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"ABSTRAKLatar Belakang: Kanker serviks stadium lanjut lokal (IIB-IIIB) masih menjadi beban kesehatan di Indonesia saat ini. Radiasi menjadi modalitas utama terapi pada stadium ini. Programmed Death-Ligand 1 (PD-L1) merupakan sebuah ligand yang diekspresikan pada sel tumor yang terkait dengan proses immune escape. Sampai saat ini belum diketahui karakteristik kadar PD-L1 pada karsinoma sel skuamosa (KSS) serviks stadium lanjut lokal serta pengaruh radiasi terhadap ekspresinya. Penelitian ini bertujuan untuk melihat karakteristik PD-L1 intratumoral pada kanker serviks stadium lanjut lokal serta pengaruh radiasi eksterna terhadap ekspresinya. Metode: Dilakukan pemeriksaan kadar PD-L1 pada sampel biopsi serviks dengan 2 metode, yaitu Enzyme Linked Immuno Sorbent Assay (ELISA) dan immunohistokimia (IHK). Pengambilan sampel dilakukan dua kali, yaitu preradiasi dan pascaradiasi eksterna. Dilakukan analisis statistik untuk mengetahui perbedaan kadar antara sebelum dan sesudah radiasi. Selain itu dilakukan analisis untuk melihat kesesuaian antara kadar yang ditunjukkan pada metode ELISA dengan metode IHK. Hasil: Didapatkan 29 sampel KSS serviks stadium lanjut lokal yang memenuhi kriteria inklusi dan eksklusi. Dari pemeriksaan IHK, didapatkan bahwa PD-L1 diekspresikan hampir pada seluruh subjek (96,5%). Didapatkan nilai median PD-L1 ELISA preradiasi 409,19 pg/mg protein (59,80-3011,30), pascaradiasi 444,40 pg/mg protein (27,24-3217,85). Tidak didapatkan perbedaan bermakna antara kedua kelompok tersebut (p = 0,804). Pada analisis receiver operating characteristics (ROC) didapatkan nilai ELISA >400 pg/mg protein bersifat prediktif menyebabkan terjadinya penurunan kadar ELISA pascaradiasi. Terdapat kesesuaian antara kadar PD-L1 metode ELISA dengan metode IHK, dimana nilai ELISA > 499 pg/mg protein cenderung menunjukkan nilai grade 3 pada pemeriksaan IHK. Kesimpulan: PD-L1 diekspresikan positif pada KSS serviks uteri stadium lanjut lokal. Tidak terlalu jelas efek radiasi dalam menyebabkan naik-turunnya ekspresi PD-L1. Pemeriksaan ELISA mempunyai potensi untuk dipertimbangkan mewakili hasil pemeriksaan IHK, namun perlu bukti yang lebih kuat berupa penelitian dengan jumlah sampel yang lebih banyak.

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ABSTRACTBackground: Locally advanced cervical cancer (IIB-IIIB) remains a health burden in Indonesia. Radiation is the main modality of therapy at this stage. PD-L1 is a ligand that is expressed in tumor cells associated with the immune escape process. Until now there is no clear characteristics of PD-L1 levels in locally advanced-stage cervical SCC and the effect of radiation on its expression. This study is aimed to look for the intratumoral PD-L1 characteristics in locally advanced cervical cancer and the effect of external radiation on its expression. Method: PD-L1 levels were examined on cervical biopsy samples using two methods, i.e. ELISA and IHC. Biopsy was carried out twice, preradiation and post-external radiation. Statistical analysis was performed to determine differences in levels between before and after radiation. In addition, an analysis was conducted to see the conformity between the levels indicated in the ELISA method and the IHC method. Results: Twenty nine samples of local advanced cervical SCC were obtained that met the inclusion and exclusion criteria. From the IHC examination, it was found that PD-L1 was expressed in almost all subjects (96.5%). The median PD-L1 concentration of ELISA PD-L1 preradiation was 409.19 pg / mg protein (59.80-3011.30), post-radiation 444.40 pg / mg protein (27.24-3217.85). No significant difference was found between the two groups (p = 0.804). In the ROC analysis it was found that ELISA values > 400 pg / mg protein were predictive to cause a decrease in postradiation ELISA levels. There is a conformality between the levels of PD-L1 ELISA method with the IHC method, where the ELISA value > 499 pg/mg of protein tends to show grade 3 values ​​on the IHC examination. Conclusion: PD-L1 was expressed positively in locally advanced cervical SCC. The effects of radiation in causing the ups and downs of the expression of PD-L1 is not very clear. ELISA examination has the potential to be considered as a representative to the results of the IHC examination, but stronger evidence is needed in the form of study with a larger number of samples."

"Latar Belakang : Pasien kanker serviks di Indonesia terbanyak dalam stadium lanjut. Terapi standarnya adalah radiasi. Respons terapi radiasi tidak selalu komplet. MnSOD merupakan garda terdepan melawan radikal bebas yang dihasilkan radiasi. Aktifitas MnSOD dipikirkan dapat digunakan sebagai prediktor respons terapi radiasi. Diperkirakan semakin tinggi aktifitas MnSOD akan semakin buruk respons radiasinya. Tujuan : Menilai aktifitas MnSOD pada biopsi KSS serviks stadium IIIB sebagai prediktor keberhasilan terapi radiasi. Metode : Penelitian potong lintang komparatif ini dilakukan di Divisi Onkologi Ginekologi, Departemen Obstetri dan Ginekologi FKUI, RSCM Jakarta dan Departemen Biokimia dan Biologi Molekuler FKUI. Dilakukan penelusuran data base penelitian sebelumnya untuk mengindentifikasi sampel respons positif dan negatif, dilanjutkan pemeriksaan aktifitas MnSOD dengan sprektrofotometri metode McCord dan Fridovich menggunakan kit RanSOD . Data komparatif yang didapat kemudian di analisis. Hasil : Didapatkan 76 sampel yang memenuhi kriteria inklusi terdiri dari respons positif 47 61,8 negatif 29 38,2 . Dilakukan kategorisasi aktifitas MnSOD dengan titik potong pada nilai 13,126 U/mL. Dengan uji chi-square didapat hubungan bermakna secara statistik antara aktifitas MnSOD pada pasien kanker stadium IIIB dengan respons terapi radiasi. Nilai RR sebesar 1,849 1.075-3.178, IK 95 . Kesintasan dengan analisis bivariat memakai metode Kaplan-Meier: pasien dengan aktifitas MnSOD cutoff < 13,126 U/mL memiliki tingkat kesintasan 1 tahun yang lebih baik 63 dibandingkan dengan pasien kanker serviks IIIB dengan nilai aktifitas MnSOD ge; 14 . Risiko kematian dengan pengujian bivariat metode regresi cox: pasien dengan aktifitas MnSOD cutoff 13,126 U/mL memiliki risiko kematian 1,055 kali IK 95 : 1,003-1,110 dibanding pasien dengan aktifitas MnSOD dibawah nilai cutoff. Dari analisis multivariat terlihat aktifitas MnSOD semakin kuat sebagai prediktor respons terapi radiasi. Kesimpulan : Aktifitas MnSOD tinggi pada jaringan KSS serviks stadium IIIB menghasilkan respons negatif dari terapi radiasi.

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Background: Most of the cervical cancer patients in Indonesia came with advanced stage. Therefore, the choice of treatment is radiotherapy. Although, radiotherapy does not always result in complete response. MnSOD is considered to be one the antioxidant enzyme which has the ability to work against free radicals. Its activity is expected to be acted as response predictor to radiotherapy treatment. It is hypothesized that high MNSOD activity tend to predict poor response of radiotherapy on advanced cervical cancer patients.

Objective : To investigate MnSOD activity on cervical SCC stage IIIB as a predictor of radiotherapy response.

Methods : It is a comparative cross sectional study conducted in the Gynecology Oncology Division, Obstetrics and Gynecology Department, Dr. Cipto Mangunkusumo Hospital Faculty of Medicine, University of Indonesia. Samples were collected from the tissue bank and research database. They were identified and divided into having positive or negative response to radiotherapy. In vitro experiment was conducted to measure the activity of MnSOD. Manganese superoxide dismutase was isolated using McCord and Fridovich method using RanSOD and the activity was analyzed using spectrophotometry. Data was then analyzed using SPSS.20 for comparative study.

Results : Seventy six samples were included in the study 47 61.8 with positive response and 29 38.2 with negative response on radiotherapy. Samples were then divided into having MnSOD activity of 13.126 U mL or 13.126 U mL. Univariate analysis chi square showed that there was statistically significant correlation between MnSOD activity and radiotherapy response in patients with cervical SCC stage IIIB RR 1.849 95 CI 1.075 3.178 . Survival analysis on the first year showed that patients with MnSOD activity 13.126 U mL had better survival than patients with MnSOD activity 13.126 U mL 63 vs 14 , Kaplan Meier study . Hazard ratio for overall survival was 1.055 95 CI 1.003 ndash 1.110 for patients with MnSOD activity of 13.126 U mL. Multivariate analysis showed that MnSOD activity was a strong predictor of radiotherapy response in this study.

Conclusion : This in vitro study showed that high activity of MnSOD was associated with poor response of radiotherapy for patients with cervical squamous carcinoma stage IIIB. "