Tesis

Gambaran Ekspresi Protein P16 dan P21 dalam Hubungan Cellular Senescence pada Kanker Ovarium Tipe Epitelial di RSUPN Cipto Mangunkusumo = Expression Profile of P16 and P21 Proteins in Relation to Cellular Senescence in Epithelial-Type Ovarian Cancer at Cipto Mangunkusumo National General Hospital.

Latar Belakang: Kanker ovarium merupakan salah satu penyebab utama kematian akibat kanker ginekologi, di mana sekitar 70% kasus terdiagnosis pada stadium lanjut dan memiliki angka kekambuhan tinggi meskipun telah menjalani terapi optimal. Cellular senescence menjadi mekanisme penting dalam menekan progresivitas tumor melalui penghentian siklus sel secara permanen, dengan protein P16 dan P21 sebagai marker utama. Namun, data mengenai pola ekspresi dan relevansi prognostik kedua protein ini pada kanker ovarium tipe epitelial di populasi Indonesia masih terbatas. Metode: Penelitian potong lintang ini menggunakan 17 sampel jaringan kanker ovarium tipe epitelial dari pasien yang menjalani operasi primer tanpa kemoterapi sebelumnya di RSUPN Cipto Mangunkusumo. Pemeriksaan imunohistokimia dilakukan untuk menilai ekspresi nuklir P16 dan P21 yang dikategorikan menjadi negatif, fokal/lemah, atau positif kuat. Hubungan antara ekspresi protein dan stadium FIGO dianalisis menggunakan uji chi-square dengan nilai p < 0,05 sebagai batas signifikansi. Hasil: Sebagian besar sampel berada pada stadium I (47,1%) dan stadium IV (23,5%). Ekspresi berlebih P16 teridentifikasi pada 47,1% sampel, sedangkan P21 positif ditemukan pada 13 sampel. Ekspresi P16 cenderung lebih tinggi pada stadium lanjut (III–IV), dan P21 positif lemah lebih sering ditemukan pada stadium IV. Namun demikian, tidak terdapat hubungan bermakna antara P16 (p = 0,504) maupun P21 (p = 0,504) dengan stadium kanker. Analisis odds ratio menunjukkan kecenderungan peningkatan risiko stadium lanjut pada ekspresi berlebih P16 (OR 5,00) dan ekspresi P21 lemah (OR 5,00), meskipun interval kepercayaan yang lebar mencerminkan keterbatasan jumlah sampel. Kesimpulan: ekspresi P16 dan P21 cenderung meningkat pada kanker ovarium stadium lanjut, keduanya belum menunjukkan hubungan prognostik yang signifikan dan belum dapat digunakan sebagai indikator independen pada kanker ovarium tipe epitelial.
Kata Kunci: Kanker ovarium epitelial, cellular senescence, P16, P21, prognostik


Background: Ovarian cancer remains one of the deadliest gynecologic malignancies, with approximately 70% of cases diagnosed at advanced stages and a high recurrence rate despite optimal treatment. Cellular senescence has emerged as a crucial tumor-suppressive mechanism through irreversible cell-cycle arrest, in which P16 and P21 act as key regulatory markers. However, data regarding their expression patterns and prognostic relevance in epithelial ovarian cancer in the Indonesian population remain limited. Methods: A cross-sectional study was conducted using 17 epithelial ovarian cancer tissue samples obtained from patients who underwent primary tumor resection without prior chemotherapy at Cipto Mangunkusumo National General Hospital. Immunohistochemistry was performed to evaluate nuclear expression of P16 and P21, categorized into negative, focal/weak, and strong overexpression. The association between protein expression and FIGO stage was analyzed using chisquare testing, with p < 0.05 considered statistically significant. Results: Most subjects were classified as FIGO stage I (47.1%) and stage IV (23.5%). P16 overexpression was identified in 8 samples (47.1%), while P21 positivity (weak or strong) was observed in 13 samples. P16 overexpression tended to be more prevalent in advanced stages (III–IV), and weak P21 expression was more frequently observed in stage IV compared with earlier stages. Nonetheless, neither P16 expression (p = 0.504) nor P21 expression (p = 0.504) demonstrated a statistically significant association with cancer stage. Odds ratio analysis indicated a trend toward increased risk of advanced-stage disease in cases with P16 overexpression (OR 5.00) and weak P21 expression (OR 5.00), although wide confidence intervals reflected imprecision due to small sample size. Conclusion: P16 and P21 expression tends to be higher in advanced-stage ovarian cancer but shows no significant association with cancer stage. These proteins may serve as potential biomarkers of cellular senescence but cannot yet be considered independent prognostic factors in epithelial ovarian cancer.
Keywords: Epithelial ovarian cancer, cellular senescence, P16, P21, prognosis