclusive. β-catenin is a multifunction protein that is encoded by CTNNB1 gen. It is found in 3 compartments of cells, which are membrane cell, cytoplasm and nucleus. Wnt/ β-catenin pathway regulates cellular process which is related to initiation, growth, survival, migration, differentiation and apoptosis. Although molecular pathogenesis pathways of hepatocarcinogenesis are known, clinical application warrants more understanding in terms of molecular characteristic and tumor phenotype, especially in determining prognosis and target therapy development. This current study aims to analyze the expression of β-catenin and its association with prognostic factors, such as AFP, tumor grade and microvascular invasion. Material and method: A cross-sectional study was conducted comprising 35 samples of surgically resected HCCs between January 2013 to September 2019 in Cipto Mangunkusumo General Hospital. The cases were diagnosed based on histopathological and immunohistochemical findings and was then performed β-catenin staining. β-catenin expression was analyzed with statistical tests to determine expression difference between AFP level, tumor grade and microvascular invasion. Result: There were statistically significant difference of β-catenin expression in AFP level and tumor grade (p=0.037 and 0.043, respectively). Nuclear with/without cytoplasmic expression of β-catenin was more frequently found in HCC with low AFP level and well-to-moderately differentiated tumors. No significant difference was observed in β-catenin expression between HCC with and without microvascular invasion (p=1.000). Conclusion: β-catenin expression was significantly different in AFP level and tumor grade.

Abstrak :
Latar Belakang: Karsinoma sel hati (KSH) adalah lesi neoplastik ganas pada hati tersering. Transformasi keganasan sel hati normal menjadi KSH melibatkan berbagai faktor seperti inflamasi dan perubahan genetik yang menyebabkan KSH menjadi sangat heterogen pada tingkat histologik dan molekular. Perbedaan fenotipe yang dipengaruhi berbagai perubahan molekular menghasilkan berbagai derajat diferensiasi, subtipe histologik dan gambaran klinik yang berbeda dan sebagian berhubungan dengan prognosis pada KSH. Mutasi pada gen TP53 yang berfungsi menontrol proliferasi sel melalui perbaikan DNA, apoptosis, dan penuaan sel terbukti sebagai salah satu perubahan molekular tersering pada KSH dan sering dikaitkan dengan beberapa faktor risiko, derajat diferensiasi, subtipe histologik tertentu dan prognosis. Penelitian ini bertujuan menginvestigasi ekspresi p53 pada derajat diferensiasi, subtipe histologik dan stadium patologi tumor KSH. Bahan dan cara: Penelitian dilakukan di Departemen Patologi Anatomik FKUI/RSCM, Jakarta terhadap 41 kasus KSH yang diperoleh seara reseksi. Sampel kasus diklasifikasikan berdasarkan kelompok derajat diferensiasi (WHO), subtipe histologik dan stadium patologi tumor. Selanjutnya dilakukan pulasan imunohistokimia (IHK) protein 53 (p53) pada seluruh kasus dan dilakukan analisis untuk mengetahui ekspresi p53 pada variabel penelitian. Hasil: Ekspresi p53 ditemukan pada 35 kasus (85%). Berdasarkan derajat diferensiasi, ekspresi p53 ditemukan paling banyak pada derajat diferensiasi sedang dan buruk, yaitu 21 dan 14 kasus (91% dan 93%). Ekspresi p53 berdasarkan stadium patologi tumor ditemukan paling banyak pada pT1b dan pT2, yaitu 8 dan 14 kasus ( 88% dan 93%). Berdasarkan subtipe histologik, seluruh kasus macrotrabecular massive (MTM) menunjukkan ekspresi p53 (4 kasus, 100%), subtipe clear cell (CC) terpulas pada 15 kasus (93%), klasik (CL) ditemukan 16 kasus (88%) dan tidak ditemukan ekspresi p53 pada seluruh kasus steatohepatitic (SH). Terdapat perbedaan rerata bermakna ekspresi p53 pada kelompok baik dan sedang (p=0,011), baik dan buruk (p=0,015) dan tidak terdapat perbedaan rerata bermakna antara kelompok sedang dan buruk (p=0,339). Tidak ditemukan perbedaan rerata bermakna ekspresi p53 pada seluruh kelompok stadium patologi tumor (p=0,948) dan subtipe histologik (p=0,076). Kesimpulan: Terdapat perbedaan bermakna ekspresi p53 pada KSH kelompok diferensiasi baik dan sedang serta baik dan buruk. ......Background: Hepatocellular cell carcinoma (HCC) is the most common malignant neoplastic lesion of the liver. Malignant transformation of hepatocytes involves various factors such as inflammation and genetic causing HCC to be very heterogeneous at the histological and molecular level. Differences in phenotypes affected by various molecular changes produce different differentiation grade, histological subtype, clinical features and prognosis. TP53 as one of the most common molecular changes in HCC play an important role in cycle cell by controlling cell proliferation through DNA repair, apoptosis and cellular senescence, associates with several risk factors such as certain differentiation grade, histologic subtypes, and prognosis. This current study aimed to investigate p53 expression at HCC’s differentiation grade, tumor pathology stage and histologic subtype. Materials and methods: The study was conducted at the Department of Anatomical Pathology FKUI / RSCM, Jakarta on 41 cases of resected HCC. Case samples are classified based on groups of differentiation grade (WHO), histologic subtypes and tumour pathology stage. Furthermore immunohistochemical (IHC) staining of protein 53 (p53) carry out in all cases and an analysis statistic was performed to evaluated the expression of p53. Results: p53 expression was found in 35 cases (85%). Based on the differentiation grade, the expression of p53 was found mostly in the moderate and poor differentiation (91%, 21 cases and 93%, 14 cases). Based on tumour pathology stage, p53 expression was found mostly in pT1b and pT2, which were 8 and 14 cases (88% and 93%). Based on histologic subtypes, all macrotrabecullar massive (MTM) cases showed p53 expression (4 cases, 100%), clear cell (CC) subtypes were in 15 cases (93%), classic (CL) 16 cases (88%) and negative expression was found in all cases of steatohepatitic (SH). There were significant differences in mean expression of p53 in the well and moderate groups (p = 0.011), well and poor (p = 0.015) and there were no significant mean differences between the moderate and poor groups (p = 0.339). There were no significant mean differences in p53 expression in all groups of tumour pathology stages (p = 0.948) and histologic subtypes (p = 0.076). Conclusion: There is significant difference mean of p53 expression in well and moderate as well as well and poor differentiation.