HUBUNGAN ANTARA EKSPRESI P53 MUTAN TERHADAP OPERABILITAS KANKER SERVIKS STADIUM IIB PASCA KEMOTERAPI NEOAJUVAN

NUR ROHMAH ARSYAD, dr. H. Risanto Siswosudarmo., Sp.OG(K).; dr. Ardhanu Kusumanto, Sp.OG(K)

2018 | Tesis-Spesialis | SP Ilmu Kebidanan dan Penyakit Kandungan

Latar Belakang: Tatalaksana kanker serviks stadium IIB sesuai rekomendasi FIGO adalah konkuren kemoradiasi. Tatalaksana kemoterapi neoajuvan yang dilanjutkan dengan histerektomi radikal merupakan tatalaksana alternaitf untuk memperbaiki harapan hidup secara keseluruhan. Patogenesis kanker serviks yang utama adalah infeksi virus Human Papilloma. Virus tersebut mempunyai protein E6 dan E7 yang akan menurunkan fungsi apoptosis p53. Menghilangnya fungsi p53 wild-type dan mutasi p53 berperan pada patogenesis kanker serviks. Tujuan: Mengetahui hubungan ekspresi p53 mutan dengan operabilitas kanker serviks stadium IIB pasca kemoterapi neoajuvan Material dan metode: Penelitian merupakan penelitian kohort prospektif dengan 40 dari 67 pasien yang memenuhi kriteria kelayakan. Blok parafin jaringan serviks dipersiapkan untuk dilakukan pengecatan immunohistokimia dengan antibodi antimutan p53 [Y5] ab32049, Abcam, USA. Kelompok penelitian terdiri atas kelompok ekspresi p53 mutan lemah dan kuat berdasarkan H score. Penilaian operabilitas dilakukan secara klinis. Variabel luar yang dievaluasi adalah usia, IMT, histopatologi, derajat diferensiasi, regimen, dan. Analisis data dengan uji Chi square dan uji regresi logistik Hasil: Angka operabilitas pasca kemoterapi sebesar 47,5%. Ekspresi lemah p53 mutan didapatkan pada 34 subyek (85%) dan ekspresi kuat pada 6 subyek (15%). Tidak ada hubungan yang signifikan antara ekspresi p53 mutan lemah vs. kuat terhadap operabilitas (p 0,45, RR 1,5, CI 95% 0,46-4,88). Hasil yang berbeda menunjukkan bahwa regimen kombinasi vs. tunggal mempengaruhi operabilitas (RR 1,87 vs. 1,35, CI 95% 1,01-3,44, p 0,06). Hasil analisis multivariat menunjukkan bahwa bahwa penggunaan regimen kombinasi secara signifikan mempengrauhi operabilitas (R 3,4, CI 95% 1,25-39,55, p 0,03). Kesimpulan: Ekspresi p53 mutan tidak berhubungan dengan operabilitas pasca kemoterapi neoajuvan, namun regimen kemoterapi kombinasi menunjukkan hasil sebaliknya

Background: The therapy for stage IIB cervical cancer according to FIGO is concurrent chemoradiation. The neoadjuvant chemotherapy followed by radical hysterectomy is an alternative therapy to improve the survival rate of cancer patients. Cervical cancer is mainly caused by the infection of Human Papilloma Virus (HPV), which contains protein E6 and E7 that downregulate the apoptotic function of p53. The absent of p53 wild-type and the present of p53 mutation play roles on the cervical cancer pathogenesis. Objective: To find out the association between the expression of mutant p53 to the stage IIB cervical cancer operability after neoadjuvant chemotherapy Material and method: This study was a prospective cohort, consisting of 40 out of 67 patients who met eligibility criteria. The parafin block from cervical tissue were processed for immunohistochemical staining of p53 using Anti-mutant p53 antibody [Y5] ab32049, Abcam, USA. Two study groups were assessed as: 1) weak and 2) strong expression of mutant p53 expression based on H-score. Both group (weak and strong) were comparable in age, BMI, histopathology, grade of differentiation, and regiment of.Evaluation of operability was performed clinically. Chi square test, and logistic regression were used for statistical analysis. Results: The rate of cervical cancer operability after chemotherapy was 19 out of 40 (47.5%). The weak expression of mutant p53was observed in 34 subjects (85%), and strong expression was 6 subjects (15%). There was no significant association between weak vs. strong expression of mutant p53 to the operability of the cancer (RR 1.5, CI 95% 0.46-4.88, p0.45). On the other hand, there was an association between combine vs. single regiment to operability (RR 1,87 vs. 1,35, CI 95% 1,01-3,44, p 0,06). Multivariate analysis showed that combine was significantly correlated to operability (RR 3.4, CI 95% 1.27-40.07, p 0.03). Conclusion: There was no association between expression of mutant p53 not to operability after neoadjuvant chemotherapy, but combine regiment was.

Kata Kunci : ekspresi p53 mutan, kanker serviks IIB, kemoterapi neoajuvan, operabilitas, expression of mutant p53, stage IIB of cervical cancer, neoadjuvant chemotherapy, operability