Ekspresi CTR1 dan ATP7B sebagai Prediktor Respons Kemoterapi Neoadjuvan Cisplatin pada Kanker Serviks IIB

PUTU AGUS SUARTA* -  , Indonesia

DOI : 10.33371/ijoc.v9i2.378

The locally advanced cervical cancer is common in Indonesia and with limitation of radiation, chemotherapy is used as a neoadjuvant treatment. However the clear mechanism of accumulation chemotherapy in cervical cancer is still unclear. The purpose this study to determine CTR1 and ATP7B expression as a predictor of response to neoadjuvant chemotherapy cisplatin in cervical cancer IIB The design of this research is observational analytic form prospectively on 30 sample cervical cancer stage IIB. Before chemotherapy, Cervical biopsy was taken to evaluate expression CTR1 and ATP7B and MRI was done to measure the tumor volume. Furthermore, four cycles neoadjuvat chemotherapy (NAC) cisplatin 50mg/m2 every weeks. Two - three weeks after complete chemotherapy, repeated MRI examination. Assessment response to chemotherapy was catagorized by RECIST. Results: 30 samples obtained from the study of cervical cancer, before chemotherapy the smallest volume 23.35 cm3 and the greatest 276.23 cm3. After chemotherapy smallest 2.14 cm3 and largest 422.11 cm3. Chemotherapy response obtained Partial Response (PR) 23 (76.7%), Stable Disease (SD) 5 (16.6%), Progressive Disease (PD) 2 (6.7%). Relationship CTR 1 expression and response to chemotherapy according to RECIST obtained p value 0.002. Relationship ATP7B expression and chemotherapy response according to RECIST obtained with p value 0.009. In multiple logistic regression analysis obtained CTR 1 with p 0.006 and p value 0.454 ATP7B. Conclusions: CTR1 and ATP7B expression can be used as a predictor of response to chemotherapy neoadjuvant cisplatin in cervical cancer IIB, CTR expression more better as a predictor of response to neoadjuvant chemotherapy.Keyword: Neoadjuvant chemotherapy, MRI, Cisplatin, RECIST, CTR1 ATP7BABSTRAKKanker serviks lokal lanjut masih menjadi masalah umum di Indonesia. Dengan keterbatasan radiasi maka kemoterapi sebagai neoadjuvan dipakai sebagai alternatif pengobatan. Mekanisme pasti akumulasi obat kemoterapi masih belum jelas. Penelitian ini bertujuan untuk mengetahui ekspresi CTR1 dan ATP7B sebagai prediktor respons terhadap kemoterapi cisplatin pada kanker serviks IIB. Rancangan penelitan ini adalah analitik observasional dengan bentuk prospektif. Dari 30 sampel penelitian kanker serviks IIB, dilakukan pemeriksaan MRI untuk mengukur volume serviks dan parametrium serta biopsi serviks untuk dilakukan pemeriksaan IHC (immunochemistry) CTR1 dan ATP7B. Selanjutnya diberikan Neoadjuvat chemotherapy (NAC) cisplatin 50 mg/m2 tiap minggu 4 kali. Setelah 23 minggu setelah NAC dilakukan pemeriksaan MRI ulangan. Penilaian respons kemoterapi dilakukan dengan RECIST. Hasil penelitian menunjukkan dari 30 sampel penelitian sebelum kemoterapi, volume serviks dan parametrium terkecil 23,35 cm3 dan terbesar 276,23 cm3. Setelah kemoterapi, terkecil 2,14 cm3 dan terbesar 422,11 cm3. Respons kemoterapi didapatkan Partial Response (PR) 23 (76.7%), Stable Disease (SD) 5 (16.6%), Progressive Disease (PD) 2 (6.7%). Hubungan ekspresi CTR 1 dan respons kemoterapi sesuai RECIST didapatkan dengan nilai p 0,002. Hubungan ekspresi ATP7B dan respons kemoterapi sesuai RECIST didapatkan dengan nilai p 0,009. Pada analisis regresi logistik ganda didapatkan CTR 1 dengan nilai p 0,006 dan ATP7B nilai p 0,454. Penelitian ini menyimpulkan bahwa ekspresi CTR1 dan ATP7B dapat dijadikan sebagai prediktor respons Neoadjuvant chemotherapy cisplatin pada kanker serviks IIB. Bila dibandingkan, ekspresi CTR 1 lebih baik sebagai prediktor respons kemoterapi neoadjuvant.Kata kunci: Neoadjuvant chemotherapy, MRI, cisplatin, RECIST, CTR1 ATP7B
Keywords
Neoadjuvant chemotherapy; MRI; Cisplatin; RECIST; CTR1 ATP7B
  1. Arbyn M, Castellsague X, de Sanjose S, Bruni L, Saraiya M, Bray F, et al. Worldwide burden of cervical cancer in 2008. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO. 2011;22(12):2675-86.
  2. Aziz MF. Gynecological cancer in Indonesia. Journal of Gynecologic Oncology. 2009;20(1):8-10.
  3. Askandar B, Santoso C. The effectiveness of neodjuvant chemotherapy in cervical cancer stage IIB. Gynecologic Oncology. 120:S114.
  4. Tambaro R, Scambia G, Di Maio M, Pisano C, Barletta E, Iaffaioli VR, et al. The role of chemotherapy in locally advanced, metastatic and recurrent cervical cancer. Critical Reviews in Oncology/Hematology. 2004;52(1):33-44.
  5. Kim ES, Tang X, Peterson DR, Kilari D, Chow CW, Fujimoto J, et al. Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer. Lung Cancer 2014;85(1):88-93.
  6. Stewart DJ. Mechanisms of resistance to cisplatin and carboplatin. Critical Reviews In Oncology/Hematology 2007;63(1):12-31.
  7. Nakayama K, Kanzaki A, Ogawa K, Miyazaki K, Neamati N, Takebayashi Y. Copper-transporting P-type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian carcinoma: comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP. International Journal of Cancer Journal International du Cancer. 2002;101(5):488-95
  8. Nuranna L. Distribution of Age, Stage, and Histopathology of Cervical Cancer: A Retrospective Study on Patients at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia, 2006-2010. Indones J Obstet Gynecol. 2011;35:21-4.
  9. Parazzini F, La Vecchia C, Negri E, Cecchetti G, Fedele L. Reproductive factors and the risk of invasive and intraepithelial cervical neoplasia. British Journal of Cancer. 1989;59(5):805-9.
  10. Kim ES, Lee JJ, He G, Chow C-W, Fujimoto J, Kalhor N, et al. Tissue Platinum Concentration and Tumor Response in NonSmall-Cell Lung Cancer. Journal of Clinical Oncology 2012;30(27):3345-52.
  11. Lee Y-Y, Choi CH, Do I-G, Song SY, Lee W, Park HS, et al. Prognostic value of the copper transporters, CTR1 and CTR2, in patients with ovarian carcinoma receiving platinum-based chemotherapy. Gynecologic Oncology 2011;122(2):361-5.
  12. Sugeno H, Takebayashi Y, Higashimoto M, Ogura Y, Shibukawa G, Kanzaki A, et al. Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) in human hepatocellular carcinoma. Anticancer Research 2004;24(2c):1045-8.
  13. Katagiri H, Nakayama K, Rahman MT, Rahman M, Katagiri A, Ishibashi T, et al. Is ATP7B a predictive marker in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy? International Journal of Gynecological Cancer : Official Journal of The International Gynecological Cancer Society 2013;23(1):60-4.
  14. Miyashita H, Nitta Y, Mori S, Kanzaki A, Nakayama K, Terada K, et al. Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a chemoresistance marker in human oral squamous cell carcinoma treated with cisplatin. Oral Oncology 2003;39(2):157-62.
  15. Chen HHW, Yan J-J, Chen W-C, Kuo MT, Lai Y-H, Lai W-W, et al. Predictive and prognostic value of human copper transporter 1 (hCtr1) in patients with stage III non-small-cell lung cancer receiving first-line platinum-based doublet chemotherapy. Lung Cancer (Amsterdam, Netherlands). 2012;75(2):228-34.
  16. Song IS, Savaraj N, Siddik ZH, Liu P, Wei Y, Wu CJ, et al. Role of human copper transporter Ctr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant cells. Molecular Cancer Therapeutics 2004;3(12):1543-9.

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Submitted: 2015-09-23
Published: 2015-07-01
Section: Research Articles
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