Hubungan Ekspresi miR-21 dan miR-200c dengan Respons Terapi Sistemik Neoajuvan Pasien Kanker Payudara Stadium Lanjut

Abstract

Kegagalan terapi pada kanker payudara stadium lanjut dihubungkan dengan ekspresi mikroRNA antara lain miR-21 dan miR-200c. Untuk mengetahui hubungan respons terapi sistemik neoajuvan serta ekspresi miR-21 dan miR-200c pada pasien kanker payudara, dilakukan studi potong lintang di RS Kanker Dharmais dan RSUPN dr. Cipto Mangunkusumo (RSUPNCM) pada bulan Juli 2015 hingga April 2016. Subjek yang memiliki spesimen jaringan segar dan blok parafin serta telah mendapat pengobatan adekuat, dilakukan pengukuran MiR-21 dan miR-200c dengan qRT-PCR. Hasil dinyatakan sebagai perbedaan cycle thresholds (ΔCt) terhadap U6 snRNA. Ekspresi relatif dihitung sebagai perbedaan dua nilai ΔCt (ΔΔCt) dan fold change (2-ΔΔCt). Sebanyak 31 dari 60 subjek mendapat kemoterapi dan 29 mendapat terapi hormonal. Setelah terapi neoajuvan, hanya 46 orang subjek yang dapat menjalani mastektomi. Respons terapi dinilai dengan kriteria Miller Payne dari sediaan operasi. Sebanyak 23 (50%) subjek tidak respons (Miller Payne grade 1). ΔCt miR21 dan ΔCt miR-200c tidak berbeda bermakna pada subjek yang responsif dan tidak responsif, namun subjek yang tidak responsif memperlihatkan peningkatan ekspresi miR-200c (FC=2,375). Berdasarkan jenis terapi neoajuvan ekspresi miR21 maupun miR-200c lebih tinggi pada kelompok tidak respons dengan kemoterapi, sedang pada pemberian hormonal ekspresi miR-21 lebih rendah dan miR-200c cenderung lebih tinggi. Disimpulkan ekspresi miR-21 dan miR-200c tidak dapat digunakan untuk memprediksi respons terapi. Association of Expression of miR-21, miR-200c and response of Neoadjuvan Systemic Therapy in Patients with Breast Cancer  Treatment failure in advanced stage breast cancer has been associated with expression of microRNA e.g. miR-21 and miR-200c. To know the association between response neoadjuvant systemic therapy and the expressions of miR-21 and miR-200c in breast cancer patient, a cross-sectional study has been conducted in Dharmais Cancer Hospital and dr. Cipto Mangunkusumo Hospital National (CMHN) from July 2015 to April 2016. Patients had fresh and paraffin-embedded tissues from biopsy specimens and have been treated adequately. MiR-21 and miR-200c were measured using qRT-PCR on fresh tissues. Results were expressed as cycle thresholds difference (ΔCt) against U6 snRNA. Relative expression was calculated as difference of two ΔCt values (ΔΔCt) and fold change (2-ΔΔCt). Treatment response was evaluated histopathologically using Miller-Payne criteria on mastectomy specimens. A total of 60 patients were enrolled, 31 had chemotherapy and 29 had hormonal therapy. After treatment, only 46 patients were eligible for mastectomy. Twenty-three (50%) patients showed no response (Miller-Payne grade 1) after treatment. ΔCt miR-21 and ΔCt miR-200c were not significantly different between responsive and not responsive patients. However, patients with no response showed increased expression of miR-200c (FC=2.375). Based on type of neoadjuvant , in chemotherapy group expression of miR-21 and miR-200c were high(FC=3.67 and 6.16 respectively) but in hormonal group expression miR-21 FC=0.11 and miR-200c FC=1.25). In conclusion, expressions of miR-21 and miR-200c cannot be used to predict treatment response