Ekspresi CD44 (Penanda Sel Punca Kanker) sebagai Faktor Prognostik Kekambuhan pada Kanker Ovarium Tipe Epitel Stadium III

PUNGKY MULAWARDHANA, INDRA YULIATI, KETUT SUDIANA

Abstract


Epithelial ovarian cancer is a deadly cancer, cancer recurrence and resistance post surgical staging and chemotherapy are major problems which will eventually occur in most advanced stage ovarian cancer. Recent investigations have unravelled the role of CSC/ Cancer Stem Cell in the cancer recurrence and therapy resistance, CD44 has been reported as a CSC marker in ovarian cancer, investigator wanted to analyse CD44 expression as recurrence prognostic factor in stage III epithelial ovarian cancer. Purpose: to analyse the role of CD44 expression as recurrence prognostic factor in stage III epithelial ovarian cancer. Metode: Hystorical Cohort, ICH CD44 examination was performed on the pathological ovarian cancer sample which diagnosed with platinum resistant recurrence (study sample) and platinum sensitive recurrence (control sample). CD44 expression was measured, the role as recurrence prognostic factor evaluated, influence of CD44 expression increase
towards earlier recurrence analysed, and the CD44 expression differences between 2 groups based on grade; pathological type; and stadium were measured and analysed. Results: 40 research subjects were involved in the research, with 20 among them were platinum resistant and the other 20 were platinum sensitive. Mean CD44 expression in the platinum resistant group was 36,80+29,54; while in the resistant platinum was 7,05+9,58. There was a significant difference of CD44 expression between 2 groups (p=0,000). There was a strong correlation between CD44 expression with the timing of recurrence (p=0,894). With the cut off of
12,5; 85% platinum resistant subject had CD44>12,5; 85% platinum sensitive subject had CD44<12,5; with 85% sensitivity and 85% specificity as a good recurrence prognostic factor. Relative Risk (RR) of CD44 Expression is 5,667, RR
of tumor residue post surgical staging is 2,513. Through logistic regression analysis, it was concluded that high expression of CD44 and tumor residue are risk factors for recurrences, patient with CD44 expression of ≥ 12,50 has possibility of earlier recurrence (< 6 months) 48,487 times compared with patient with CD44 expression of < 12,50 and patient with tumor residue of < 1cm has possibility of earlier recurrence 13,013 times compared with patient without macroscopic residue.
Conclusion: This research found that CD44 expression can be used as recurrence prognostic factor in stage III epithelial ovarian cancer, CD44 expression was significantly higher in the platinum resistant group, there was negative correlation
between CD44 expression with the timing of recurrence. CD44 expression as recurrence prognostic factor was not influenced with grade and pathologic type, but influenced by stage. Expression of CD44 and tumor residue post surgical staging are good predictors for recurrence timing.

ABSTRAK
Kanker ovarium tipe epitel adalah suatu kanker yang mematikan. Kekambuhan dan resistansi kanker pasca-surgical staging dan kemoterapi merupakan masalah utama yang akan terjadi pada sebagian besar kanker ovarium stadium  lanjut. Penelitian-penelitian terbaru mengemukakan peran CSC (Cancer Stem Cell) dalam proses kekambuhan dan resistansi terapi. CD44 telah dilaporkan sebagai marker CSC pada kanker ovarium. Peneliti ingin meneliti ekspresi CD44 sebagai faktor prognostik kekambuhan kanker ovarium tipe epitel stadium III. Penelitian ini bertujuan menganalisis peran ekspresi CD44 sebagai faktor prognostik kekambuhan pada kanker ovarium tipe epitel stadium III. Metode yang digunakan dalam penelitian ini adalah hystorical cohort, di mana dilakukan pemeriksaan IHC CD44 pada sampel PA pasien kanker ovarium yang mengalami kekambuhan resistan platinum (sampel studi) dan sensitif platinum (sampel pembanding). Ekspresi CD44 diukur, peran sebagai faktor prognostik kekambuhan dievaluasi, pengaruh peningkatan ekspresi CD44 pada kekambuhan yang lebih dini dianalisis, dan perbedaan ekspresi CD44 dinilai pada 2 kelompok berdasarkan grade, tipe PA, dan stadium. Sebanyak 40 subjek penelitian dengan rincian 20 kelompok resistan platinum dan 20 kelompok sensitif platinum diikutkan dalam penelitian ini. Rerata ekspresi CD44 pada kelompok resistan adalah 36,80+29,54 dan kelompok sensitif platinum 7,05+9,58. Didapatkan perbedaan signifikan ekspresi CD44 di antara dua kelompok (p=0,000). Didapatkan pula hubungan yang kuat antara ekspresi CD44 dengan waktu kekambuhan (p=0,894). Dengan cut off 12,5; 85% sampel resistan platinum memiliki CD44>12,5 dan 85% sampel sensitif platinum memiliki CD44<12,5 dengan sensitivitas 85% dan spesifisitas 85% sebagai faktor prognostik kekambuhan yang baik. Didapatkan RR ekspresi CD44 sebesar 5,667, RR residu tumor pasca-surgical staging sebesar 2,513. Melalui analisis regresi logistik, didapatkan bahwa ekspresi CD44 yang tinggi dan adanya residu merupakan faktor risiko kekambuhan. Penderita dengan ekspresi CD44 ≥ 12,50 berisiko kambuh <6 bulan sebesar 48,487 kali penderita dengan ekspresi CD44 < 12,50; dan penderita dengan residu < 1 cm berisiko kambuh <6 bulan sebesar 13,013 kali penderita tanpa residu makroskopik. Penelitian ini menyimpulkan bahwa ekspresi CD44 dapat dipakai sebagai faktor prognostik kekambuhan pada kanker ovarium tipe epitel stadium III, ekspresi CD44 secara signifikan lebih tinggi pada kelompok resistan platinum, serta ada hubungan negatif antara ekspresi CD44 dengan waktu terjadinya kekambuhan. Ekspresi CD44 sebagai faktor prognostik tidak dipengaruhi oleh grade dan tipe PA, tetapi dipengaruhi oleh stadium kanker. Ekspresi CD44 dan residu tumor pasca-surgical staging merupakan indikator prediktif yang baik untuk kecepatan kekambuhan.


Keywords


stage III epithelial ovarian cancer, CSC, CD44, platinum sensitive, platinum resistance, recurrence prognostic factor, IHC, grade, pathologic type, stage

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DOI: 10.14414/ijoc.v11i3.516

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