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"Latar Belakang: Kanker ovarium merupakan kanker kedelapan tersering, terhitung hampir 4% dari semua kanker pada perempuan di dunia. Kanker ovarium memiliki prognosis yang buruk dan angka kematian tertinggi. Setiap tahunnya terdapat 225.000 perempuan yang terdiagnosis kanker ovarium dan 140.000 perempuan meninggal disebabkan oleh penyakit ini. Berdasarkan jumlah tersebut, 90% kasus merupakan kanker ovarium epitelial. Bila berdasarkan stadium, lebih banyak pasien datang terdiagnosis dengan kanker ovarium stadium lanjut dibandingkan dengan stadium dini. Hal ini dikarenakan kanker ovarium bersifat asimtomatik, onset gejala yang terlambat dan belum adanya skrining yang terbukti efektif untuk kanker ovarium. Tujuan utama pengobatan kanker stadium lanjut adalah memperpanjang waktu untuk bertahan hidup dengan kualitas hidup yang baik dan tata laksana standarnya adalah operasi sitoreduksi. Di RSCM, evaluasi kesintasan dari pasien kanker ovarium epitelial stadium lanjut yang menjalani operasi sitoreduksi belum dianalisis.Tujuan: Mengetahui kesintasan pasien kanker ovarium stadium lanjut yang menjalani operasi sitoreduksi di RSCM dan juga mengetahui kesintasannya berdasarkan hasil histopatologi dan pemberian kemoterapi ajuvan.Metode: Penelitian ini merupakan penelitian kohort retrospektif dengan menggunakan data dari rekam medis. Pengambilan sampel dilakukan dengan cara consecutive sampling. Subjek penelitian adalah semua pasien kanker ovarium epitelial stadium lanjut yang menjalani operasi sitoreduksi pada bulan Januari 2013-Januari 2015 di RSCM.Hasil: Dari 48 subjek yang diteliti, didapatkan sebanyak 23 (48%) subjek menjalani operasi sitoreduksi optimal dan 25 (52%) subjek menjalani operasi sitoreduksi suboptimal. Didapatkan kesintasan 5 tahun pada pasien yang menjalani operasi sitoreduksi optimal sebesar 43,5%, sedangkan untuk sitoreduksi suboptimal sebesar 32%. Pada pasien yang menjalani operasi sitoreduksi optimal, yang diberikan kemoterapi ajuvan didapatkan kesintasan 5 tahun sebesar 40%, sedangkan pada pasien yang tidak diberikan sebesar 46,2%. Pada pasien yang menjalani operasi sitoreduksi suboptimal, yang diberikan kemoterapi ajuvan didapatkan kesintasan 5 tahun sebesar 40%, sedangkan pada pasien yang tidak diberikan sebesar 20%. Pada pasien dengan hasil histopatologi seromusinosum didapatkan kesintasan 5 tahun sebesar 100%, sedangkan untuk serosa, musinosa, endometrioid dan sel jernih berturut-turut sebesar 50%, 33,3%, 25%, dan 21,4%.Kesimpulan: Operasi sitoreduksi optimal memiliki kesintasan 5 tahun yang lebih baik dibandingkan dengan operasi sitoreduksi suboptimal. Operasi sitoreduksi suboptimal dan tidak dilanjutkan dengan pemberian kemoterapi ajuvan memiliki kesintasan yang buruk. Jenis histopatologi seromusinosum memiliki kesintasan yang lebih baik dibandingkan dengan jenis serosum, musinosum, endometrioid dan sel jernih.

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Background: Ovarian cancer is the eighth most common cancer, almost 4% of all cancers in women in the world. Ovarian cancer has a poor prognosis and the highest mortality rate. Every year 225,000 women are diagnosed with ovarian cancer and 140,000 women die from this disease. Based on this number, 90% of cases are epithelial ovarian cancer. Based on stadium, more patients diagnosed with advanced-stage ovarian cancer compared with early stage, because ovarian cancer is asymptomatic, delayed onset and there is no screening that has proven effective for ovarian cancer. The standard management for advanced stage ovarian cancer is debulking surgery. At RSCM, evaluation of survival of advanced stage epithelial ovarian cancer patients who were performed debulking surgery has not been analyzed.

Objective: Knowing the survival of patients with advanced-stage ovarian cancer who underwent debulking surgery at RSCM and also knowing their survival based on histopathological results and adjuvant chemotherapy.

Methods: This was a retrospective cohort study using data from medical records. Sampling was done by consecutive sampling. The subjects of this study were all patients with advanced-stage epithelial ovarian cancer patients who were performed debulking surgery in January 2013-January 2015 at RSCM.

Results: From the 48 subjects, 23 (48%) subjects were performed optimal debulking surgery and 25 (52%) subjects were performed suboptimal debulking surgery. Overall survival in patients undergoing optimal debulking surgery is 43.5% with a median survival rate of 39 months, while for suboptimal debulking surgery is 32% with a median survival rate of 29 months. In patients who underwent optimal cytoreduction surgery, those given adjuvant chemotherapy obtained a overall survival is 40%, whereas in patients who were not given is 46.2%. In patients who underwent suboptimal cytoreduction surgery, those who were given adjuvant chemotherapy found a overall survival rate of 40%, whereas in patients who were not given is 20%. In patients with histopathological results seromucinous obtained 5-year survival by 100%, while for serous, mucous, endometrioid and clear cells simultaneously were 50%, 33.3%, 25%, and 21.4%.

Conclusion: Optimal debulking surgery has a better 5-year survival compared to suboptimal debulking surgery. Suboptimal cytoreduction surgery and not followed by adjuvant chemotherapy has poor survival. The histopathological type of seromucinous has better survival compared with the types of serous, mucinous, endometrioid and clear cells."

"Latar Belakang : Sampai saat ini kanker ovarium masih menjadi salah satu kanker dengan angka mortalitas yang tinggi pada wanita dikarenakan tidak dijumpainya gejala yang khas sehingga lebih banyak kasus terdiagnosis pada stadium lanjut. Belum adanya metode skrining menjadikan pentingnya metode diagnostik yang mempunyai sensitivitas dan spesifisitas yang tinggi. Evaluasi biomarker yang baru diperlukan untuk dapat mendeteksi tumor ovarium ganas pada stadium awal.Objektif : Penelitian ini dilakukan untuk menilai ekspresi Immediate Early Response Gene X-1 (IEX-1) saliva sebagai prediktor keganasan pada tumor ovarium epitelial.Metode : Merupakan penelitian uji diagnostik pada pasien tumor ovarium yang direncanakan operasi elektif dengan mengambil 3-5 ml saliva pasien sebelum tindakan operasi. Subjek penelitian yang memenuhi kriteria inklusi dan eksklusi dibagi menjadi dua kelompok berdasarkan hasil histopatologi yaitu tumor ovarium epitelial jinak dan ganas. Dilakukan pemeriksaan ekspresi IEX-1 saliva dengan metode Real Time qPCR.Hasil : Hasil penelitian ini didapat dari 47 subjek, 22 subjek tumor ovarium epitelial ganas dan 25 subjek merupakan tumor ovarium epitelial jinak. Rerata ekspresi IEX-1 saliva lebih tinggi pada tumor ovarium epitelial jinak (1,976) dibandingkan ganas (0,554) (p<0,001). Didapatkan nilai AUC ekspresi IEX-1 0,949 (IK95% 0,894-1,000), nilai cut off point IEX-1 saliva ≥ 0.9115 dengan sensitivitas 84%, spesifisitas 86,4%, nilai duga positif 82,6% dan nilai duga negatif 87,5%. Terdapat hubungan yang signifikan antara ekspresi IEX-1 saliva dengan kejadian tumor ovarium epitelial ganas (OR 5,031, IK95% 2,039-12,41; p<0,001).Kesimpulan : Terdapat hubungan yang bermakna antara penurunan ekspresi IEX-1 saliva dengan kejadian tumor ovarium epitelial ganas dengan sensitivitas dan spesifisitas yang cukup baik.

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Backgound: Ovarian cancer is still one of the cancers with a high mortality rate in women because there are no typical symptoms so that more cases are diagnosed at an advanced stage. The absence of a screening method makes the importance of a diagnostic method that has high sensitivity and specificity. Evaluation of new biomarkers is needed to detect malignant ovarian tumors at an early stage.

Objectives: This study was conducted to assess the expression of salivary Immediate Early Response Gene X-1 (IEX-1) as a predictor of malignancy in epithelial ovarian tumors.

Methods: This is a diagnostic test study in ovarian tumor patients who are planned for elective surgery by taking 3-5 ml of patient's saliva before surgery. Research subjects who met the inclusion and exclusion criteria were divided into two groups based on the histopathological results, benign and malignant epithelial ovarian tumors. The salivary IEX-1 expression was examined using the Real Time qPCR method.

Results: The results of this study were obtained from 47 epithelial ovarian tumors subjects, 22 malignant tumors and 27 benign tumors. The mean salivary IEX-1 expression was higher in benign epithelial ovarian tumors (1.976) than in malignant (0.554) (p<0.001). The AUC expression value of IEX-1 was 0.949 (95% CI 0.894-1,000), salivary IEX-1 cut off point value was 0.9115 with sensitivity 84%, specificity 86.4%, positive predictive value 82.6% and negative predictive value 87, 5%. There was a significant relationship between salivary IEX-1 expression and the event of malignant epithelial ovarian tumors (OR 5.031, 95% CI 2.039-12.41; p<0.001).

Conclusions: There is a significant correlation between decreased salivary IEX-1 expression and the event of malignant epithelial ovarian tumors with a good sensitivity and specificity."

"[ABSTRAKPenelitian ini bertujuan untuk mengetahui gambaran umum kanker ovarium di Rumah Sakit Ciptomangunkusumo (RSCM) 5 tahun terakhir beserta faktor-faktor yang berhubungan dengan kanker ovarium. Penelitan ini mengambil data pasien kanker ovarium selain tipe borderline yang terdapat di Cancer Registry divisi Ginekologi Onkologi dan masih memiliki rekam medis di RSCM pada periode Januari 2010 – Desember 2014, dilakukan follow up untuk mengetahui kesintasan hidup selama 4 tahun. Kami mendapatkan 98 subyek penelitian. Pada penelitian ini didapatkan insidensi kanker ovarium terbanyak pada usia 45-54 tahun (33,6%), insidensi kanker ovarium menurun dengan bertambahnya jumlah anak, sebagian besar kanker ovarium merupakan tipe epitelial (76,5%) dan sebagian besar pasien didiagnosa pada stadium lanjut (55.1%). Kesintasan hidup 4 pasien kanker ovarium tipe epitelial 77%; tipe germinal 83.3%; tipe stroma 100%. Kesintasan hidup 4 tahun dengan terapi pembedahan 84.1%; pembedahan disertai kemoterapi adjuvan 83.3%; kemoterapi neoadjuvan sebelum pembedahan 68.4%. Terdapat 63% respon komplit pada kelompok kemoterapi adjuvan; dan 41.2% pada kelompok kemoterapi neoadjuvan.

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ABSTRACTThe aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.;The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.;The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy., The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.]"

"Ada beberapa metode untuk mendiagnosis karsinoma ovarium, diantaranya pemeriksaan ginekologi, pemeriksaan ultrasonografi, pemeriksaan tumor marker, dan gabungan beberapa pemeriksaan. Akan tetapi, gabungan pemeriksaan tersebut belum memberikan hasil spesifitas dan sensitivitas yang tinggi. Untuk itu masih diperlukan pemeriksaan lain untuk meningkatkan baik sensitivitas ataupun spesifitas, dan salah satu yang menarik untuk diteliti adalah pemeriksaan sitologi kavum uteri. Dengan pemeriksaan sitologi kavum uteri diharapkan dapat ditemukan sel-sel ganas yang berasal dari tumor ganas ovarium. Penemuan sel tumor ganas ovarium dimungkinkan karena adanya mekanisme peristaltik pada tuba fallopii dan tekanan negatif dari kavum uteri, sehingga memungkinkan terjadinya transportasi sel ganas ovarium ke dalam kavum uteri melalui tuba. Penelitian ini bertujuan mengetahui sensitivitas dan spesifitas pemeriksaan sitologi kavum uteri dalam mendeteksi keganasan ovarium dibandingkan dengan pemeriksaan histologi yang umum dilakukan. Penelitian ini merupakan uji diagnostik, dengan pemeriksaan histologi sebagai baku emas, untuk mengetahui sensitivitas, spesifisitas, nilai praduga positif, dan nilai praduga negatif pemeriksaan sitologi kavum uteri. Sebanyak 30 kasus masuk dalam penelitian ini. Ada beberapa faktor yang meningkatkan nilai positif sitologi kavum uteri, antara lain stadium, dan asites. Semakin tinggi stadium semakin besar nilai positif, adanya asites memperbesar kemungkinan positif. Pada uji diagnostik didapatkan sensitivitas sitologi kavum uteri sebesar 48%, spesifisitas 60%, nilai praduga positif 85,7%, dan nilai praduga negatif 18,8%. Kesimpulan: pemeriksaan sitologi kavum uteri dapat digunakan sebagai salah satu metode untuk membantu dalam mendiagnosis karsinoma ovarium. (Med J Indones 2004; 14: 92-6)

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There are several methods for diagnosing ovarian carcinoma, such as gynecological examination, ultrasonographic examination, and tumor marker examination. However, all these combinations have not yielded high specificity and sensitivity results. For this reason, it is necessary to perform other examinations to enhance both specificity and sensitivity, and one of them which is of interest to be studied is cytological examination of uterine cavity. By cytological examination of uterine cavity, it is hoped that malignant cells originating from ovarian malignant tumor can be found. Discovery of ovarian malignant cells is possible because of peristaltic mechanism in the fallopian tube and negative pressure from uterine cavity, that makes possible the transportation of ovarian malignant cells into uterine cavity through the tube. The objective of this study is to understand the sensitivity and specificity of cytological examination of uterine cavity in detecting ovarian malignancy. This study was a diagnostic test with histological examination as the gold standard, to understand sensitivity, specificity, positive prediction value, and negative prediction value of cytological examination of uterine cavity. A total of 30 cases were included in the study. A number of factors enhanced positive results in cytology of uterine cavity. Those factors were stage and ascites. The more advanced the stage, the greater the positive results, and the presence of ascites increased positive results. On diagnostic test, sensitivity of uterine cavity cytology was 48%, specificity 60, positive predictive value 85.7%, and negative predictive value 18.8% respectively. In conclusion, cytological examination of uterine cavity could be used as one of the methods in assisting the diagnosis of ovarian carcinoma. (Med J Indones 2004; 14: 92-6)"

"ABSTRAKNama :Nugraha Utama PelupessyProgram Studi :S3 Ilmu KedokteranJudul :Marker Cancer Stem Cells CD133, CD44, dan ALDH1A1 Sebagai Faktor Prognostik pada Kanker Ovarium Tipe Epitelial Kanker ovarium merupakan penyakit yang bersifat heterogen dan kebanyakan pasien datang dengan stadium lanjut. Kanker ovarium epitelial tipe II mempunyai sifat pertumbuhan tumor yang cepat dan secara genetik labil dibandingkan tipe I. Keberadaan cancer stem cells CSC dianggap sebagai salah satu faktor prognostik terjadinya kemoresisten dan kesintasan hidup yang rendah.Penelitian ini bertujuan untuk membuktikan CSC sebagai faktor prognostik dengan menggunakan marker CD133, CD44, dan ALDH1A1 pada kanker ovarium tipe epitelial.Marker CD133, CD44, dan ALDH1A1 diperiksa dengan imunohistokimia dan flowcytometry. Hasil ekspresi marker CSC pasien kanker ovarium tipe I dan tipe II dimasukkan kedalam suatu tabel yang dihubungkan dengan respons kemoterapi dan kesintasan hidup. Analisis data dilakukan dengan program computer STATA 14. Analisis kesintasan dilakukan dengan analisis Kaplan-Meier dan uji asumsi cox proportional hazard. Analisis multivariat dipakai untuk model prognosis selama 10 bulan. Sistem skoring dibuat dengan menggunakan receiver operating characteristic ROC curve analyses.Data demografi kelompok terbanyak adalah usia ge; 45 tahun; 40 sampel 72,7 , stadium I, 23 sampel 41,8 , diferensiasi buruk 30 sampel 54,5 , dan tipe II 16 sampel 29,1 . Perbedaan yang bermakna antara tipe histopatologi dengan marker CSC hanya terlihat pada marker CD44. Skor Prediksi Kemoresisten SPKr 10 bulan yang dihubungkan dengan 4 variabel yaitu usia ge; 45 tahun, tipe II, stadium III minus;IV, dan CD44 tinggi dengan ROC 72,47 dan probabilitas post test 82,5 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 negatif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841. Skor Prediksi Kematian SPKm 10 bulan yang dihubungkan dengan 3 variabel yaitu stadium III minus;IV, tipe II, dan CD44 tinggi dengan AUC 80,44 dan probabilitas post test 78,7 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 positif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841.Simpulan: Marker CD44 terbukti berperan pada kanker ovarium tipe II. Skor Prediksi Kemoresisten dan Skor Prediksi Kematian dapat ditentukan selain dengan faktor klinikopatologi, juga dengan memakai marker CSC. Kata kunci: ALDH1A1, CD44, CD133, CSC, kanker ovarium epitelial, kesintasan hidup, respons kemoterapi.

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ABSTRACTName : Nugraha Utama PelupessyStudy Program : Doctoral Program Medical SciencesTitle :Cancer Stem Cell CD133, CD44 andALDH1A1 Markers As Prognostic Factors on Epithelial Ovarian Cancer. Ovarian cancer is a heterogeneous disease and most of the patients came with an advanced stage. Epithelial ovarian cancer type II has the characteristic of rapid tumor growth and genetically more labile than that of type I. The presence of cancer stem cells CSC is considered as one of the prognostic factors of low mortality and survival.The aims of this study was to prove CSC as prognostic factors using CD133, CD44, and ALDH1A1 markers on epithelial ovarian cancer.Clinicopathology and demographic data were collected from medical records. CD133, CD44, and ALDH1A1 markers were examined with flowcytometry and immunohistochemistry. CSC marker expression of the patients with ovarian cancer type I and II was connected with chemotherapy and survival response. Data analysis was done by using STATA 14 software. Survival analysis was done by using Kaplan-Meier analysis and Cox proportional hazard test. Multivariate analysis is used for prognosis model for ten months. Receiver Operating Characteristic ROC curve analyses was used as the system scoring. The highest group demographic data were age ge; 45 years; 40 samples 72.7 , stage I, 23 samples 41.8 , poor differentiation 30 samples 54.5 , and type II 16 samples 29.1 . A significant difference between the histopathologic type and the CSC marker was seen only in CD44 marker. Chemoresistance Prediction Score in 10 months was associated with 4 variables ie age ge; 45 years, type II, stage III minus;IV, and CD44 high with ROC 72.47 and posttest probability 82.5 . The highest chemoresitency scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1, was 0.841. Mortality Prediction Score in 10 months was associated with 3 variables is stage III minus;IV, type II, and CD44 high with AUC 80.44 and posttest probability 78.7 . The highest mortality scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, positive CD133, high CD44, and high ALDH1A1, was 0.841. Conclusion: The CD44 marker has a role in type II ovarian epithelial cancer. Chemoresistance Prediction Score and Mortality Prediction Score can be determined from clinicopathological factors and using CSC marker. Keywords: ALDH1A1, CD44, CD133, chemotherapy response, CSC, Epithelial Ovarian Cancer, survival"

"Latar belakang: Kanker ovarium merupakan jenis kanker ke-3 yang paling sering dialami oleh wanita di Indonesia. Diagnosis yang terlambat berperan besar dalam tingginya angka mortalitas. Metode skrining cepat kanker ovarium semakin penting untuk diteliti, dengan beragam biomarker penanda kanker seperti CA-125, HE4, dan FOLR1 yang menawarkan indeks diagnostik dan kemudahan prosedur yang menjanjikan.Metode: Studi deskriptif desain potong lintang ini dilakukan di Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo, Jakarta pada Januari 2022 hingga Januari 2023. Kadar serum CA-125, HE4, dan FOLR1 dianalisis dari 48 subjek yang terbagi dalam kelompok tumor ovarium ganas dan jinak. Diagnosis pasti tumor merujuk hasil pemeriksaan histopatologis dan pencitraan. Data demografis pasien seperti usia, status menopause, ukuran tumor, hingga hasil analisis sitologi cairan asites dikumpulkan.Hasil: Hasil analisis demografis menunjukkan kecenderungan subjek menopause untuk memiliki tumor ovarium non-maligna (57,6% vs. 26,7%; p < 0,05), dan subjek dengan cairan asites ganas cenderung memiliki tumor ovaium maligna (3,0% vs. 40,0%; p < 0,05). Kadar ketiga biomarker serum meningkat pada kelompok tumor maligna, namun hanya HE4 (median 12,43 vs. 42,03; p < 0,05) yang memiliki perbedaan bermakna (CA-125 median 102,50 vs. 461,85; p = 0,062; FOLR1 median 0,070 vs. 0,172; p=0,213). Area under the curve (AUC) pada hasil analisis kurva receiver operating characteristic (ROC) menunjukkan hasil 0,630, 0,747, dan 0,794 secara berturut-turut untuk biomarker FOLR1, Ca125, dan HE4, dengan analisis beda proporsi signifikan pada titik potong 0,1165 ng/mL (Se 66,7%, Sp 60,6%), 208,00 U/mL (Se 73,3%, Sp 84,8%), dan 19,66 pg/mL (Se 86,7%, Sp 60,6%). Analisis kombinasi biomarker menunjukkan peningkatan sensitifitas namun penurunan spesifisitas.Kesimpulan: Kadar serum ketiga biomarker memiliki kemampuan yang baik sebagai prediktor keganasan tumor ovarium maligna. Pada populasi penelitian, HE4 secara tunggal memiliki indeks diagnostik terbaik, dan kombinasi biomarker tidak memberikan peningkatan kemampuan diagnostik.

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Background : Ovarian cancer is the third most common cancer in women in Indonesia. Late diagnosis significantly contributes to high mortality rates. Rapid screening methods for ovarian cancer are increasingly important, with biomarkers such as CA-125, HE4, and FOLR1 offering promising diagnostic indices and procedural ease.

Methods: This cross-sectional descriptive study was conducted at Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta from January 2022 to January 2023. Serum levels of CA-125, HE4, and FOLR1 were analyzed in 48 subjects divided into malignant and benign ovarian tumor groups. Tumor type diagnosis was based on histopathological examination and imaging. Patient demographic data including age, menopausal status, tumor size, and cytology analysis of ascitic fluid were collected.

Results: Demographic analysis showed tendencies of menopausal subjects to have non-malignant ovarian tumors (57.6% vs. 26.7%; p < 0.05), and subjects with malignant ascitic fluid were more likely to have malignant ovarian tumors (3.0% vs. 40.0%; p < 0.05). Serum levels of all three biomarkers were higher in the malignant group, but only HE4 (median 12.43 vs. 42.03; p < 0.05) showed significant differences (CA-125 median 102.50 vs. 461.85; p = 0.062; FOLR1 median 0.070 vs. 0.172; p = 0.213). The area under the curve (AUC) for the receiver operating characteristic (ROC) curve analysis showed 0.630, 0.747, and 0.794 for FOLR1, CA-125, and HE4, respectively. Significant cut-off points were 0.1165 ng/mL (Se 66.7%, Sp 60.6%), 208.00 U/mL (Se 73.3%, Sp 84.8%), and 19.66 pg/mL (Se 86.7%, Sp 60.6%). Biomarker combination analysis increased sensitivity but decreased specificity.

Conclusion: Serum levels of the three biomarkers are good predictors of malignancy in ovarian tumors. In this study population, HE4 alone had the best diagnostic index, and combining biomarkers did not enhance diagnostic capability."

"Kanker ovarium memiliki mortalitas mencapai 70%, dan 85% dari pasien yang datang pada kondisi stadium lanjut. Sebanyak > 80% pasien stadium lanjut merespons pada kemoterapi lini pertama yang menggunakan obat berbasis platinum, namun median kesintasan bebas penyakitnya (disease-free survival) hanya mencapai 18 bulan, sebagian besar merupakan pasien kambuh, dan tidak merespons pada kemoterapi lini berikutnya. Pada moda moda kemoresistensi, yang paling dapat diintervensi adalah adanya sel punca kanker (CSC) pada jaringan kanker ovarium pasien. Kemoresistensi pada CSC memiliki beberapa mekanisme berbeda, salah satunya adalah tingginya aktivitas protein ATM dan ATR yang dapat bersifat kompetitif terhadap obat berbasis platinum dalam berikatan dengan DNA. Selama ini, telah banyak penelitian eksperimental yang menarget CSC kanker ovarium, namun penelitian terbaru menggunakan RNA microarray menemukan bahwa gen ADAM19 diekspresikan secara eksklusif pada CSC kanker ovarium sehingga dapat digunakan sebagai marker spesifik. Oleh karena itu, penelitian ini ditujukan untuk mengeksplorasi kemoresistensi pada CSC kanker ovarium dari jaringan segar pasien dan korelasinya dengan ekspresi gen ATM dan ATR, serta mengonfirmasi ekspresi gen ADAM19 sebagai marker spesifik subpopulasi CSC kanker ovarium yang dipilah menggunakan metode MACS dengan penanda CD133. Dari 67 pasien subjek penelitian yang diambil dan dikultur jaringan metastasisnya, dua di antaranya dapat dikultur tanpa batas, menghasilkan kultur dengan dominan sel epitel, dan tidak mengalami senescence. Setelah itu, sel-sel kultur dipilah menggunakan MACS dengan penanda CD133 untuk mendapatkan CSC, kemudian diuji menggunakan metode pembuatan sferoid, RT-qPCR, dan uji kemoresistensi. Dari pembentukan sferoid yang dilakukan pada tiga jenis sel yang digunakan, yakni lini sel SKOV3, serta kultur primer OV1 dan OVM1, ditemukan secara konsisten bahwa jumlah sferoid yang didapatkan pada kultur CSC CD133+ lebih banyak dibandingkan main population (MP) dan CD133-. Dari RT-qPCR juga ditemukan secara konsisten bahwa seluruh ekspresi gen ATM, ATR, NANOG, ADAM19, Ki-67, dan kaspase-3 pada CSC CD133+ lebih tinggi dibandingkan MP dan CD133. Pada uji kemoresistensi terhadap kemoterapi karboplatin, didapatkan bahwa sel CD133+ juga lebih kemoresisten dibandingkan dengan MP dan CD133-. Berdasarkan uji korelasi Spearman Rho, ekspresi gen ATM dan ATR berkorelasi positif sedang menuju sangat kuat dengan sifat kemoresistensi terhadap karboplatin. Pada akhir penelitian, disimpulkan bahwa CSC dengan CD133+ memiliki kemampuan proliferasi yang lebih tinggi dengan ekspresi gen Ki-67 yang meningkat, memiliki stemness yang lebih kuat terlihat pada ekspresi gen Nanog-nya yang lebih tinggi, dan memiliki kemampuan kemoresistensi yang lebih besar ditunjukkan oleh ekspresi gen ATM dan ATR-nya yang tinggi serta berkorelasi positif dengan hasil uji kemoresistensi.

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Ovarian cancer has a mortality rate of up to 70% where 85% of patients present at an advanced stage. More than 80% of advanced stage patients respond to first-line chemotherapy using platinum-based drugs, but the median disease-free survival is only 18 months. Most patients relapse, and do not respond to subsequent lines of chemotherapy. In the chemoresistance modes, the easiest way to intervene is through the presence of cancer stem cells (CSC) in the patient's ovarian cancer tissue. Chemoresistance in CSC has several different mechanisms, one of which is the high activity of ATM and ATR proteins that can be competitive against platinum-based drugs in binding to DNA. So far, there have been many experimental studies targeting ovarian cancer CSCs, but a recent study using RNA microarray found that ADAM19 gene expression is expressed exclusively in ovarian cancer CSCs so that it can be used as a specific marker. Therefore, this study aimed to explore chemoresistance in ovarian cancer CSC from fresh patient’s tissue and its correlation with ATM and ATR gene expression, as well as to confirm ADAM19 gene expression as a specific marker for ovarian cancer CSC subpopulations sorted using the MACS method with the CD133 marker. Out of 67 patients who were the subjects of the study, the samples were taken and cultured for their metastatic tissues, 2 of them could be cultured indefinitely, could produce cultures with a predominance of epithelial cells, and did not experience senescence. After that, the culture cells were sorted using MACS with the CD133 marker to obtain CSC, then tested using the spheroid preparation method, RT-qPCR, and chemoresistance test. From the spheroid culture performed on the 3 types of cells used, namely the SKOV3 cell line, as well as OV1 and OVM1 primary cultures, it was found consistently that the number of spheroids obtained in CD133+ CSC cultures was higher than the main population (MP) and CD133-. From RT-qPCR it was also found consistently that all genes expression ATM, ATR, NANOG, ADAM19, Ki-67, and Caspase-3 in CD133+ CSCs were higher than MP and CD133. In the chemoresistance test to carboplatin chemotherapy, it was found that CD133+ cells were also more chemoresistant than MP and CD133-. Based on the Spearman Rho correlation test, ATM and ATR gene expression had a moderately strong positive correlation with chemoresistance to carboplatin. At the end of the study, it was concluded that CSCs with CD133+ had a higher ability to proliferate with increased expression of the Ki-67 gene, had stronger stemness as seen in the higher expression of the NANOG gene, and had greater chemoresistance ability as indicated by the expression of the ATM gene. and high ATR and positively correlated with chemoresistance test results."

"Penelitian ini bertujuan untuk membandingkan ROMA dengan RMI dalam memprediksi keganasan tumor ovarium epitelial di RS dr. Cipto Mangunkusumo (RSUPNCM). Penelitian ini merupakan uji diagnostik dengan desain potong lintang yang dilakukan di Departemen Obstetri dan Ginekologi, RSUPNCM. Pada penelitian ini, dari 213 subjek diperoleh sensitivitas dan spesifisitas RMI 85.3%, dan 66.3%, Nilai Duga Positif dan Negatif RMI 79.7%, dan 74.3%, Rasio Kemungkinan Positif dan Negatif RMI 2.53, dan 0.22; dan sensitivas dan spesifisitas ROMA 95.4%, dan 32.5%, Nilai Duga Positif dan Negatif 68.9%, dan 81.8%, Rasio Kemungkinan Positif dan Negatif 1.41, dan 0.14. AUC ROMA lebih baik daripada RMI, tetapi tidak bermakna secara statistik (seluruh kelompok: AUC 69.56%>67.49%, perbedaan AUC 0.0207, p 0.526; kelompok pascamenopause: AUC 91.47%>88.97%, perbedaan AUC 0.0250, p 0.0571; kelompok premenopause: AUC 86.20%>78.16%, perbedaan AUC 0.0804, p 0.0571). Pada titik potong ideal (RMI 330, ROMA premenopause 30,4; dan pascamenopause 53.1), ROMA mempunyai sensitivitas dan spesifitas yang lebih baik dibandingkan RMI (sensitivitas 82.31% vs 74.62%; spesifisitas 78.31% vs 75.9%). Dapat disimpulkan bahwa tidak terdapat perbedaan antara ROMA dengan RMI, tetapi sensitivitas dan spesifisitas ROMA lebih baik daripada RMI pada titik potong ideal.

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The purpose of this research is to compare ROMA with RMI to predict malignancy of ovarian tumor, epithelial type in Indonesia, especially at the Cipto Mangunkusumo hospital. It was a cross sectional study with a diagnostic design, which was performed in the Oncology Gyneology division. From 213 sampels, the RMI showed a sensitivity of 85.3%, a specificity of 66.3%, a PPV of 79.7%, a NPV of 74.3%, a LR+ of 2.53, LR- 0.22 and an accuracy of 0.77; while ROMA has a sensitivity of 95.4%, a specificity of 32.5%,a PPV 68.9% of, a NPV of 81.8%, a LR+ 1.41, LR- 0.14 and an accuracy of 0.71. Overall AUC ROMA indicated better results compared to those results using the RMI diagnostic method, (all groups: AUC 69.56%>67.49%, p 0.526; as with the postmenopause group: the AUC was 91.47%>88.97%, p 0.0571; and the premenopause group: the AUC 86.20%>78.16%, p 0.0571). At ideal the cut-off point (RMI 330, ROMA premenopause 30,4; and postmenopause 53.1), ROMA has shown better sensitivity and specificity than RMI (sensitivity 82.31% vs 74.62%; specificity 78.31% vs 75.9%). It can be concluded that there is no significantly different between ROMA and RMI, but at ideal cut off, sensitivity and specificity ROMA better than RMI."

"Kanker ovarium masih menempati urutan kedua terbanyak dalam keganasan ginekologi dan merupakan penyebab utama kematian akibat kanker pada perempuan. Banyak bukti menunjukkan bahwa kanker ovarium umunya dalam pengaruh stress oksidatif. Dalam penelitian ini bertujuan untuk mengetahui aktivitas stress oksidatif melalui pengukuran enzim Superoxide Dismutase (SOD) dan kadar Malondialdehyde (MDA) pada penderita keganasan ovarium dibandingkan dengan penderita tumor jinak ovarium. Penelitian dilakukan dengan uji potong-lintang yang dilaksanalan di Ruang Rawat Kebidanan Ginekologi RSCM Jakarta, RS Persahabatan Jakarta dan RS Fatmawati Jakarta pada Juli hingga Desember 2018. Seluruh penderita keganasan ovarium dan penderita tumor jinak ovarium yang memenuhi kriteria diikutsertakan dalam penelitian ini. Darah penderita tumor ovarium diambil sebelum dilakukan operasi, lalu sampel dilakukan pengukuran kadar SOD dan MDA. Terdapat 35 penderita keganasan ovarium dan 43 penderita tumor jinak ovarium yang diikutsertakan dalam penelitian ini. Rerata atau median kadar SOD dan MDA pada penderita keganasan ovarium adalah 1,23 (0,24-5,709) dan 0,803 ± 0,316 , sementara rerata atau median kadar SOD dan MDA pada penderita tumor jinak ovarium adalah 0,488 (0,101-1,86) dan 0,634 ± 0,266. Terdapat perbedaan kadar SOD dan MDA yang bermakna antara kedua kelompok. Terdapat perbedaan kadar SOD yang bermakna antara penderita keganasan ovarium stadium awal dengan penderita keganasan ovarium stadium lanjut. Sementara pada pemeriksaan MDA tidak terdapat perbedaan bermakna antara penderita stadium awal dengan stadium lanjut. Kesimpullan pada penelitian ini terdapat perbedaan kadar SOD dan MDA yang bermakna antara penderita keganasan ovarium dengan penderita tumor jinak ovarium.

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Ovarian cancer is the leading cause of death due to gynecological malignancies among women. A lot of evidence shows that ovarian cancer is generally influenced by oxidative stress. In this study aims to determine the activity of SOD enzymes and MDA levels in patients with ovarian malignancies and patients with benign ovarian tumors. The study was conducted by cross-sectional tests carried out in the RSCM Jakarta Gynecology Obstetric Room and Persahabatan Hospital Jakarta and Fatmawati Hospital Jakarta in July to December 2018. All patients with ovarian malignancies and patients with benign ovarian tumors who met the criteria were included in this study. Blood from ovarian tumor patients taken before surgery, then the samples were measured for SOD and MDA levels. There were 35 ovarian malignancies and 43 patients with benign ovarian tumors included in the study. The mean or median level of SOD and MDA in patients with ovarian malignancy is 1.23 (0.24 - 5.709) and 0.803 ± 0.316, while the mean or median level of SOD and MDA in patients with benign ovarian tumors is 0.488 (0.101-1.86) and 0.634 ± 0.266. There were significant differences in SOD and MDA levels between the two groups. There were significant differences in SOD levels between patients with early-stage ovarian malignancies and those with advanced ovarian malignancies. While on MDA examination there were no significant differences between patients with early stages with advanced stages. Conclusion in this study were significant differences in SOD and MDA levels between ovarian malignancies and patients with benign ovarian tumors"

"Diagnosis kanker ovarium stadium lanjut memberikan kontribusi terbesar terhadap tingginya kasus kematian. Imunoterapi sebagai alternatif pengobatan diharapkan dapat mengobati pasien dengan kanker ovarium secara lebih cepat menggunakan sel imun bawaan yang dapat membunuh sel kanker secara permanen. Studi imunoterapi pada penelitian ini dilakukan dengan memanfaatkan interaksi antara ligan di dalam lingkungan mikro tumor dan reseptor sel NK. Reseptor NKP44 merupakan satu-satunya reseptor dengan dua mekanisme persinyalan berbeda yang secara aktif berperan penting dalam fungsi sel NK teraktivasi. Salah satu ligan potensial yang dapat meningkatkan fungsi pengenalan sel tumor melalui reseptor NKP44 adalah Nidogen-1 (NID1). Penelitian ini bertujuan untuk mengembangkan studi imunoterapi pasien dengan kanker ovarium serta mempelajari pengaruh interaksi ligan NID1 dengan reseptor NKP44 terhadap aktivitas sel NK. Metode penelitian yang dilakukan mencakup analisis ekspresi granul sitotoksik, analisis ekspresi NID1, uji keberhasilan ikatan ligan NID1 dengan sel NK, hingga analisis ekspresi NKP44. Hasil menunjukkan bahwa kelompok sel NK terinduksi memiliki aktivitas sitotoksik yang lebih baik dibandingkan kelompok sel NK tidak terinduksi melalui peningkatan ekspresi granul sitotoksik. Terdapat ekspresi NID1 meskipun dalam jumlah yang sedikit dan terkonfirmasi berhasil berikatan dengan sel NK. Namun, terjadi penurunan ekspresi NKP44 pada kelompok sel NK terinduksi sehingga perlu dilakukan analisis lanjutan penyebab penurunan ekspresi NKP44.

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Diagnosis of advanced ovarian cancer provides the largest contribution to the high number of deaths. Immunotherapy as an alternative treatment is expected to treat patients with ovarian cancer more quickly using innate immune cells that can permanently kill cancer cells. The development of immunotherapy in this study was carried out by utilizing the interaction between ligands in the tumor microenvironment and NK cell receptors. NKP44 is the only receptor with two different signaling mechanisms that actively play the most important role in the function of activated NK cells. One of the potential ligands that can improve tumor cell recognition function through the NKP44 receptor is Nidogen-1 (NID1). This research is aimed to develop immunotherapy studies for patients with ovarian cancer and to study the effect of the interaction of the NID1 ligand with the NKP44 receptor on NK cell activity. The research methods carried out included analysis of cytotoxic granule expression, analysis of NID1 expression, success test of NID1 ligand bonding with NK cells, and NKP44 expression analysis. The results showed that the induced NK cell group had better cytotoxic activity than the uninduced NK cell group through increased cytotoxic granule expression. There is expression of NID1 even in small numbers and it is confirmed that it binds successfully to NK cells. However, there was a decrease in the expression of NKP44 in the induced NK cell group so that further analysis needs to be carried out on the causes of the decrease in NKP44 expression."