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Abstrak :
Pendahuluan: Sindroma ovarium polikistik (SOPK) merupakan masalah reproduksi yang sering terjadi pada perempuan usia reproduksi, namun hingga saat ini etiopatogenesis SOPK masih belum jelas. Penelitian ini bertujuan menganalisis peran sel granulosa folikel ovarium dalam etiologi SOPK, keterkaitan genotip FSHR Asn680Ser dengan patogenesis SOPK dan peran gen CYP19A1(aromatase) dalam patogenesis SOPK. Metode: Penelitian ini menggunakan desain penelitian analitik observasional berbentuk studi seran lintang (cross sectional study) dan dilakukan di Departemen Biologi FKUI, Klinik Yasmin-RSCM Kencana dan Laboratorium terpadu FKUI pada tahun 2011-2014. Sebanyak 142 subyek penelitian (66 pasien SOPK dan 76 pasien bukan SOPK) terlibat dalam penelitian ini. Sampel penelitian berupa darah tepi dan cairan folikel ovarium yang diaspirasi ketika proses ovum pick up sebagai sumber sel granulosa. Dilakukan isolasi DNA untuk analisis RFLP polimorfisme FSHR Asn680Ser, dilakukan kultur sel granulosa untuk mengetahui kemampuan proliferasi sel granulosa dan analisis ekspresi mRNA aromatase sel granulosa dengan metode RT-qPCR. Hasil: Indeks proliferasi sel dan ekspresi mRNA aromatase sel granulosa pada kelompok SOPK lebih rendah secara bermakna dibandingkan bukan SOPK (p<0,05). Tidak ditemukan perbedaan bermakna distribusi genotip FSHR Asn680Ser antara kelompok SOPK dan bukan SOPK (p>0,05), tidak ditemukan perbedaan bermakna antara kadar hormon FSH basal berdasarkan variasi genotip FSHR Asn680Ser pada kelompok SOPK dan bukan SOPK (p>0,05). Tidak ditemukan perbedaan yang bermakna indeks proliferasi sel granulosa berdasarkan variasi genotip FSHR Asn680Ser baik pada kelompok SOPK maupun bukan SOPK (p>0,05). Tidak terdapat korelasi antara indeks proliferasi sel granulosa dengan ekspresi mRNA aromatase (p>0,05). Kesimpulan: Indeks proliferasi sel dan tingkat ekspresi mRNA aromatase sel granulosa kelompok SOPK menurun dibandingkan kelompok bukan SOPK. Genotip FSHR Asn680Ser tidak menentukan kerentanan individu untuk menderita SOPK. Kadar hormon FSH basal dan indeks proliferasi sel granulosa tidak berbeda antara kelompok SOPK dan bukan SOPK berdasarkan variasi genotip FSHR Asn680Ser. Tidak ada korelasi antara indeks proliferasi sel dengan ekspresi mRNA aromatase sel granulosa pada penelitian ini. ...... Introduction: Polycystic ovary syndrome (PCOS) is a common reproductive problem in women at reproductive age, but until now aetiopathogenesis of PCOS has not been fully understood. The objective of this study was to analyse interrelationship between proliferation of ovarian follicular granulosa cells, CYP19A1 expression and polymorphism at codon 680 of FSHR towards the etiology of PCOS. Methods: Observational analytic in the form of cross-sectional study was used in this research. The study was carried out between 2011-2014 at the Department of Biology, Integrated laboratory of Faculty of Medicine University of Indonesia and Yasmin clinic at the Cipto Mangunkusumo Hospital. A total of 142 subjects (66 patients with PCOS and 76 patients without PCOS) were involved in this study. Granulosa cells for culture were obtained from ovarian follicular fluid and total RNA was isolated from the cells. DNA samples were extracted from peripheral blood. Granulosa cell proliferation index was determined by counting under a phase-contrast microscope. CYP19A1 expression was measured by qRT-PCR, whereas polymorphism at Asn680Ser FSHR was performed by RFLP. Result: Cell proliferation index and CYP19A1 mRNA expression levels in the granulosa cells of the PCOS group was significantly lower than non-PCOS (p < 0.05). There was no significant difference found in Asn680Ser FSHR genotype distribution between PCOS and non-PCOS group (p > 0.05). Based on Asn680Ser FSHR genotype variation, no significant difference was found between basal FSH hormone levels in the PCOS and non- PCOS group (p > 0.05) and FSHR genotype variation did not correlate with granulosa cell proliferation index between PCOS and non-PCOS group (p > 0.05). Moreover, there was no correlation between the granulosa cell proliferation index with aromatase mRNA expression levels (p > 0.05). Conclusion: Cell proliferation index and CYPA1 expression of granulosa cells in PCOS group were lower compared to the non PCOS group although no correlation was found between the two parameters. Asn680Ser FSHR genotype did not correlate with individual susceptibility to PCOS. FSHR genotype variation did not correlate with basal FSH levels and granulosa cell proliferation index between PCOS and non-PCOS.

Abstrak :
Radiasi merupakan terapi pilihan untuk kanker serviks stadium III B, namun permasalahan timbul karena adanya sifat radioresisten. Sel punca kanker SPK merupakan salah satu faktor yang diduga berkontribusi terhadap hal tersebut. SOX2 dan OCT4 merupakan faktor transkripsi yang mengekspresikan sifat-sifat SPK, yaitu mengontrol sifat pluripoten, self-renewal, berperan pada karsinogenesis, metastasis, resistensi terhadap terapi dan rekurensi tumor. Faktor apoptosis, DNA repair dan telomerase merupakan mekanisme yang berkaitan dengan radioresisten. Penelitian ini bertujuan untuk mempelajari hubungan antara SOX2 dan OCT4 sebagai penanda SPK terhadap respons terapi radiasi, serta kaitannya dengan faktor apoptosis caspase-3 , DNA repair Chk1 dan telomerase hTERT .Penelitian ini merupakan case control, terhadap 48 kasus karsinoma sel skuamosa serviks stadium III B yang telah menjalani terapi radiasi/kemoradiasi di RS Cipto Mangunkusumo/FKUI. Kasus dibagi dalam 2 kelompok, yaitu hasil terapi komplet 27 kasus dan hasil terapi inkomplet 21 kasus . Kasus dengan respons awal terapi radiasi baik dilakukan pemeriksaan bulan Pap smear dan HPV pada bulan ke-6 atau sampai ke-12 setelah terapi. Ekspresi SOX2, OCT4, caspase-3, Chk1 dan hTERT diperiksa secara imunohistokimia dari blok parafin biopsi awal.Ekspresi kuat SOX2 dan OCT4 dengan H-score masing-masing lebih dari 96,6 dan 61,9 mempunyai hubungan bermakna dengan respons awal terapi radiasi maupun respons akhir terapi radiasi SOX2 p = 0,017, p = 0,004 dan OCT4 p < 0,001, p < 0,001 . Ditemukan hubungan bermakna antara ekspresi Chk1 dan hTERT dengan respons awal terapi radiasi Chk1 p = 0,006, hTERT p = 0,029 . Tidak ditemukan hubungan yang bermakna antara ekspresi caspase-3, Chk1, hTERT dengan ekspresi SOX2 dan OCT4. Uji multivariat menunjukkan bahwa SOX2 dan OCT4 yang paling memengaruhi respons terapi OR = 5,12, p = 0,040 dan OR = 17,03, p < 0,001, secara berurutan . Uji probabilitas menunjukkan kemungkinan respons akhir terapi radiasi inkomplet sebesar 87,91 bila ekspresi kedua penanda SPK kuat.Ekspresi kuat SOX2 dan OCT4 dapat memprediksi hasil terapi radiasi inkomplet pada karsinoma serviks stadium III B. ...... Radiotherapy is the main choice of treatment for stage III B cervical cancer, but radioresistance becomes a difficult matter. Cancer stem cell is one of the factors suspected involving in radioresistant cancers. SOX2 and OCT4 are transcription factors which have pluripotent cell characteristics, and self renewal ability. They also involved in carcinogenesis, metastasis, tumor recurrent, and resistance toward therapy. Apoptotic, DNA repair, and telomerase factors are mechanisms that also contribute to radioresistance. This study aims to know the role of SOX2 and OCT4 as CSC markers, apoptotic factor caspase 3 , DNA repair Chk1 and telomerase hTERT toward radiotherapy.The design of this study was case control with 48 cases of stage III B cervical squamous cell carcinoma patients who had finished receiving radiation chemo radiation therapy at Cipto Mangunkusumo Hospital FMUI, Jakarta. They were classified in 2 groups based on the final response of treatment, which were complete and incomplete one. Pap smear and DNA HPV were performed in month 6 or until month 12 after therapy for good initial therapy. Immunohistochemistry was done to analyze SOX2, OCT4, caspase 3, Chk1 and hTERT expression from the paraffin block of initial biopsy.Strong expression of SOX2 and OCT4 with each H score was higher than 96.6, and 61.9 had significant association with both initial and final therapy response SOX2 p 0.017, p 0.004 and OCT4 p 0.001, p 0.001, repectively . There was significant association between expression of Chk1 and hTERT, and initial therapy response p 0.006 for Chk1, and p 0.029 for hTERT . No significant differences were found between caspase 3, Chk1, hTERT, and SOX2 and OCT4. Multivariate analysis showed SOX2 and OCT4 were the most influenced antibodies for radiotherapy response OR 5.12, p 0.040, and OR 17.03, p 0.001, respectively . The likelihood of incomplete final therapy response was 87.91 if the expression both of CSC markers were strong.Expression of SOX2, and OCT4 could predict the incomplete radiotherapy of stage III B cervical cancer cases.