Hubungan antara Mutasi p53 dan Overall Survival pada Pasien Glioma CNS WHO grade 4

Fransisco Wahyu Santoso, dr. Ery Kus Dwianingsih, Ph.D., Sp.P.A., Subsp. MS (K), Subsp. SM (K); Prof. Dr. dr. Irianiwati, Sp.P.A., Subsp. OGP (K)

2025 | Tesis-Spesialis | S2 Ilmu Patologi Anatomi

Latar Belakang: Glioma CNS WHO grade 4 adalah tumor otak primer ganas tersering. Protein p53 sebagai “Guardian of the Genome” merupakan regulator utama berbagai proses seluler yang dapat mengakibatkan apoptosis dan penghentian siklus sel, serta mengontrol proliferasi sel, survival, dan integritas genomik. Mutasi p53 pada glioma dapat menurunkan kemosensitivitas terhadap temozolomide, meningkatkan instabilitas genomik & kerusakan DNA, serta meningkatkan resistensi terhadap terapi, yang dapat mempengaruhi survival. Tujuan dari penelitian ini adalah untuk mengetahui hubungan antara mutasi p53 dengan overall survival pada pasien glioma CNS WHO grade 4.

Metode: Penelitian ini menggunakan pendekatan studi retrospective cohort, dengan menggunakan sampel formalin-fixed paraffin-embedded pasien glioma CNS WHO grade 4 di RSUP Dr. Sardjito, tahun 2017 sampai dengan 2023. Status mutasi p53 ditentukan dari pemeriksaan imunohistokimia. Overall survival dianalisis dengan kurva Kaplan-Meier. Hubungan mutasi p53, jenis kelamin, usia, terapi, mutasi IDH1, dan metilasi MGMT terhadap overall survival masing-masing dianalisis dengan log-rank test. Hubungan usia dan jenis terapi terhadap overall survival, dianalisis multivariat dengan Cox-proportional hazard.

Hasil dan Pembahasan: Dari 94 sampel, didapatkan 70,2% p53 mutant dan 29,8% p53 wild-type. Analisis bivariat dengan log-rank test menunjukkan tidak didapatkan hubungan antara mutasi p53 dan overall survival pada pasien glioma CNS WHO grade 4. Analisis multivariat dengan Cox-proportional hazard menunjukkan bahwa pasien glioma CNS WHO grade 4 yang mendapatkan terapi kombinasi pembedahan, radioterapi, dan kemoterapi memiliki overall survival yang lebih baik (tiga kali lebih lama) dibandingkan dengan yang hanya mendapatkan terapi pembedahan saja (HR 2.96, 95% CI 1.718-5.099, p < 0 xss=removed>

Kesimpulan: Studi ini menunjukkan bahwa mutasi p53 bukan merupakan faktor prognostik independen terhadap overall survival pada pasien glioma CNS WHO grade 4, sedangkan jenis terapi dan usia dapat digunakan sebagai faktor prognostik independen terhadap overall survival pada pasien glioma CNS WHO grade 4.

Background: Glioma CNS WHO grade 4 is the most common malignant primary brain tumor. The p53 protein, known as the "Guardian of the Genome," is a crucial regulator of various cellular processes that can lead to apoptosis and cell cycle arrest, as well as controlling cell proliferation, survival, and genomic integrity. p53 mutations in glioma can reduce the chemosensitivity to temozolomide, increase genomic instability and DNA damage, and enhance resistance to therapy, affecting survival. This study aims to determine the association between p53 mutations and overall survival in glioma CNS WHO grade 4 patients.

Method: This study used a retrospective cohort approach using formalin-fixed paraffin-embedded glioma CNS WHO grade 4 patient samples at Dr. Sardjito General Hospital from 2017 to 2023. The p53 mutation status is determined through immunohistochemistry testing. Overall survival was analyzed using Kaplan-Meier curves. The association of p53 mutation, gender, age, treatment, IDH1 mutation, and MGMT methylation to overall survival was analyzed bivariate using the log-rank test. The association of age and type of treatment to overall survival was analyzed multivariate using Cox-proportional hazards.

Results and Discussion: Out of 94 samples, 70.2% were identified as p53 mutant, and 29.8% as p53 wild-type. The log-rank test bivariate analysis revealed no association between p53 mutations and overall survival in glioma CNS WHO grade 4 patients. Cox-proportional hazard multivariate analysis showed that glioma CNS WHO grade 4 patients receiving combined treatment of surgery, radiotherapy, and chemotherapy had better overall survival (three times longer) compared to those receiving only surgery (HR 2.96, 95% CI 1.718-5.099, p < 0 xss=removed>

Conclusion: This study shows that p53 mutation is not an independent prognostic factor for overall survival in glioma CNS WHO grade 4 patients, whereas the type of therapy and age can be used as independent prognostic factors for overall survival in glioma CNS WHO grade 4 patients.

Kata Kunci : glioma CNS WHO grade 4, p53, overall survival